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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,

138 February 1996 The American Journal of Medicine” 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 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-

February 1996 The American Journal of Medicinea Volume 100

139



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-

140 February 1996 The American Journal of Medicine* Volume 100



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

February 1996 The American Journal of Medicine’ Volume X00

141



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-

142 February 1996 The American Journal of Medicine” Volume 100



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.

February 1996 The American Journal of Medicinea Volume

100

143



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

144 February 1996 The American Journal of Medicine@ Volume 100



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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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.

1988;45:62-63.

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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




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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