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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 palpitations, (2) the usefulness of diagnostic tests in
determining the etiologies of palpitations, and (3)
the outcomes of patients with palpitations.
PAIIENTS AND METHODS:
One 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 psychiatric 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 followup was obtained in 96% of the patients.
RESULTS An etiology of palpitations was determined in 84% of the patients. The etiology of palpitations 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 electrocardiogram, 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 palpitations. 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 accomplishing less than usual work at home.
CONCLUSIONS: The etiology of palpitations can often 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 for 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.
138
February
1996 The American Journal of Medicine”
there is a high rate of recurrence of symptoms
and a moderate impact on productivity.
P
alpitations are one of the most common symptoms 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 lifethreatening conditions such as ventricular tachycardia2 to various psychiatric illnesses.3 As a result, patients with palpitations often undergo a wide variety
of diagnostic tests and referrals leading to substantial resource utilization.* Currently, clinical experience guides the physician caring for patients with palpitations, 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 palpitations has not been well described. In the only retrospective study of outcomes in patients with palpitationq5 cases with palpitations and controls without
palpitations experienced similar rates of cardiac endpoints. The purpose of this prospective study was to
determine (1) the etiologies of palpitations, (2) the
usefulness of diagnostic tests in determining the etiologies of palpitations, and (3) the outcomes of patients with palpitations.
PATIENTS AND METHODS
This was a prospective cohort study of patients presenting with palpitations. Palpitations were defined
as one or more of the following patient complaints:
fast heart beats, skipped heart beats, irregular heart
rate, and heart fluttering, racing, or pounding.”
Study Entry Criteria
Between January 2 and August 30, 1!391, all patients presenting to the emergency department, admitted to the medical and surgical inpatient service,
or attending the medical 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 eligibility. 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,
Volume 100
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 diagnosis for admission or discharge, and patients with
palpitations are often labeled with a more specific diagnosis, a comprehensive search strategy was used
to capture all patients with palpitations. To identify
patients eligible for the study, we performed daily review of the following lists: emergency department discharge diagnoses, hospital admission diagnoses, and
outpatient visit discharge diagnoses. If any of the diagnoses 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 palpitations. In cases in which this could not be ascertained, the patient was contacted for clarification.
Patients who met the entry criteria were asked to participate in the study. Conduct of the study was approved by the institutional review board of the
University of Pittsburgh.
TABLE I
Diagnoses Used to Identify Patients
Anemia
Transfusion
Anxiety
Aortic aneurysm
Arrhythmia
Specific arrhythmias (ie, atrial fibrillation, atrial flutter, bradycardia, 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
Patient Evaluation
Patients who agreed to participate were interviewed. The structured interview was directed at the
following issues: palpitation characteristics,
associated symptoms and situations, drug and medication
use, and comorbid illness. Medical charts were reviewed and data were abstracted regarding physical
examination findings and results of the diagnostic
evaluation. This process was completed by the principal 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, evaluation and interview was 2, and event and interview was
2. The physical exam and diagnostic evaluation (ie,
electrocardiogram [ECG], laboratory tests, arrhyLhmia detection) was determined by the individual
physician seeing the patient at the index visit. In cases
in which tests for arrhythmia detection were not ordered by the clinician, the investigators made loop
monitors available.
To screen for generalized anxiety disorder, panic attack, panic disorder, major depression, and somatization disorder, patients were asked to complete two validated self-administered instruments: the General
Health Questionnaire (GHQ),7-12and the somatization
screening test of Othmer and DeSouza13(SOM). The
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 score14J5of 25 or a SOM
score16of 23 or in whom these psychiatric illnesses
were clinically suspected were further assessedwith
the Diagnostic Interview Schedule (DIS)17Jssections
for generalized anxiety disorder, panic attack and disorder, 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>2Ocriteria 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 lifetime 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-
February 1996 The American Journal of Medicinea Volume 100
139
TABLE Ill
TABLE II
Patient Characteristics
Mean age (yl
Range
Female
White
21 year of college education
Site of presentation
Emergency department
Medical clinic
Symptom presentation
Chief complaint
Complaint during a routine visit
Admitted to hospital
History of prior palpitations
History of
Heart disease+
Hypertension
Congestive heart failure
Diabetes mellitus
(N = 190)’
46
18-87
61
74
57
62
28
87
13
35
77
32
29
13
7
‘Other than mean age, data shown represent the percentage of patients
included.
‘Coronary (ie, history of myocardial infarction, angina, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty), congenital, 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 categorization of the etiologies of palpitations. Cardiac etiology included arrhythmias, cardiac and extra-cardiac shunts, regurgitant vahular heart disease,
pacemaker, prosthetic heart valve, cardiomegaly, mitral valve prolapse, hyperkinetic heart syndrome, and
atrial myxoma. Psychiatric etiology included panic attack, panic disorder, generalized anxiety disorder,
and somatization disorder. The category of miscellaneous etiology included medications, habits, metabolic disorders, high output states, dehydration and
orthostatic hypotension, and exertion.
Given the available information (ie, history, physical, diagnostic evaluation, psychiatric testing), the investigators 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 arrhythmia was assigned. The remaining etiologies
were carefully considered for their presence or absence. This hierarchy always designated cardiac arrhythmias as the etiology, although psychiatric or
metabolic comorbid conditions may have been present. 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
140
February
1996 The American Journal of Medicine*
Etiologies of Palpitations
No.
Cardiac
82
Atrial fibrillation
19
Supraventricular tachycardia
18
Premature ventricular beats
15
Atrial flutter
11
Premature atrial beats
6
Ventricular tachycardia
4
Mitral valve prolapse
2
Sick sinus syndrome
2
Pacemaker failure
2
Aortic insufficiency
2
Atrial myxoma
1
Psychiatric
58
Panic attack or disorder plus anxiety
20
Panic attack alone
17
Panic disorder alone
14
Anxiety alone
6
Panic plus anxiety plus somatization
1
Miscellaneous
19
Medication
5
Thyrotoxicosis
5
Caffeine
3
2
Cocaine
2
Anemia
Amphetamine
1
1
Mastocytosis
Unknown
31
Percent
43.2
10.0
9.5
7.9
5.8
3.2
2.1
1.1
1.1
1.1
1.1
0.5
30.5
10.5
8.9
7.4
3.2
0.5
10.0
2.6
2.6
1.6
1.1
1.1
0.5
0.5
16.3
habits were considered to be definite, probatble,or possible, adapted from the literature on adverse drug effects.*l Arrhythmias (only supraventricular tihycardia and ventricular tachycardia) and anxiety were
considered definite or probable. Only 5.8%of the patients had etiologies that were considered probable or
possible. As this is the first study to explore the etiologies for the symptom of palpitations, our focus was
on the spectrum of etiologies; therefore, for the analyses presented here, the categories of definite, probable, and possible were combined. These diamostic criteria allowed patients to be assigned to only one
etiology category, but could have more than one diagnosis 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 recurrences, new cardiovascular events, and mortality
were obtained from the patient, the family, or caregiver; interviewers were trained to avoid leading questions and to be specific with respect to morbidity related only to palpitations. All interviews were
completed by October 28, 1992; over 90% of inter-
Volume 100
PATIENTS WITH PALPITATlONS/WEBER AND KAPOOR
TABLE N
Selected Significant Variables and Their Relationship to Etiology’
Cardiac
Psychiatric
Miscellaneous
Demographic
Mean age (y)
Male sex (%I
White (%)
Comorbidity
History of heart disease (%I
Symptom characteristics
Irregular heart beat (%)
Duration >5 minutes (%I
Total number of symptoms @I!-131
Unknown
50
51
85
41
29
67
46
26
74
47
32
58
45
19
16
32
34
21
67
4.3
50
50
2.9
::
51
3.5
5.3
'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- gender from those who refused. Selected features of
tant. Whenever follow-up events occurred, attempts the 190 enrolled patients are shown in Ttible Il.
were made to obtain further details from the primary
physician and medical chart. The cause of death was Etiologies
assigned on the basis of information obtained from
An etiology for palpitations was assigned in 159
the patient’s family and the medical chart.
[84%) patients. The specific etiologies are listed in
Table III. Overall, 43%of the patients had1a cardiac
Statistical Analyses
etiology, 31%had a psychiatric etiology, 10%had misStandardized forms for entry of clinical, laboratory, cellaneous etiologies, and 16%were unknown. For the
and outcome data were utilized. Data management and subgroup of patients presenting to the medical clinic,
analyses were conducted with the use of RBase the etiology was cardiac in Zl%, psychiatric in 45%,
(Microrim Inc, Seattle, Washington),22 BMDP (UC miscellaneous in 696,and 28% unhewn. For the subPress, Berkeley, California),23 StatXact (Cytel Corp, group of patients presenting to the emergency deCambridge, Massachusetts),24and ROCFIT (University partment, the etiology was cardiac in 47%,psychiatric
of Chicago, Chicago, Illin~is)~~ software packages. in 27%, miscellaneous in 13%, and 13% unknown.
Statistical tests included the &i-square, Fisher’s exact, There was a significant difference in etiology by site
and analysis of variance tests to evaluate differences of presentation (P <0.002). The distribution of etibetween groups. Logistic regression analysis (BMDP ologies was not statistically different when those with
LRa) was used to test for independence among pre- prior palpitations were compared to those without
dictors of a cardiac etiology of palpitations. Our intent prior palpitations (P = 0.24).
was to create a clinical prediction model that incorTwenty-four patients were assigned more than one
porated variables readily available in the initial history. etiology: 21 were coexisting psychiatxic illnesses (eg,
All variables tested were dichotomous, including the generalized anxiety disorder and panic disordler), 2 had
composite variable ‘history of heart disease’, which both symptomatic premature atrial and ventricular
was considered present if any of the following was pre- beats, and 1 had coexisting cocaine and ctieine use.
Of the 159 patients for whom an etiology could be
sent: histow of angina, myocardial infarction, cardiac
surgery, percutaneous lxansluminal coronary angio- determined, 148were definite, 10 were probable, and
plasty, pulmonary hypertension, congestive heart fail- 1 was possible. In the miscellaneous category, there
ure, and va,lvular or congenital disease.To evaluate this were 4 probable medication and habit etiologies and
1 possible medication/thyrotoxicosis etiology. In the
prediction model, a receiver-operatingxharacteristic
(ROC) curve25was constructed based on the number psychiatric category, there were 3 probable anxiety
of multivariate predictors of cardiac etiology present. etiologies. In the cardiac category, there were 3 probOne-year mortality and stroke rates were calculated able arrhythmias. (See Methods section for specific
definitions).
using the Kaplan-Meier method.26
Table IV lists selected variables (ie, demographic,
RESULTS
historical, and symptom characteristic) and their reEntry criteria were met by 229 patients. Thirty-nine lationship with the four categories of etiology. The
patients were not enrolled due to patient or physician cardiac group had the highest mean age and the greatrefusal. Therefore, 83% agreed to participate. Those est percentage of males, and its patients were more
agreeing to participate did not differ in age, race, or likely to describe an irregular heart beat and report
February 1996 The American Journal of Medicine’ Volume X00
141
TABLE V
Multivariate Predictors of Cardiac Etiology
Odds 95% Confidence
Ratio
Interval
Male sex
Description of an irregular
History of heart disease
>5minute duration of
palpitation event
beat
2.6
3.2
3.5
5.7
1.2 to 5.4
1.5 to 6.8
1.6 to 7.8
2.4 to 13.7
TABLE VI
Evaluation Methods and the Number of Patients for
Whom Each Test Revealed the Etiology of Palpitations
Initial database
History and physical alone
Electrocardiogram’+
Laboratory alone
History and physical plus laboratory
Diagnosis suggested by history and physical
Diagnostic Interview Schedule
Monitoring’
Telemetry
Halter monitor
Loop monitor
13
43
5
3
4
55
12
8
3
2
Telemetry plus Holter
Dthert
3
Electrophysiologic study
1
Echoaardiogram
1
Aortogram
1
Pacemaker evaluation
5
Previous diagnosis or evaluation
159s
Total
‘The numberof tests performed for arrhythmiadetectionwas as follows: 166
electrocardiograms, 79 radioelectrocardiograms(telemetty), 53 Hotter mom
itors, 10loop monrtors,10electrophysiologtcstudies,and 2 pacemakerevaluations.
‘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 cardiac catheterizations, and 6 muitigated angiograms.
§Anetiology could not be determined in 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 etiologies 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 palpitations (P ~0.05). These variables were older age (continuous), 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 variables were entered into a multivariate logistic regression 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
142
of a cardiac etiology (Table V). Although~ univa,ria~~
analysis revealed that presentation to the emergency department compared with the medical clinic ‘was associated with a cardiac etiology of palpitations (P <0.002),
this was not a significant multivariate predictor of cardiac 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 cardiac 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 number 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 completed in 64%). The performance of history and physical 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 history and physical examination, an ECG, and/or laboratory 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 electrocardiographic monitors in 25 patients; of the remlaining 122
patients, 110 (90%) underwent electrocardiography or
prolonged electrocardiographic
monitoring,
however, none of these tests revealed the etiology of palpitations. 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 presented to the emergency department (94:0/o),rather
than any other site (78%); conversely, an ECG was
less likely to have been performed if the patient presented to the medical clinic (70?), rather 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-
February 1996 The American Journal of Medicine” Volume 100
PATIENTS WITH PALPITATiONS/VVEBER
ministered to these 73 patients and to an additional
23 patients with clinical features suggestive of a possible psychiatric illness. Of the 96 patients assessed
by the DIS, one or more psychiatric illness was diagnosed in 78 patients (for a total of 154 diagnoses).
Additionally, 4 other patients were felt to have clinically 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), somatization disorder (n = l), and depression (n = 45). The
majority of patients (52 of 78) had 2 or more coexisting psychiatric illnesses; most frequently, depression accompanied one of the other disorders (n = 41).
There were significantly more DIS performed in nonwhite (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 depression was considered to be comorbid and not etiologic.
There were 19patients with a positive DIS in whom
the psychiatric illness was considered to be comorbid 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 patients were categorized as unknown etiology instead
of psychiatric etiology because one had coexisting alcoholism 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
+ 14days) 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 subarachnoid hemorrhage in a patient taking warfarin following aortic valve replacement for aortic insufficiency. 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 failure in a patient with cell&is and soft-tissue abscess.
There were 2 patients with new arrhythmias documented in follow-up; it is probable that these were responsible 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 category, had documentation of symptomatic correlation
of palpitations with supraventicular tachycardia.
The percent with recurrent palpitations varied by
etiology; however, this difference was only significant
AND KAPOOR
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 reported 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. Eightynine 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%,and workdays were
missed by 1%. Because of palpitations, 33%reported
accomplishing less than usual work at home.
DISCUSSION
Although palpitations are a common symptom,
there are very limited descriptive, etiologic, or prognostic 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 examination, an ECG, and/or laboratory data, 113)psychiatric 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 3year 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%for
constipation.
February
1996 The American Journal of Medicinea
Volume
100
143
PATIENTS WITH PALPITATIONS/WEBER
AND KAPOOR
A wide variety of etiologies were diagnosed in this
cardiac disease, mortality was documented in only 3
population of patients with palpitations. Previous re- women over the age of 70. None of the (deaths was
ports of the etiology of palpitations are limited to stud- sudden or directly related to the original etiology of
ies of patients referred for ambulatory electrocardiopalpitations. In the only other study of outcomes in
graphic monitoring. 2a42 These studies report the patients with palpitations5 the proportion experiencarrhythmias recorded by ambulatory electrocardioing a cardiac endpoint (ie, myocardial infarction, vengraphic monitoring, however not all studies indicate
tricular tachycardia, ventricular fibrillation, cardiac
the relationship between symptoms reported and ar- arrest, or death) in 5 years was similar between cases
rhythmias detected. The reported yield of ambulatory
with palpitations (6.4%) and clinic-based controls
electrocardiographic monitoring in the detection of (7.2%). In only 4 patients was ventricular t,achycardia
symptomatic arrhythmias ranges from 13%to 69%..“541,@ responsible for the symptom of palpitations. The lHowever, referral bias and the inclusion of patients
year mortality rate of 1.6% in patients with palpitawith symptoms other than palpitations in most of tions is in striking contrast to our experience with
these studies raise concerns about the generalizabilsyncope, where there is a 28% mortality ;md 15% inity of these findings. The prevalence of the various eti- cidence of sudden death at 1 year in patients with carologies of palpitations may also be misrepresented by diac etiologies.47
case series of patients with specific diseases associIn contrast, the morbidity from palpitations was
ated with the symptom of palpitations.44
substantial. Although 77% had prior palpitations, it
Psychiatric illness was frequently diagnosed and was surprising that the majority of patients with and
was associated with the highest rate of recurrent
without a history of prior palpitations had recurrent
symptoms at 3 months. Palpitations are one of the symptoms. This is in contrast to the 35% of syncope
DSM-III-R diagnostic criteria for panic attack, gener- patients with recurrent symptoms at 5 years.“7 The realized anxiety disorder, and somatization disorder.20 currences appeared to have substantial effect on qualAlthough depression may be a comorbid illness, we ity of life since at least one third of the patients redid not consider this to be an etiology of palpitations.
ported accomplishing less than usual work in the
Previously published data from our own general med- home and a smaller fraction had impaired work perical clini~,~~@ documented a 9.2% prevalence of major
formance or missed work. These data suggest that
depressive disorder and 1.7% prevalence of panic dis- this common symptom has characteristics similar to
order in primary care populations. Depressed patients
a chronic disease with exacerbation and remission of
had more physical illness, somatic symptoms, and dis- symptoms over time.
ability than nondepressed patients. It is likely that deLimitations of this study should be acknowledged.
pression may result in palpitations, but 41 of 45 of our First, we did not assemble an inception co‘hort by limpatients with depression had other coexisting psychiiting our patient enrollment to those with new onset
atric illness. Thus, we were unable to clarify the role
of palpitations because patients often could not define
of depression in leading to palpitations. As suggested the first onset of this symptom. Despite this limitation,
our findings are relevant to the patients seen with palby Bar~ky,~ further studies of the relationship between
pitations since the vast majority of patients present
common symptoms such as palpitations and psychiatric illness are needed, since there is evidence for sig- with chronic symptomatology. Second, not all patients
nificant unrecognized psychiatric morbidity in ambu- underwent all diagnostic tests. Specifically, the DIS
was performed less frequently in patients for whom an
latory care patients with common medical symptoms.
etiology could not be determined. We believe this is
Based on our findings, assessment for generalized
anxiety, panic, and somatization disorders and de- not a major limitation since, surprisingly, an etiology
pression should become an important focus of evalu- could be determined in the majority of the patients.
Based on this study, we suggest the following stratation of patients with palpitations.
egy for a practical evaluation of patients with palpiWe identified four variables that were independent
predictors of a cardiac etiology of palpitations. This tations. A careful history, physical examination, and
ECG along with selective use of laboratory tests will
model performed better than chance, as demonstrated
by the area under the ROC curve. However, the pre- identify the etiology of palpitations in close to half of
the patients. In the remaining patients, a major focus
diction of a cardiac etiology must be interpreted with
should be screening (with the GHQ) for psychiatric
caution because (1) assignment to the cardiac etiology group does not necessarily imply a higher mor- disorders to detect generalized anxiety, panic, and detality, (2) further testing beyond the initial database pression. In those without a diagnosis who have heart
may not be required to make this diagnosis, and (3) disease, palpitations lasting longer than 5 minutes, or
irregular beats, prolonged cardiac monitoring may
diverse etiologies were included in the cardiac group.
show an etiology of palpitations. Since symptomatic
Palpitations were associated with low mortality
and cardiac morbidity. Despite the high prevalence of correlation is critical in determining whether an ar144
February
1996 The American Journal of Medicine@ Volume 100
PATIENTS WITH PALPITATlONS/WEBER AND KAPOOR
rhythmia is the etiology of palpitations, event monitoring appears to be well suited for diagnostic evaluation 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 often be diagnosed with a simple initial evaluation.
Psychiatric illness accounts for the etiology in nearly
one third of all patients with palpitations. The shortterm prognosis of patients with palpitations is excellent; 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 Indebtedto Nancy Brant Miller, CRNP,for the administration of the DIS,
Karen Brich, PA-C,for completing patient follow-up, Barbara Hanusa, PhD, for
statistical assrstance, Terry Sefcik, MSc, for data managementguidance, Lisa
Joseph for data entry, and Roberta Eckmanfor manuscriptpreparation
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10. Vieweg BW, Hellund JL. The General Health Questionnatre (GHQ): A
comprehensive revrew. 1 OperationalPsychiatry. 1983;14:74-81.
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14. Newman SC, Bland RC, Om H. A comparison of the methods of scoring
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psychiatric screening tests. Br J Psychiatry. 1976;129:61-67.
16. Smith GR, Brown F. Screening indexes in DSM-IIIRsomatrzation disorder.
GenHasp Psychiatry. 1990;12:148-152.
17. Helzer JE, Robins LN. The dragnostic interview schedule: its development,
evolution, and use. Sot PsychratrEpidemiol. 1988;23:6-16.
18. Robins LN, Helzer JE, CroughanJ, Ratcllff KS. National lnstttute of Mental
Health Diagnostic Interview Schedule: its history, characterishcs, and validity.
Arch Gen Psychratry. 1981;38:381-389.
19. Paulsen AS, Crowe RR, Noyes R, Pfohl B. Rehabrlity of the telephone
intervrew in diagnosing anxiety disorders. Arch ‘C;en Psychiatry.
1988;45:62-63.
20. American Psychiatric Association, Committee on nomenclature and
statistics. Diagnosbc and Statistical Manual of Mental Disorders, 3rd ed,
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21. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the
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APPENDIX
Diagnostic Criteria Used for the
Categorization of the Etiologies of Palpitations
Arrhythmias.
Any new deviation from normal sinus rhythm or a significant change in the rate of a stable 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 guidelines were
used to determine causality.
0 Cardiac and extra-cardiac shunts. A cardiac shunt
was considered causal if there was either echocardiographic or cardiac catheterization documentation
of moderate to severe shunt flow in a patient with
palpitations. Any extra-cardiac arteriovenous fistula
in a patient with palpitations was considered causal
if no other etiology was present.
0 Regurgitant valvular heart disease. Valvular heart
disease such as mitral regurgitation and aortic insufficiency was considered causal if there was either
echocardiographic
or cardiac catheterization documentation of moderate or severe regurgitant flow in
a patient with constant palpitations and no concurrent arrhythmia.
Pacemaker. Paced beats or intercostal muscle and
diaphragmatic flutter may be sensed by the patient
with a pacemaker. Pacemaker syndrome may also be
associated 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 patient 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 increased cardiac output or contractility. This was considered causal if there was chest radiographic evi146
February
dence of at least moderate cardiomegaly in a patient
with palpitations.
l Mitral Valve Prolapse (MVP). Although the literature 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 systolic murmur and a hyperdynamic precordium and
pulse, in the absence of any other etiology for a hyperadrenergic 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 myxoma was considered causal in the absence of symptomatic arrhythmias.
Psychiatric
Disease. Palpitations commonly occur in patients with panic attack and disorder, generalized 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 disorders was made if the patient met DSM-III-R criteria as diagnosed with Diagnostic Interview Schedule
@IS).‘3J4 and there was no other signiticant medical
comorbidity 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 disorder
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 temporal relationship to the use of medications such as
sympathomimetic agents, vasodilatom, anticholinergics, 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 justify causality, similar to previous reports on adverse
drug reactions. l6
Definite: (1) Palpitations following a temporal sequence after the medication was introduced or
reached an abnormal level, (2) resolving after withdrawal of the medication or normalization of the
1996 The American Journal of Medicine@ Volume 100
PATIENTS WITH PALPITATIONS/WEBER AND KAPOOR
blood concentration, and (3) having no other apparent 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 relationship to the use of cocaine17-1g and amphetamines,15 caffeine,2@23 and nicotine15 have been reported. Criteria have been developed to define this
association.
0 Cocaine or amphetamines
Definite: (1) Palpitations temporally related to cocaine or amphetamine use, (2) with resolution after
discontinuation of the drug, and (3) no other apparent etiology.
Probable: Palpitations temporally related to cocaine or amphetamine use and one of the other two
factors listed above.
Possible: Palpitations temporally related to cocaine or amphetamine use, but other possible etiologies exist.
0 Caffeine
Definite: (1) Palpitations temporally related to caffeine intake of greater than 4 cups of coffee (or equivalent) per day, (2) with resolution after discontinuation of caffeine, and (3) no other apparent etiology.
Probable: Palpitations temporally 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 temporally related to any caffeine intake, but other possible etiologies exist.
0 Nicotine
Definite: (1) Palpitations temporally related to
nicotine product use, (2) with resolution after cessation, and (3) no other apparent etiology.
Probable: Palpitations temporally related to nicotine product use and one of the other two factors
listed above.
Possible: Palpitations temporalIy related to nicotine product use, but other possible etiologies exist.
Metabolic
Disorders.
Several metabolic disorders have been reported to be associated with palpitations and are often accompanied by a sinus tachycardia. 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 associated
with the clinical presence of thyrotoxicosis,
confirmed by laboratory tests.
0 Pheochromocytoma. 26 Palpitations were associated with the clinical presence of pheochromocytoma, confiied
by laboratory tests.
l Mastocytosis. 27Palpitations were associated with
the clinical presence of mastocytosis, confirmed by
laboratory tests.
l Scombroid food poison&g.2x Palpitations following ingestion of scombroid fish.
0 Idiopathic flushing. 2g The clinical scenario was
consistent with idiopaQic flushing and other disorders 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
comorbidity 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 palpitations 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 considered causal when palpitations were temporally related 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 believed to
be related to a physiologic (compensatory) sinus
tachycardia. These were considered present in the appropriate clinical setting if clinical or laboratory signs
of dehydration or symptomatic orthostatic hypotension 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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