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Evaluation and Outcomes of Patients With Palpitations
Barbara E. Weber, MD, MPH, Rochester, New York, Wishwa N. Kapoor, MD, MPH, Pittsburgh, Pemsy/vania
PURPOSE:
To determine: (1) the etiologies of pal-
pitations, (2) the usefulness of diagnostic tests in
determining the etiologies o f palpitations, and (3)
the outcomes of patients with palpitations.
PAIIENTS AND
METHODS:ne hundred and ninety
consecutive patients presenting with a complaint
of palpitations at a university medical center were
enrolled in this prospective cohort study. Patients
undement a structured clinical interview and psy-
chiatric screening. The charts were abstracted for
results of the physical exam and tests ordered by
the primary physician. Assignment of an etiology
of palpitations was based on strict adherence to
predetermined criteria and achieved by consensus
of the two physician investigators. One-year follow-
up was obtained in 96% of the patients.
RESULTS
An etiology of palpitations was deter-
mined in 84% of the patients. The etiology of pal-
pitations was cardiac in 43%, psychiatric in 31%,
miscellaneous in lo%, and unknown in 16%. Forty
percent of the etiologies could be determined with
the history and physical examination, an electro-
cardiogram, and/or laboratory data. The l-year
mortality rate was 1.6% (95% confidence interval
[Cl] 0% to 3.4%) and the l-year stroke rate was
1.1% (95% Cl 0% to 2.6%). W&in the first year,
75% of the patients experienced recurrent palpita-
tions. At l-year follow-up, 89% reported that their
health was the same or improved compared to
that at enrollment, 19% reported that their work
performance was impaired, 12% reported that
workdays were missed, and 33% repotted accom-
plishing less than usual work at home.
CONCLUSIONS: The etiology o f palpitations can of-
ten be diagnosed with a simple initial evaluation.
Psychiatric illness accounts for the etiology in
nearly one third of all patients. The short-term
prognosis of patients with palpitations is excellent
with low rates of death and stroke at 1 year, but
From the Universitv of Prttsburah School of Medicine (WNK),University
of Pittsburgh Medical Center, Pi&burgh, Pennsylvania,and the University
of Rochester, School of Medicine and Dentistry (BEW),St. Mary’s
Hosoltal. Rochester. New York.
D;. Wikhwa N. Kapoor is a recipient of a Research Career Development
Award from the National Heart, Lung, and Blood Institute (K04L 01899).
Requests or reprints should be addressed to Barbara E. Weber, MD,
MPH, St. Mary’s Hospital. 89 Genesee Street, Rochester, New York
14611.
Manuscript submitted December 29, 1994 and accepted in revised
form July 10, 1995.
there is a high rate of recurrence of symptoms
and a moderate impact on productivity.
P
alpitations are one of the most common symp-
toms in general medical settings, reported by as
many as 16% of the patients.’ This symptom may be
caused by a variety of disorders, ranging from life-
threatening conditions such as ventricular tachycar-
dia2 to various psychiatric illnesses.3 As a result, pa-
tients with palpitations often undergo a wide variety
of diagnostic tests and referrals leading to substan-
tial resource utilization.* Currently, clinical experi-
ence guides the physician caring for patients with pal-
pitations, since there are no prior studies that
describe the spectrum of etiologies or the usefulness
of diagnostic tests in the evaluation of palpitations.
Furthermore, the outcome of patients with palpita-
tions has not been well described. In the only re tro-
spective study of outcomes in patients with palpita-
tionq5 cases with palpitations and controls without
palpitations experienced similar rates of cardiac end-
points. The purpose of this prospective study was to
determine (1) the etiologies of palpitations, (2) the
usefulness of diagnostic tests in determining the eti-
ologies of palpitations, and (3) the outcomes of pa-
tients with palpitations.
PATIENTS AND METHODS
This was a prospective cohort study of patients pre-
senting with palpitations. Palpitations were defined
as one or more of the following patient complain ts:
fast heart beats, skipped heart beats, irregular heart
rate, and heart fluttering, racing, o r pounding.”
Study Entry Criteria
Between January 2 and August 30, 1 391, all pa-
tients presenting to the emergency department, ad-
mitted to the medica l and surgical inpatient service,
or attending the medica l clinics of the University of
Pittsburgh Medical Center were screened for study
eligibility. Patients presenting to the psychiatric
emergency department or admitted directly to the
psychiatric service were not screened far study eli-
gibility. Inclusion criteria were palpitations as a chief
complaint for seeking medical care or palpitations as
one of the chief complaints during a routine visit to
the physician. The symptom must have occurred at
least once in the 3 months preceding this index visit.
Patients were excluded if their age was less than 18
years, they were known to be aphasic or demented,
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PATlEriTS WITH PALPITATiONS/WEBER AND KAPOOR
or were unable to speak English. Patients transferred
from the inpatient service of another hospital, those
admitted only for same-day surgery, and patients
with palpitations only elicited on review of systems
were also excluded.
Patient Identification
Because palpitations are often not the sole diag-
nosis for admission or discharge, and patients with
palpitations are often labeled with a more specific d i-
agnosis, a comprehensive search strategy was used
to capture all patients with palpitations. To identify
patients eligible for the study, we performed daily re-
view o f the following lists: emergency department dis-
charge diagnoses, hospital admission diagnoses, and
outpatient visit discharge diagnoses. If any of the di-
agnoses noted in Table I was found, the medical
chart was reviewed and the patient’s physician was
contacted to ascertain if the chief complaint was pal-
pitations. In cases in which this could not be ascer-
tained, the patient was contacted for clarification.
Patients who met the entry criteria were asked to par-
ticipate in the study. Conduct of the study was ap-
proved by the institutional review board of the
University of Pittsburgh.
Patient Evaluation
Patients who agreed to participate were inter-
viewed. The structured interview was directed at the
following issues: palpitation
characteristics,
associ-
ated symptoms and situations, drug and medication
use, and comorbid illness. Medical
charts
were re-
viewed and data were abstracted regarding physical
examination findings and results of the diagnostic
evaluation. This process was completed by the prin-
cipal investigator (BEW) as soon as possible after the
patient presented for medical care. Interviews were
performed in person with 42%and on the phone with
58%of patients. The mean time in days between event
and evaluation was 1.1, evaluation and interview was
3.4, and event and interview was 4.2. The median time
in days between event and evaluation was 0, evalua-
tion and interview was 2, and
event
and interview was
2. The physical exam and diagnostic evaluation (ie,
electrocardiogram [ECG], laboratory tests, arrhyLh-
mia detection) was determined by the individual
physician seeing the patient at the index visit. In cases
in which tests for arrhythmia detection were not or-
dered by the clinician, the investigators made loop
monitors available.
To screen for generalized anxiety disorder, panic at-
tack, panic disorder, major depression, and somatiza-
tion disorder, patients were asked to complete two val-
idated self-administered instruments: the
General
Health Questionnaire (GHQ),7-12 nd the somatization
screening test of Othmer and DeSouza13 SOM). The
TABLE I
Diagnoses Used to Identify Patients
Anemia
Transfusion
Anxiety
Aortic aneurysm
Arrhythmia
Specific arrhythmias (ie, atrial fibrillation, atrial flutter, brady-
cardia, multifocal atrial tachycardia, pre-excitation syndrome,
sick sinus syndrome, supraventricular tachycardia, ventricular
tachycardia, ventricular fibrillation)
Atrial myxoma
Cardiomyopathy
Chest pain
Cocaine abuse
Congestive heart failure
Dizziness
Drug toxicity (ie, amphetamines, theophylline)
High output failure
Hypoglycemia
Pacemaker failure
Palpitations
Panic attack
Pheochromocytoma
Rule out myocardial infarction
Shunt or fistula (peripheral or cardiac)
Syncope
Thyrotoxicosis
Unstable angina
Valvular heart disease
30question GHQ was answered using a 4 point Likert
scale and scored with 1 point for each response of 3
or 4, allowing for a maximum score of 30. The 7ques
tion SOM was scored with 1 point for each positive re
sponse. Patients with a GHQ score14J5 f 25 or a SOM
score16of 23 or in whom these psychiatric illnesses
were clinically suspected were further assessedwith
the Diagnostic Interview Schedule (DIS)17Js ections
for generalized anxiety disorder, panic attack and dis-
order, major depression, and/or somatization disorder.
The DIS was adininistered over the telephonelg by a
trained certified registered nurse practitioner. The
Diagnostic and Statistical Manual of Mental Disorders,
third edition revised, (DSM-III-R>2Oriteria were used
to score the DIS. Generalized anxiety disorder, panic
attack and disorder, and somatization disorder were
considered present if symptoms were present within
the last 6 months. Depression was evaluated as a life-
time disorder. Depression was considered to be C(F
morbid and not etiologic, since palpitations are not
listed as a criterion symptom in DSM-III-R.
Assignment of Etiology of Palpitations
Diagnostic criteria for the etiology of palpitations
were developed prior to the start of the study after
extensive review of the literature (see Appendix).
We appraised pertinent articles, case reports, review
papers, and cardiology and general medicine text-
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TABLE II
Patient Characteristics (N = 190)’
Mean age (yl
46
Range 18-87
Female 61
White
74
21 year of college education 57
Site of presentation
Emergency department 62
Medical clinic 28
Symptom presentation
Chief complaint 87
Complaint during a routine visit
13
Admitted to hospital 35
History of prior palpitations 77
History of
Heart disease+ 32
Hypertension 29
Congestive heart failure 13
Diabetes mellitus
7
‘Other than mean age, data shown represent the percentage of patients
included.
‘Coronary (ie, history of myocardial infarction, angina, coronary artery by-
pass grafting, percutaneous transluminal coronary angioplas ty), congen-
ital, or valvular heart disease, or cardiomyopathy.
books to find disorders associated with the symptom
of palpitations. Assignment of an etiology was based
on strict adherence to these criteria and achieved by
consensus of the two physician investigators.
The diagnostic criteria permitted a simple catego-
rization of the etiologies of palpitations. Cardiac eti-
ology included arrhythmias, cardiac and extra-car-
diac shunts, regurgitant vahular heart disease,
pacemaker, prosthetic heart valve, cardiomegaly, mi-
tral valve prolapse, hyperkinetic heart syndrome, and
atrial myxoma. Psychiatric etiology included panic at-
tack, panic disorder, generalized anxiety disorder,
and somatization disorder. The category of miscella-
neous etiology included medications, habits, meta-
bolic disorders, high output states, dehydration and
orthostatic hypotension, and exertion.
Given the available information (ie, history, physi-
cal, diagnostic evaluation, psychiatric testing), the in-
vestigators considered each etiology (see Appendix).
Because correlation of symptoms with documented
arrhythmias was the most concrete example of
causality, whenever this occurred the diagnosis of ar-
rhythmia was assigned. The remaining etiologies
were carefully considered for their presence or ab-
sence. This hierarchy always designated cardiac ar-
rhythmias as the etiology, although psychiatric or
metabolic comorbid conditions may have been pre-
sent. Similarly, metabolic disorders were considered
to be the etiology, although psychiatric conditions
may have been present.
These diagnoses were considered definite, with only
three exceptions. Diagnoses involving medications or
TABLE Ill
Etiologies of Palpitations
No. Percent
Cardiac
82 43.2
Atrial fibrillation
19
10.0
Supraventricular tachycardia
18
9.5
Premature ventricular beats 15 7.9
Atrial flutter
11
5.8
Premature atrial beats
6
3.2
Ventricular tachycardia 4
2.1
Mitral valve prolapse 2
1.1
Sick sinus syndrome 2
1.1
Pacemaker failure 2
1.1
Aortic insufficiency 2
1.1
Atrial myxoma 1
0.5
Psychiatric
58 30.5
Panic attack or disorder plus anxiety 20
10.5
Panic attack alone 17
8.9
Panic disorder alone 14
7.4
Anxiety alone 6
3.2
Panic plus anxiety plus somatization 1
0.5
Miscellaneous 19
10.0
Medication 5
2.6
Thyrotoxicosis 5 2.6
Caffeine 3
1.6
Cocaine
2 1.1
Anemia
2
1.1
Amphetamine 1
0.5
Mastocytosis
1
0.5
Unknown 31 16.3
habits were considered to be definite, probatble, or pos-
sible, adapted from the literature on adverse drug ef-
fects.*l Arrhythmias (only supraventricular tihycar-
dia and ventricular tachycardia) and anxiety were
considered definite or probable. Only 5.8%of the pa-
tients had etiologies that were considered probable or
possible. As this is the first study to explore the eti-
ologies for the symptom of palpitations, our focus was
on the spectrum of etiologies; therefore, for the analy-
ses presented here, the categories of definite, proba-
ble, and possible were combined. These
diamostic cri-
teria allowed patients to be assigned to only one
etiology category, but could have more than one diag-
nosis within that category (ie, premature ventricular
contraction and premature atrial contraction, cocaine
and caffeine, but not supraventricular tachycardia and
anxiety).
Follow-Up
All patients were contacted by phone at 3 and 6
months, and for final follow-up at 9 and/or 12 months.
Responses to standard questions regarding recur-
rences, new cardiovascular events, and mortality
were obtained from the patient, the family, or care-
giver; interviewers were trained to avoid leading ques-
tions and to be specific with respect to morbidity re-
lated only to palpitations. All interviews were
completed by October 28, 1992; over 90% of inter-
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PATIENTS WITH PALPITATlONS/WEBER AND KAPOOR
TABLE N
Selected Significant Variables and Their Relationship to Etiology’
Cardiac
Psychiatric Miscellaneous Unknown
Demographic
Mean (y)
ge
50 41 46 47
Male sex (%I 51 29 26 32
White (%)
85 67 74 58
Comorbidity
History of heart disease (%I
45
19 16
32
Symptom characteristics
Irregular heart beat (%)
34 21 50
Duration >5 minutes (%I :: 51 67 50
Total number of symptoms @I -131 3.5
5.3 4.3 2.9
'P do.05 (analysis of variance for age and number of symptoms and Fisher’s exact test for categorical variables).
One or more of the etiology categories is different from the others.
views were performed by the same physician’s assis-
tant. Whenever follow-up events occurred, attempts
were made to obtain further details from the primary
physician and medical chart. The cause of death was
assigned on the basis of information obtained from
the patient’s family and the medical chart.
Statistical Analyses
Standardized forms for entry of clinical, laboratory,
and outcome data were utilized. Data management and
analyses were conducted with the use of RBase
(Microrim Inc, Seattle, Washington),22 BMDP (UC
Press, Berkeley, California),23 StatXact (Cytel Corp,
Cambridge, Massachusetts),24 nd ROCFIT (University
of Chicago, Chicago, Illin~is)~~ software packages.
Statistical tests included the &i-square, Fisher’s exact,
and analysis of variance tests to evaluate differences
between groups. Logistic regression analysis (BMDP
LRa) was used to test for independence among pre-
dictors of a cardiac etiology of palpitations. Our intent
was to create a clinical prediction model that incor-
porated variables readily available in the initial history.
All variables tested were dichotomous, including the
composite variable ‘history of heart disease’, which
was considered present if any of the following was pre-
sent: histow of angina, myocardial infarction, cardiac
surgery, percutaneous lxansluminal coronary angio-
plasty, pulmonary hypertension, congestive heart fail-
ure, and va,lvular or congenital d isease.To evaluate this
prediction model, a receiver-operatingxharacteristic
(ROC) curve25was constructed based on the number
of multivariate predictors of cardiac etiology present.
One-year mortality and stroke rates were calculated
using the Kaplan-Meier method.26
RESULTS
Entry criteria were met by 229 patients. Thirty-nine
patients were not enrolled due to patient or physician
refusal. Therefore, 83% agreed to participate. Those
agreeing to participate did not d iffer in age, race, or
gender from those who refused. Selected features of
the 190 enrolled patients are shown in Ttible Il.
Etiologies
An etiology for palpitations was assigned in 159
[84%) patients. The specific etiologies are listed in
Table III.
Overall, 43% of the patients
had1
a cardiac
etiology, 31%had a psychiatric etiology, 10%had mis-
cellaneous etiologies, and 16%were unknown. For the
subgroup of patients presenting to the medical clinic,
the etiology was cardiac in Zl%, psychiatric in 45%,
miscellaneous
in 696,and 28%
unhewn. For the sub-
group of patients presenting to the emergency de-
partment, the etiology was cardiac in 47%,psychiatric
in 27%, miscellaneous in 13%, and 13% unknown.
There was a significant difference in etiology by site
of presentation (P <0.002). The distribution of eti-
ologies was not statistically different when those with
prior palpitations were compared to those without
prior palpitations
(P = 0.24).
Twenty-four patients were assigned more than one
etiology: 21 were coexisting psychiatxic illnesses (eg,
generalized anxiety disorder and panic disordler), 2 had
both symptomatic premature atrial and ventricular
beats, and 1 had coexisting cocaine and ctieine use.
Of the 159 patients for whom an etiology could be
determined, 148 were definite, 10 were probable, and
1 was possible. In the miscellaneous category, there
were 4 probable medication and habit etiologies and
1 possible medication/thyrotoxicosis etiology. In the
psychiatric category, there were 3 probable anxiety
etiologies. In the cardiac category, there were 3 prob-
able arrhythmias. (See Methods section for specific
definitions).
Table
IV lists selected variables (ie, demographic,
historical, and symptom characteristic) and their re-
lationship with the four categories of etiology. The
cardiac group had the highest mean age and the great-
est percentage of males, and its patients were more
likely to describe an irregular heart beat and report
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TABLE V
Multivariate Predictors of Cardiac Etiology
Odds 95% Confidence
Ratio Interval
Male sex 2.6 1.2 to 5.4
Description of an irregular beat
3.2
1.5 to 6.8
History of heart disease 3.5 1.6
to 7.8
>5minute duration of
5.7
2.4 to 13.7
palpitation event
TABLE VI
Evaluation Methods and the Number of Patients for
Whom Each Test Revealed the Etiology of Palpitations
Initial database
History and physical alone
13
Electrocardiogram’+ 43
Laboratory alone
5
History and physical plus laboratory
3
Diagnosis suggested by history and physical
4
Diagnostic Interview Schedule 55
Monitoring’
Telemetry
12
Halter monitor
8
Loop monitor
3
Telemetry plus Holter
2
Dthert
Electrophysiologic study
3
Echoaardiogram
1
Aortogram
1
Pacemaker evaluation
1
Previous diagnosis or evaluation
5
Total
159s
‘The numberof tests performed or arrhythmiadetection was as follows: 166
electrocardiograms, 79 radioelectrocardiograms telemetty), 53 Hotter mom
itors, 10 oop monrtors,10electrophysiologtcstudies,and 2 pacemakereval-
uations.
‘Pacemaker evaluation plus electrocardiogram was diagnostic in
1
patient.
$The number of selected other tests performed was as foltows: 93 chest
roentgenograms, 48 echocardiograms, 16 exercise treadmill tests, 9 car-
diac catheterizations, and 6 muitigated angiograms.
§Anetiology could not be determined n 31 patients.
the duration of their palpitation event as greater than
5 minutes. The highest mean number of associated
symptoms was reported by patients in the psychiatric
group. One variable that did not distinguish the eti-
ologies was a history of prior palpitations.
After the noncardiac etiologies were combined and
compared to the cardiac etiology group, we found six
clinically meaningful variables that were significant
univariate predictors of a cardiac etiology of palpita-
tions (P ~0.05). These variables were olde r age (con-
tinuous), male sex, description of an irregular heart
beat, history of heart disease, duration of palpitation
event >5 minutes, and fewer number of associated
symptoms (continuous variable). When these vari-
ables were entered into a multivariate logistic regres-
sion model, male sex, description of an irregular heart
beat, history of heart disease, and event duration of
>5 minutes were found to be independent predictors
of a cardiac etiology (Table V). Although~ univa,ria~~
analysis revealed that presentation to the emergency de-
partment compared with the medical clinic ‘was associ-
ated with a cardiac etiology of palpitations (P <0.002),
this was not a significant multivariate predictor of car-
diac etiology (odds ratio 2 .03, 95% confidence interval
0.76 to 5.4). None of the 17 patients with 0 predictors
had a cardiac etiology, 13 (26%) of the 50 pa,tients with
1 predictor had
a cardiac
etiology, 28 (48%)) of t.he 58
patients with 2 predictors had a cardiac etiology, 22
(71%) of the 31. patients with 3 predictors had a car-
diac etiology, and 9 (90%) of the 10 patients with all 4
predictors had a cardiac etiology . Twenty fcmr patients
with missing data were excluded from this analysis.
The area under the ROC curve for this model was 0.79
(standard deviation of the area = 0.04).
Diagnostic Testing
Table VI describes the evaluation of Ipatients in
terms of the types of tests ordered, as well as the num-
ber of patients for whom a diagnostic test led to the
etiology of palpitations. The basic patient evaluation
consisted of a history and physical (completed in
loo%?),psychiatric screening with the GHQ (completed
in 76%), and arrhythmia detection (ECG completed in
87%, prolonged electrocardiographic monit80ring com-
pleted in 64%). The performance of history and physi-
cal examination, ECG, and prolonged electrocardio
graphic monitoring was not significantly different
(P >0.2) between patients who had a known etiology
of palpitations and those who had unknown etiology.
Of the 159 patients for whom a diagnosis could be
made, 64 (40%) were accomplished with either the his-
tory and physical
examination, an ECG, and/or labo-
ratory data The laboratory data that was diagnostic in
8 patients included thyroid function studies and serum
theophylline level and hematocrit determinations.
Cardiac arrhythmia etiologies were detected by
ECG in 43 patients and by prolonged electrocardio-
graphic monitors in 25 patients; of the remlaining 122
patients, 110 (90%) underwent electrocardiography or
prolonged electrocardiographic monitoring, how-
ever, none of these tests revealed the etiology of pal-
pitations. There was no evidence for gender, age, or
racial bias in the performance of ECG or monitoring.
There was no evidence for bias in the performance
of monitoring based on site of presentation. An ECG
was more likely to be performed if the patient pre-
sented to the emergency department (94:0/o), ather
than any other site (78%); conversely, an ECG was
less likely to have been performed if the patient pre-
sented to the medica l clinic (70?), ra ther than any
other site (95%) (P ~0.01).
Psychiatric screening instruments were completed
by 144 (76%) patients. A GHQ score 25 and/or SOM
score 23 was found in 73 individuals. The DIS was ad-
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PATIENTS WITH PALPITATiONS/VVEBER AND KAPOOR
ministered to these 73 patients and to an additional
23 patients with clinical features suggestive of a pos-
sible psychiatric illness. Of the 96 patients assessed
by the DIS, one or more psychiatric illness was diag-
nosed in 78 patients (for a total of 154 diagnoses).
Additionally, 4 other patients were felt to have clini-
cally significant psychiatric illness (3 with anxiety, 1
with depression and suicidal ideation). The diagnoses
made by DIS were panic attack and/or disorder (n =
69), generalized anxiety disorder (n = 39), somatiza-
tion disorder (n = l), and depression (n = 45). The
majority of patients (52 of 78) had 2 or more coex-
isting psychiatric illnesses; most frequently, depres-
sion accompanied one of the other disorders (n = 41).
There were significantly more DIS performed in non-
white (65%) than white (45%) patients (P ~0.02).
Ultimately, 58 of these 82 patients (55 with a positive
DIS, 3 with a clinical diagnosis) were assigned to the
psychiatric etiology group (Table Ill); 5% (29/55) of
these patients were also depressed, however depres-
sion was considered to be comorbid and not etiologic.
There were 19 patients with a positive DIS in whom
the psychiatric illness was considered to be comor-
bid and not etiologic. The assigned etiologies in these
patients were: arrhythmias in 14, medications in 2,
thyrotoxicosis in 1, and unknown in 2. These 2 pa-
tients were categorized as unknown etiology instead
of psychiatric etiology because one had coexisting al-
coholism and the second had a remote history of the
psychiatric disorder.
Follow-Up
By October 28, 1992, follow-up was completed in
98%of the patients. At least l-year follow-up (365 days
+ 14 days) was available for 96%of the patients.
Table
VII details the outcomes at final follow-up. All reports
of stroke were confirmed by the medical record.
Mortality was documented in 3 patients; none of the
deaths was sudden. One death was due to a sub-
arachnoid hemorrhage in a patient taking warfarin fol-
lowing aortic valve replacement for aortic insuffi-
ciency. The second death was due to congestive heart
failure and renal failure in a patient following a stroke.
The third death was due to severe congestive heart fail-
ure in a patient with cell&is and soft-tissue abscess.
There were 2 patients with new arrhythmias docu-
mented in follow-up; it is probable that these were re-
sponsible for the original palpitations. One patient,
originally in the unknown category, had symptomatic
correlation of palpitations with premature ventricular
beats upon repeat presentation. Another patient with
increasing symptoms, originally in the psychiatric cat-
egory, had documentation of symptomatic correlation
of palpitations with supraventicular tachycardia.
The percent with recurrent palpitations varied by
etiology; however, this difference was only significant
TABLE VII
Outcomes at Final Follow-Up
Mortalitv 1%)
Stroke 1%)
. .
-
Cardiac (n = 82)
1 (1.2)
1 (1.2)
Psychiatric (n = 58)
l(1.7)
0
Miscellaneous (n = 19)
1 (5.3)
1 (5.3)
Unknown (n = 31)
0
0
Total’ (n =
190)
3 (1.6)
2 (1.1)
‘One-year mortakty and stroke rates were determined by the Kaplan-Meier
method. The 95% confidence interval for the total mortality rate was 0%
to 3.4% and for the total stroke rate was 0% to 2.6%. Mean and median
follow-up times for both stroke and death exceeded 365 days.
at the first follow-up when recurrent symptoms were
experienced by 61% of the psychiatric group, 53% of
the cardiac group, 17% of the miscellaneous group,
and 48% of the group with an unknown etiology
(P ~0.02). By the last follow-up, 75%of all patients re-
ported recurrent symptoms. This rate of recurrent
symptoms varied by history of prior palpitations; 79%
of the patients with and 61% of the patients without
a prior history of palpitations had recurrent events
within the follow-up period (P ~0.03).
At 1 year, 95% of the patients were satisfied with
the care they received for their palpitations. Eighty-
nine percent reported that their health was the same
or improved compared to 1 year before. Of those
working outside of the home (52%of the cohort), work
performance was impaired in 19%, nd workdays were
missed by 1%. Because of palpitations, 33% eported
accomplishing less than usual work at home.
DISCUSSION
Although palpitations are a common symptom,
there are very limited descriptive, etiologic, or prog-
nostic data for nonreferred patients on this subject.
This is the first study that describes the etiologies of
palpitations and the outcomes of patients in a cohort
of patients presenting for care at a university-based
medical center.
We found that (1) an etiology could be dletermined
in 84%of the cohort, (2) 40%of those etiologies could
be determined with the history and physical exami-
nation, an ECG, and/or laboratory data, 113) sychi-
atric illnesses were common causes of palpitations,
and (4) the prognosis was excellent except that most
patients continued to have recurrent symptoms.
Our finding that only 16%of patients had no clear
etiology for their palpitations differs from research
on other common symptoms in primary care. In a 3-
year incidence study analyzing the probable etiology
of 14 common symptoms in 1,000 internal medicine
outpatients, Kroenke and Mangelsdorf? 7 reported
that the percent of each symptom with an unknown
etiology ranged from 47% for insomnia to 100% or
constipation.
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A wide variety of etiologies were diagnosed in this
population of patients with palpitations. Previous re-
ports of the etiology of palpitations are limited to stud-
ies of patients referred for ambulatory electrocardio-
graphic monitoring. 2a42 These studies report the
arrhythmias recorded by ambulatory electrocardio-
graphic monitoring, however not all studies indicate
the relationship between symptoms reported and ar-
rhythmias detected. The reported yield of ambulatory
electrocardiographic monitoring in the detection of
symptomatic arrhythmias ranges from 13% o 69%..“541,@
However, referral bias and the inclusion of patients
with symptoms other than palpitations in most of
these studies raise concerns about the generalizabil-
ity of these findings. The prevalence of the various eti-
ologies of palpitations may also be misrepresented by
case series of patients with specific diseases associ-
ated with the symptom of palpitations.44
Psychiatric illness was frequently diagnosed and
was associated with the highest rate of recurrent
symptoms at 3 months. Palpitations are one of the
DSM-III-R d iagnostic criteria for panic attack , gener-
alized anxiety disorder, and somatization disorder.20
Although depression may be a comorbid illness, we
did not consider this to be an etiology of palpitations.
Previously published data from our own general med-
ical clini~,~~@ documented a 9.2% prevalence of major
depressive disorder and 1.7% prevalence of panic dis-
order in primary care populations. Depressed patients
had more physical illness, somatic symptoms, and dis-
ability than nondepressed patients. It is likely that de-
pression may result in palpitations, but 41 of 45 of our
patients with depression had other coexisting psychi-
atric illness. Thus, we were unable to clarify the role
of depression in leading to palpitations. As suggested
by Bar~ky ,~ further studies of the relationship between
common symptoms such as palpitations and psychi-
atric illness are needed, since there is evidence for sig-
nificant unrecognized psychiatric morbidity in ambu-
latory care patients with common medical symptoms.
Based on our findings, assessment for generalized
anxiety, panic, and somatization disorders and de-
pression should become an important focus of evalu-
ation of patients with palpitations.
We identified four variables that were independent
predictors of a cardiac etiology of palpitations. This
model performed better than chance, as demonstrated
by the area under the ROC curve. However, the pre-
diction of a cardiac etiology must be interpreted with
caution because (1) assignment to the cardiac etiol-
ogy group does not necessarily imply a higher mor-
tality, (2) further testing beyond the initial database
may not be required to make this diagnosis, and (3)
diverse etiologies were included in the cardiac group.
Palpitations were associated with low mortality
and cardiac morbidity. Despite the high prevalence of
cardiac disease, mortality was documented in only 3
women over the age of 70. None of the (deaths was
sudden or directly related to the original etiology of
palpitations. In the only other study of outcomes in
patients with palpitations5 the proportion experienc-
ing a cardiac endpoint (ie, myocard ial infarction, ven-
tricular tachycardia, ventricular fibrillation, cardiac
arrest, or death) in 5 years was similar between cases
with palpitations (6.4%) and clinic-based controls
(7.2%). In only 4 patients was ventricular t,achycardia
responsible for the symptom of palpitations. The l-
year mortality rate of 1.6% in patients with palpita-
tions is in striking contrast to our experience with
syncope, where there is a 28% mortality ;md 15% in-
cidence of sudden death at 1 year in patients with car-
diac etiologies.47
In contrast, the morbidity from palpitations was
substantial. Although 77% had prior palpitations, it
was surprising that the majority of patients with and
without a history of prior palpitations had recurrent
symptoms. This is in contrast to the 35% of syncope
patients with recurrent symptoms at 5 years.“7 The re-
currences appeared to have substantial effect
on
qual-
ity of life since at least one third of the patients re-
ported accomplishing less than usual work in the
home and a smaller fraction had impaired work per-
formance or missed work. These data suggest that
this common symptom has characteristics similar to
a chronic disease with exacerbation and remission of
symptoms over time.
Limitations of this study should be acknowledged.
First, we did not assemble an inception co‘hort by lim-
iting our patient enrollment to those with new onset
of palpitations because patients often could not define
the first onset of this symptom. Despite this limitation,
our findings are relevant to the patients seen with pal-
pitations since the vast majority of patients present
with chronic symptomatology. Second, not all patients
underwent all diagnostic tests. Specifically, the DIS
was performed less frequently in patients for whom an
etiology could not be determined. We believe this is
not a major limitation since, surprisingly, an etiology
could be determined in the majority of the patients.
Based on this study, we suggest the following strat-
egy for a practical evaluation of patients with pa lpi-
tations. A careful history, physical examination, and
ECG along with selective use of laboratory tests will
identify the etiology of palpitations in close to half of
the patients. In the remaining patients, a major focus
should be screening (with the GHQ) for psychiatric
disorders to detect generalized anxiety, panic, and de-
pression. In those without a diagnosis who have heart
disease, palpitations lasting longer than 5 minutes, or
irregular beats, prolonged cardiac monitoring may
show an etiology of palpitations. Since symptomatic
correlation is critical in determining whether an ar-
PATIENTS WITH PALPITATIONS/WEBER AND KAPOOR
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rhythmia is the etiology o f palpitations, event moni-
toring appears to be well suited for diagnostic evalu-
ation of this symptom.31 Electrophysiologic testing
should be reserved for specific high-risk groups such
as patients with accessory pathways or when therapy
of documented arrhythmias is needed.@
In conclusion, the etiology of palpitations can of-
ten be diagnosed with a simple initial evaluation.
Psychiatric illness accounts for the etiology in nearly
one third of all patients with palpitations. The short-
term prognosis of patients with palpitations is excel-
lent; however, the recurrence rate is high. Future
studies are needed to develop interventions that may
decrease recurrent symptoms in these patients and
improve their quality of life.
ACKNOWLEDGMENT
We are Indebted o Nancy Brant Miller, CRNP, or the administration of the DIS,
Karen Brich, PA-C, or comple ting patient follow-up, Barbara Hanusa, PhD, or
statistical assrstance , Terry Sefcik, MSc, for data managementguidance, Lisa
Joseph or data entry, and Roberta Eckman or manuscript preparation
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12. Finlay-JonesRA, Murphy E. Severity of psychiatric disorder and the 30ii tem
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evolution, and use. Sot PsychratrEpidemiol. 1988;23:6-16.
18. Robins LN, Helzer JE, Croughan J, Ratcllff KS. National lnstttute of Mental
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19. Paulsen AS, Crowe RR, Noyes R, Pfohl B. Rehabrlity of the telephone
intervrew in diagnosing anxiety disorders. Arch ‘C;en Psychiatry.
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APPENDIX
Diagnostic Criteria Used for the
Categorization of the Etiologies of Palpitations
Arrhythmias. Any new deviation from normal si-
nus rhythm or a significant change in the rate of a sta-
ble arrhythmia (eg, atrial fibrillation) can cause the
symptom of palpitations.
Definite: Symptomatic correlation of palpitations
with the arrhythmia recorded on electrocardiographic
monitoring.
&oba&: Greater than 5 beats of supraventricular
tachycardia or ventricular tachycardia in the absence
of symptomatic correlation.
Increased Stroke Volume. Stroke volume may be
increased with cardiac and extracardiac shunts13 or
regurgitant valvular heart disease.4 Palpitations may
be noted at different stages, so general gu idelines were
used to determine causality.
0 Cardiac and extra-cardiac shunts. A cardiac shunt
was considered causal if there was either echocar-
diographic or cardiac catheterization documentation
of moderate to severe shunt flow in a patient with
palpitations. Any extra-cardiac arteriovenous fistula
in a patient with pa lpitations was considered causal
if no other etiology was present.
0 Regurgitant valvular heart disease. Valvular heart
disease such as mitral regurgitation and aortic insuf-
ficiency was considered causal if there was either
echocard iographic or cardiac catheterization docu-
mentation of moderate or severe regurgitant flow in
a patient with constant palpitations and no concur-
rent arrhythmia.
Pacemaker. Paced beats or intercostal muscle and
diaphragmatic flutter may be sensed by the patient
with a pacemaker. Pacemaker syndrome may also be
associa ted with palpitations5 To be considered
causal, the sensed beats must have been correlated
with the paced beats.
Prosthetic Heart Valve. Each heart beat in a pa-
tient with a prosthetic heart valve may be sensed and
reported as constant palpitations.4 To be considered
causal, the sensed beats must have been correlated
with the normal heart rhythm.
Cardiac Disease. Various cardiac diseases have
been associated with palpitations in the absence of
arrhythmias or other causes for palpitations. These
reports were interpreted to define causality.
0 Cardiomegaly. The enlarged cardiac silhouette
can cause palpitations, probably on the basis of in-
creased cardiac output or contractility. This was con-
sidered causal if there was chest radiographic evi-
dence of at least moderate cardiomegaly in a patient
with palpitations.
l
Mitral Valve Prolapse (MVP). Although the liter-
ature reports series of patients with MVP in whom
there is symptomatic correlation of arrhythmias on
ambulatory monitoring, there are also patients with
symptoms in the absence of arrhythmias.fi-8 For the
patient with clinical (ie, classic murmur or click) or
echocardiographic evidence of mitral valve prolapse
and palpitations, MVP was considered causal in the
absence of symptomatic arrhythmias. Patients in
whom symptomatic arrhythmias were documented
were classified as an arrhythmia etiology.
l Hyperkinetic heart syndrome. Classification into
this category was limited to young males -with a sys-
tolic murmur and a hyperdynamic precordium and
pulse, in the absence of any other etiology for a hy-
peradrenergic state.gJO
l Atrial myxoma Although this entity is rare, there
have been reports of atrial myxoma presenting with
palpitations.
l1 For the patient with echocardiographic
evidence of atrial myxoma and palpitations, the myx-
oma was considered causal in the absence of symp-
tomatic arrhythmias.
Psychiatric Disease . Palpitations commonly oc-
cur in patients with panic attack and disorder, gen-
eralized anxiety disorder, and somatization disorder
and are included in their Diagnostic and Statistical
Manual of Mental Disorders, Third edition, Revised
(DSM-IILR) deftitions.12
Definite: A diagnosis of one or more of’ these dis-
orders was made if the patient met DSM-III-R crite-
ria as diagnosed with Diagnostic Interview Schedule
@IS).‘3J4
and there was no other signiticant medica l
comorb idity or etiology for palpitations.
Probable: When the DIS was not administered but
there was strong clinical evidence, the investigators
considered a category of probable anxiety to fit the
DSM-III-R category of generalized anxiety d isorder
that was not otherwise specified.
Cmorbid: In cases in which any other etiology for
palpitations existed, the psychiatric disorder was not
considered as the etiology.
Medications. Palpitations occurring with a tem-
poral relationship to the use of medications such as
sympathomimetic agents, vasodilatom, anticholiner-
gics, or during withdrawal from S-blockers are well
recognized.15 Each potential etiologic medication
must have been reported to cause palpitations as a
possible adverse effect. Criteria were devised to jus-
tify causality, similar to previous reports on adverse
drug reactions. l6
Definite: (1) Palpitations following a temporal se-
quence after the medication was introduced or
reached an abnormal level, (2) resolving after with-
drawal o f the medication or normalization of the
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blood concentration, and (3)
having
no other appar-
ent etiologic factor.
Probable: Two of the three factors listed above.
Possible: One of the three factors listed above OR
two of the three factors listed above in the presence
of another etiologic factor.
Habits. Palpitations occurring with a temporal re-
lationship to the use of cocaine17-1g and ampheta-
mines,15 caffeine,2@23 and nicotine15 have been re-
ported. Criteria have been developed to define this
association.
0 Cocaine or amphetamines
Definite: (1) Palpitations temporally related to co-
caine or amphetamine use, (2) with resolution after
discontinuation of the drug, and (3) no other appar-
ent etiology.
Probable: Palpitations tempora lly related to co-
caine or amphetamine use and one of the other two
factors listed above.
Possible: Palpitations temporally related to co-
caine or amphetamine use, but other possible eti-
ologies exist.
0 Caffeine
Definite: (1) Palpitations temporally related to caf-
feine intake of greater than 4 cups of coffee (or equiv-
alent) per day, (2) with resolution after discontinua-
tion of caffeine, and (3) no other apparent etiology.
Probable: Palpitations tempora lly related to caffeine
intake of greater than 2 cups of coffee (or equivalent)
per day and one of the other two factors listed above.
Possible: Palpitations tempora lly related to any caf-
feine intake, but other possible etiologies exist.
0 Nicotine
Definite: (1) Palpitations temporally related to
nicotine product use, (2) with resolution after cessa-
tion, and (3) no other apparent etiology.
Probable: Palpitations tempora lly related to nico-
tine product use and one of the other two factors
listed above.
Possible: Palpitations temporalIy related to nico-
tine product use, but other possible etiologies exist.
Metabolic Disorders. Several metabolic disor-
ders have been reported to be associated with palpi-
tations and are often accompanied by a sinus tachy-
cardia. These abnormal metabolic states are often
recognized by other characteristic associated signs
and symptoms.
0 Hypoglycemia.
24Hypoglycemia was documented
in association with palpitations that resolved with
restoration of normal glucose levels.
0 Thyrotoxicosisz5 Palpitations were associa ted
with the clinical presence of thyrotoxicosis, con-
firmed by laboratory tests.
0 Pheochromocytoma.
26 Palpitations were associ-
ated with the clinical presence of pheochromocy-
toma, confiied by laboratory tests.
l Mastocytosis. 27Palpitations were associa ted with
the clinical presence of mastocy tosis, confirmed by
laboratory tests.
l
Scombroid food poison&g.2x Palpitations follow-
ing ingestion of scombroid fish.
0 Idiopathic
flushing.
2g The clinical scenario was
consistent with idiopaQic flushing and other disor-
ders were excluded (ie, diagnosis by exclusion).
High Output States. Increased cardiac output can
be responsible for the symptom of palpitations. The
conditions listed below are known causes of a high
output state . The following definitions were used to
relate the palpitations to the high output state:
0 Anemia1n30 There is no clear level of hemoglobin
at which the cardiac output rises. Symptoms vary
with the rate of onset of anemia and the underlying
comorb idity of the patient. For the purpose of this
study, anemia was considered causal if palpitations
occurred in a patient with a hemoglobin < 100 g/L and
resolved after correction of the anemia.
0 Pregnancy.31 Peak cardiac output occurs between
the 20th and 24th week of gestation. Palpitations in a
pregnant woman after the 20th we(3k of gestation
were attributed to the high output state of pregnancy
when no other etiology was present.
0 Paget’s disease.1B32Cardiac output rises .when
more than 15% of the skeleton is involved with active
Paget’s disease. For the purpose of this study, Paget’s
disease was considered causal in a patient with pal-
pitations if there was active disease of at least two
skeletal locations and no other etiology was present.
0 Fever.33 There is a linear relationship between
rise in temperature above normal and the heart rate.
As baseline heart rate varies among individuals, so
will the appearance of tachycardia Fever was con-
sidered causal when palpitations were tempora lly re-
lated to a new temperature of 238” C, with resolution
after defervescence, if no other etiology was present.
Dehydration and Orthostatic Hypotension.
Palpitations occurring in the patient with dehydration
or orthostatic hypotension are generally be lieved to
be related to a physiologic (compensatory) sinus
tachycardia. These were considered present in the ap-
propriate clinical setting if clinical or laboratory signs
of dehydration or symptomatic orthostatic hypoten-
sion existed.%
Exertion. Exertional palpitations are related to an
increased stroke volume. Exertion was considered
causal if historical data confirmed physical exertion
for that $iividual, in the absence of another etiology
of palpitations.
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