The Impact of Atrial Fibrillation Clinical Subtype on Mortality

JACC: CLINICAL ELECTROPHYSIOLOGY

VOL.

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

-, NO. -, 2017

ISSN 2405-500X/$36.00

PUBLISHED BY ELSEVIER

https://doi.org/10.1016/j.jacep.2017.09.002

The Impact of Atrial Fibrillation Clinical Subtype on Mortality Melissa Leung, MBBS, BSC(MED), MBIOSTAT, PHD,a,b Philippe J. van Rosendael, MD,a Rachid Abou, MD,a Nina Ajmone Marsan, MD, PHD,a Dominic Y. Leung, MBBS, PHD,b Victoria Delgado, MD, PHD,a Jeroen J. Bax, MD, PHDa

ABSTRACT OBJECTIVES This study sought to investigate the prognostic implications of the clinical subtype of atrial fibrillation (AF): paroxysmal or persistent. BACKGROUND Underlying structural abnormalities of the left atrium may be responsible for the initial clinical presentation of AF in either paroxysmal or persistent form, yet the prognostic implications of the clinical subtype on presentation are unknown. METHODS Over a median of 7 years, 1,773 patients (age 64
12 years, 74% males) with nonvalvular AF with index presentations for paroxysmal or persistent AF were followed for the occurrence of all-cause mortality. Clinical information including cardiovascular risk factors, comorbid diseases associated with AF, and CHA2DS2-VASc (congestive heart failure, hypertension, age $75 [double weight], diabetes, stroke [double weight], vascular disease, age 65–74, and sex category [female]) score was collected and analyzed. RESULTS In this study, 1,005 patients (57%) had persistent AF. Eighty patients (10%) with paroxysmal AF and 174 patients (17%) with persistent AF died during the follow-up period. Persistent AF compared with paroxysmal AF upon initial AF diagnosis was independently associated with worse survival independent of the CHA2DS2-VASc score and other high-risk cardiovascular risk factors (hazard ratio: 1.24; 95% confidence interval: 1.11 to 1.38). CONCLUSIONS In patients with nonvalvular AF, persistent AF compared with paroxysmal AF upon first diagnosis is independently associated with increased mortality. (J Am Coll Cardiol EP 2017;-:-–-) © 2017 by the American College of Cardiology Foundation.

A

trial fibrillation (AF) is the leading cause of

developing incident AF, and one-third of AF patients

cardiovascular disease worldwide (1), with a

experiencing

prevalence increasing in both developed

remained unclear whether AF is associated with mor-

incident

heart

failure

(5).

It

has

and developing countries (2). AF is an independent

tality independent of the coexisting conditions with

predictor of all-cause mortality, associated with a

which it is often observed (3). Studies examining the

2-fold adjusted increase in death (3). The cardiovas-

prognostic implications of clinical subtype in a large

cular deaths associated with AF result from progres-

general population of patients with AF have been

sive heart failure and sudden death (4). A recent

limited by inclusion of prevalent AF (6–9), small

large observational study demonstrated a bidirec-

numbers of AF patients (7,8,10,11), or a lack of clarifi-

tional relationship between AF and heart failure,

cation of the independent impact of AF on mortality

with approximately 50% of heart failure patients

in multivariate or time-dependent analyses (6,8–11).

From the aDepartment of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands; and the bDepartment of Cardiology, Ingham Institute at Liverpool Hospital, University of New South Wales, Sydney, Australia. The Department of Cardiology at Leiden University Medical Center has received unrestricted research grants from Biotronik, Boston Scientific, Medtronic, and Edwards Lifesciences. Dr. M. Leung has received a Pfizer Investigator Initiated Research Grant. Dr. Delgado has received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received June 27, 2017; revised manuscript received August 24, 2017, accepted September 7, 2017.

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Atrial Fibrillation Subtype and Mortality

ABBREVIATIONS

In patients with AF, the use of beta-blockers

(congestive heart failure, hypertension, age $75

AND ACRONYMS

and statins has been associated with a better

[double weight], diabetes, stroke [double weight],

prognosis, and the presence of myocardial

vascular

dysfunction, heart failure, and concomitant

[female]) was additionally calculated for each patient

AF = atrial fibrillation CHADS2 = congestive heart

disease,

age

65–74,

and sex category

chronic kidney disease have been associated

based on a point system in which 2 points were

diabetes, stroke (double

with a worse prognosis (12–20). It remains

assigned for a history of stroke or transient ischemic

weight)

unclear whether the clinical subtype of AF—

attack, or age $75 years; and 1 point each was

CHA2DS2-VASc = congestive

paroxysmal or persistent—has any impact on

assigned for age 65–74 years, a history of hyperten-

heart failure, hypertension,

failure, hypertension, age ‡75,

mortality. We hypothesized that the clinical

sion, diabetes, cardiac failure, or vascular disease

diabetes, stroke (double

subtype of AF may have a differential impact

(myocardial infarction, peripheral artery disease,

weight), vascular disease, age

on all-cause mortality.

complex aortic plaque), and female sex (22). Labora-

age ‡75 (double weight),

65–74, and sex category

tory parameters, such as serum creatinine, total

(female)

METHODS

CI = confidence interval

cholesterol,

triglycerides,

and

thyroid

hormone

levels, were recorded. Left ventricular ejection frac-

HR = hazard ratio

PATIENTS. Patients in this study were iden-

tion was measured from two-dimensional echocar-

tified from a database of all patients who were sub-

diographic images on apical 4- and 2-chamber views

sequently referred to our tertiary referral center for

using Simpson’s biplane method of discs (23). The

electrical cardioversion for AF from June 2005 until

Institutional Review Board approved this retrospec-

January 2015. The first admission (including visits to

tive analysis of clinically acquired data and waived

the emergency department or hospital admission)

the need for written informed consent.

with AF for all such patients was identified. The AF subtype was then classified, and the clinical details were collected based on chart review from the time of their first admission. AF was diagnosed in accordance with the European Society of Cardiology guidelines for the management of AF (21). The patients were classified into 2 groups: paroxysmal AF or persistent AF. Paroxysmal AF was defined

as

self-terminating

AF,

usually

within

48 hours, with paroxysms continuing for up to a

CLINICAL

ENDPOINT

AND

FOLLOW-UP. Patients

were followed by electronic chart review for the clinical endpoint of all-cause mortality. All-cause mortality was defined as death from any cause. Deceased patients were identified from the hospital medical records (EPD-Vision and EZIS, Leiden University Medical Centre, Leiden, the Netherlands). This information system is linked to the national death registry and updated on a monthly basis.

maximum of 7 days. Persistent AF was defined as

STATISTICAL ANALYSIS. Continuous variables are

recurrent AF that was not self-terminating, with an

presented as mean
SD for normally distributed

episode lasting >7 days or requiring termination by

variables, and median (interquartile difference) for

either electrical or pharmacological cardioversion.

non-Gaussian variables. Continuous variables were

Permanent AF was defined as AF with the accepted

compared with the unpaired Student t test, and Wil-

rhythm and rhythm control strategies no longer pur-

coxon rank sum test, as appropriate. Categorical data

sued. The patients with persistent or permanent AF

are summarized as frequencies and percentages, and

were grouped together for the purposes of the present

are compared using the chi-square test. Kaplan-Meier

study. For both the paroxysmal and persistent AF

survival curves were constructed for the primary

groups the patients were required to have had no

endpoint of all-cause mortality, with log-rank testing

prior documentation of AF by clinical examination,

for statistical significance between strata. Multivari-

electrocardiography, or device monitoring. Patients

able Cox regression analysis was performed to iden-

with a history of palpitations before the initial diag-

tify

nosis of AF, mechanical heart valves, or mitral ste-

all-cause mortality. Hazard ratios (HRs) and 95%

nosis were excluded. A total of 1,773 patients were

confidence intervals (CIs) are provided.

included in the present study and then followed-up with the index AF as time point 0.

the

factors

independently

associated

with

Clinical and echocardiographic parameters were chosen a priori based on biological plausibility and

Clinical information including demographic data,

published studies (5,12–14,24). Case elimination was

medications, cardiac risk factors (hypertension, dia-

used for missing data, whereby a patient was

betes mellitus, dyslipidemia, smoking history), co-

excluded from analyses when that variable was used

morbid medical conditions such as coronary artery,

if data were missing for a particular variable. In

pulmonary, and thyroid disease, and history of heart

addition, propensity analysis was performed creating

failure were collected. The CHA 2DS2 -VASc score

two groups of patients matched for age, sex, body

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Atrial Fibrillation Subtype and Mortality

mass index, CHA2DS 2-VASc score, and left ventricular ejection fraction (see the Online Appendix, Table 1). A

T A B L E 1 Clinical Characteristics of Patients by Type of Atrial Fibrillation at

Time of First Diagnosis

2-tailed p < 0.05 was considered statistically signifi-

Paroxysmal AF (n ¼ 768)

cant. Statistical analyses were performed using STATA version 12 (STATACorp, College Station, Texas).

Persistent AF (n ¼ 1,005)

p Value

<0.001

Clinical features Age (yrs)

62
13

66
11

Male

561 (73)

752 (75)

0.397

RESULTS

Body mass index (kg/m2)

27.4
4

26.9
5

0.027

58 (15)

52 (20)

<0.001

CLINICAL

CHA2DS2-VASc score

2 (2)

3 (3)

<0.001

Requirement for subsequent electrical cardioversion

435 (57%)

562 (56%)

0.635

Requirement for subsequent radiofrequency catheter ablation

243 (32%)

278 (28%)

0.070

Left ventricular ejection fraction (%)

CHARACTERISTICS. A

total

of

1,773

patients with nonvalvular AF were followed over a median of 7.0 years (interquartile difference 7.1 years). The mean age of the population was 64
12 years, with 1,312 males (74%). There were 1,005 patients (57%) in the study population with persistent AF. Patients with persistent AF were older, had a larger body mass index, a higher prevalence of hypertension, moderate or severe left-

Cardiac risk factors Hypertension

506 (66)

737 (73)

0.001

Current smoker

126 (16)

150 (15)

0.399

Dyslipidemia

369 (48)

505 (50)

0.358

97 (13)

155 (15)

0.095 0.032

Diabetes mellitus Other medical conditions

sided valvular heart disease and pulmonary disease,

Pulmonary disease

111 (14)

184 (18)

worse left ventricular ejection fraction, and greater

Obstructive sleep apnea

11 (1)

28 (3)

0.052

use of angiotensin-converting enzyme inhibitors or

Hyperthyroidism

28 (4)

46 (5)

0.331

Coronary artery disease

255 (33)

369 (37)

0.125

Coronary bypass surgery

114 (15)

168 (17)

0.285

Percutaneous coronary intervention

138 (18)

180 (18)

0.975

(Table 1). In addition, patients with persistent AF

Previous myocardial infarction

155 (20)

248 (25)

0.026

had a higher median CHA 2 DS2-VASc score and greater

History of heart failure

177 (23)

383 (38)

<0.001

use of anticoagulants compared with the patients

Previous TIA or stroke

71 (9)

91 (9)

who had paroxysmal AF. No other differences were

$ Moderate left-sided valvular heart disease

90 (12)

164 (16)

0.006

observed between the patients with persistent AF and

Implantable cardiac defibrillator

72 (9)

194 (19)

<0.001

Cardiac resynchronization therapy

37 (5)

115 (11)

<0.001

angiotensin II receptor blockers and beta-blockers compared with the patients who had paroxysmal AF

those with paroxysmal AF. The requirement for subsequent electrical cardioversion or radiofrequency catheter ablation were not different between the

0.891

Medications Aspirin or clopidogrel

236 (31)

120 (12)

<0.001

Anticoagulant (warfarin or NOAC)

345 (45)

902 (90)

<0.001

patients with paroxysmal compared with persistent

ACEi or ARB

382 (50)

636 (63)

<0.001

AF, respectively.

Beta-blocker

461 (60)

760 (76)

<0.001

Calcium channel blocker

147 (19)

210 (21)

0.368

50 (7)

124 (12)

<0.001

OUTCOMES. A total of 254 patients (14%) met the

Amiodarone

primary endpoint of all-cause mortality. The baseline

Sotalol

179 (23)

214 (21)

clinical characteristics of the patients according to

Flecainide

88 (11)

38 (4)

<0.001

mortality status at the end of the follow-up period are

Propafenone

8 (1)

2 (0.2)

0.024

presented in Table 2. The patients who died were

Disopyramide

6 (0.8)

2 (0.2)

older, with a higher prevalence of smoking, dyslipi-

Diuretic

203 (26)

432 (43)

<0.001

63 (8)

148 (15)

<0.001

335 (44)

467 (46)

0.242

demia, and diabetes mellitus compared with the patients who survived. The prevalence of hyperthy-

Aldosterone antagonist Statin

0.305

0.084

roidism was similar between the two groups; how-

Values are mean
SD median (interquartile difference) or n (%).

ever, the rates of pulmonary disease, coronary artery

ACEi ¼ angiotensin converting enzyme inhibitor; ARB ¼ angiotensin II receptor blocker; CHA2DS2-VASc ¼ congestive heart failure, hypertension, age $75 (double weight), diabetes, stroke (double weight), vascular disease, age 65–74, and sex category (female); NOAC ¼ novel anticoagulant; TIA ¼ transient ischemic attack.

disease, heart failure, stroke, significant left-sided valvular heart disease, and implantable cardiac defibrillator use were higher in those who died. However, the patients who died had higher use of anticoagu-

similar. Furthermore, use of diuretics was higher in

lants, angiotensin-converting enzyme inhibitors, or

the patients who died, reflecting the higher preva-

angiotensin II receptor blockers, amiodarone, miner-

lence of heart failure in this group. In regard to lab-

alocorticoid receptor antagonists, and statins, and

oratory parameters, serum creatinine levels were

lesser use of flecainide compared with their counter-

higher while the hemoglobin and total cholesterol

parts. The use of other antiarrhythmic drugs was

levels were lower in those who died.

Leung et al.

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Atrial Fibrillation Subtype and Mortality

T A B L E 2 Clinical Characteristics of Patients at the Time of First Diagnosis of Atrial

Fibrillation by Mortality Status

factors known to influence mortality in patients with AF, including the CHA 2DS 2-VASc score, incorporated as covariates in the model (Table 3). The presence of

Alive (n ¼ 1,519)

Dead (n ¼ 254)

p Value

63
12

71
9

<0.001

1,121 (74)

191 (75)

0.638

Body mass index (kg/m2)

27
5

27
5

0.063

When we evaluated the association between the

Left ventricular ejection fraction (%)

53
13

45
14

<0.001

type of AF and all-cause mortality in a propensity

1,055 (69)

189 (74)

0.107

Current smoker

213 (14)

63 (25)

<0.001

Dyslipidemia

709 (47)

166 (65)

<0.001

Diabetes mellitus

181 (12)

71 (28)

<0.001

224 (15)

71 (28)

<0.001

67 (4)

7 (3)

Coronary artery disease

467 (31)

157 (62)

<0.001

Coronary bypass surgery

203 (13)

79 (31)

<0.001

first AF diagnosis was independently associated with

Clinical features Age (yrs) Male

persistent AF compared with paroxysmal AF upon

Cardiac risk factors

worse survival independent of the CHA 2DS2-VASc score (HR: 1.24; 95% CI: 1.11 to 1.38).

analysis, the patients with persistent AF had higher

Hypertension

Hyperthyroidism

with paroxysmal AF (Figure 1). On multivariable analysis, the type of AF was still independently associated with all-cause mortality (persistent AF vs.

Other medical conditions Pulmonary disease

cumulative event rates as compared with the patients

0.223

paroxysmal AF; HR: 2.19; 95% CI: 1.072 to 4.476; p ¼ 0.032) (Online Appendix, Table 2). A secondary analysis explored the differential impact of persistent compared with permanent AF on

Percutaneous coronary intervention

238 (16)

80 (32)

<0.001

Previous myocardial infarction

289 (19)

114 (45)

<0.001

History of heart failure

392 (26)

168 (66)

<0.001

(n ¼ 9), in view of a previous finding that permanent

Previous TIA or stroke

130 (9)

33 (13)

0.023

AF was associated with higher mortality than parox-

$ Moderate left-sided valvular heart disease

205 (13)

49 (19)

0.014

ysmal AF (25). Persistent AF compared with parox-

Implantable cardiac defibrillator

181 (12)

85 (33)

<0.001

ysmal AF remained an independent correlate of

Cardiac resynchronization therapy

94 (6)

58 (23)

<0.001

worse survival in a multivariable model controlling

84 (24)

103 (51)

<0.001

TSH (mU/l)

1.92 (1.73)

2.14 (2.02)

0.087

T4 (pmol/l)

17.1 (3.7)

17.1 (4.4)

0.437 <0.001

Laboratory characteristics Creatinine (mmol/l)

survival, excluding the patients with permanent AF

for the same covariates (HR: 1.54; 95% CI: 1.13 to 2.08; p ¼ 0.006) (Online Appendix, Table 3).

DISCUSSION

Total cholesterol (mmol/l)

5.0
1.2

4.6
1.3

Triglycerides (mmol/l)

1.51 (1.12)

1.42 (0.86)

Hemoglobin (mmol/l)

8.8
1.2

8.2
1.2

302 (20)

54 (21)

0.588

with paroxysmal AF—in a large population with non-

1,056 (69)

192 (76)

0.038

ACEi or ARB

852 (56)

166 (66)

0.004

valvular AF upon first diagnosis was independently

Beta-blocker

708 (47)

120 (47)

0.808

Calcium channel blocker

312 (21)

46 (18)

0.390

0.075 <0.001

Medications

The present study demonstrated that the prognostic value of AF clinical subtype—persistent compared

Aspirin or clopidogrel Anticoagulant (warfarin or NOAC)

associated with worse survival, after adjusting for factors known to influence mortality.

Amiodarone

136 (9)

38 (15)

0.003

Sotalol

337 (22)

56 (22)

0.986

Flecainide

123 (8.1)

3 (1.2)

<0.001

Propafenone

9 (0.6)

1 (0.4)

1.000

Disopyramide

7 (0.5)

1 (0.4)

1.000

studies of patients with implantable cardiac devices

Diuretic

472 (31)

163 (64)

<0.001

(26–30). Recently, in a small study of patients with AF

Aldosterone antagonist

134 (9)

77 (30)

<0.001

undergoing transcatheter aortic valve implantation,

Statin

472 (31)

163 (64)

<0.001

the presence of persistent AF was associated with a

Values are mean
SD, median (interquartile difference) or n (%). T4 ¼ thyroxine; TSH ¼ thyroid-stimulating hormone; other abbreviations as in Table 1.

AF CLINICAL SUBTYPE AND PROGNOSTIC INDICATORS.

The value of AF subtype for predicting cerebrovascular events has previously been shown in multiple

higher cumulative risk of stroke or death at 2 years compared with the presence of paroxysmal AF or sinus rhythm (31). In a Swedish registry of 155,071 patients with acute myocardial infarction, the com-

COMPARISON BETWEEN AF SUBTYPES. Significantly

posite outcome of all-cause mortality, myocardial

more patients with persistent AF than paroxysmal AF

infarction,

died during the follow-up period (17% vs. 10%,

compared in four subtypes of AF (new onset AF with

respectively; p < 0.001). To estimate the excess

sinus rhythm at discharge, new onset AF with AF at

mortality attributable to AF clinical subtype, we per-

discharge, paroxysmal AF, and chronic AF) with the

formed multivariable Cox regression analyses with

patients in sinus rhythm (32). The investigators

or

ischemic

stroke

at

90-days

was

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demonstrated that all subtypes of AF were associated with a higher risk of the composite endpoint when these patients were compared with the patients in

T A B L E 3 Cox Regression Model Examining the Association Between AF Subtype and

All-Cause Mortality, Adjusting for CHA 2 DS 2 -VASc Score, Traditional Cardiac Risk Factors, Treatment, and Comorbid Medical Conditions

sinus rhythm, but there were no major differences

Multivariable Analysis

between the AF subtypes. Previous studies examining the prognostic implications of AF subtypes (paroxysmal versus persistent)

5

Atrial Fibrillation Subtype and Mortality

HR (95% CI)

p Value

Persistent vs. paroxysmal AF

1.24 (1.11, 1.38)

<0.001

CHA2DS2-VASc score

1.03 (1.00, 1.07)

0.048

have mainly focused on stroke and other adverse

Body mass index (kg/m2)

1.01 (1.00, 1.02)

0.160

cardiovascular events. The limited studies that have

Left ventricular ejection fraction (%)

examined the relationship between AF clinical sub-

Current smoker

type and mortality have differed in their inclusion

Dyslipidemia

1.12 (0.96, 1.29)

of prevalent rather than incident AF (6–9), their

Pulmonary disease

1.28 (1.12, 1.47)

small numbers of AF patients (7,8,10,11), their exclusion of patients with AF at baseline, or their lack

0.99 (0.99, 1.00)

0.002

1.12 (0.98, 1.28)

Hyperthyroidism

0.111 0.140 <0.001

0.80 (0.63, 1.01)

$ Moderate left-sided valvular heart disease Use of beta-blockers

0.063

1.13 (0.98, 1.29)

0.090

1.08 (0.98, 1.21)

0.134

of adjustment for known high-risk parameters such

Use of statins

0.97 (0.84, 1.12)

as the CHA2DS2-VASc score in multivariate or time-

Use of anticoagulants

0.70 (0.62, 0.79)

<0.001

dependent analyses (6,8–11). Our present study

Serum creatinine, per 10 mmol/l

1.01 (1.00, 1.02)

0.073

LR chi-square (13) ¼ 114.8, p < 0.001

demonstrates a relationship of AF subtype with increased mortality in patients with incident AF after adjustment for known high-risk parameters. The clinical scores CHA2DS 2-VASc and CHADS 2 (congestive heart failure, hypertension, age $75,

0.661

For continuous variables, hazard ratios refer to a 1-U increase in the independent variable except where specified otherwise. For CHA2DS2-VASc score, the hazard ratio refers to a one point increase in the score. AF ¼ atrial fibrillation; CHA2DS2-VASc ¼ congestive heart failure, hypertension, age $75 (double weight), diabetes, stroke (double weight), vascular disease, age 65–74, and sex category (female); CI ¼ confidence interval; HR ¼ hazard ratio; LR ¼ likelihood ratio.

diabetes, stroke [double weight]) have been widely used in stroke risk stratification. More recently, there has been growing interest in examining the prog-

The subsequent management of our patients was not

nostic value of the CHA 2DS2-VASc score in patients

controlled, yet we demonstrated the independent

without AF. MOST (Mode Selection Trial) examined

prognostic value of the AF subtype at first presenta-

the predictive value of CHA2 DS2-VASc and CHADS 2

tion. Together with the similar requirements for

scores for the individual and composite outcomes of

subsequent

death or stroke in 2,010 patients with pacemakers for

frequency catheter ablation, this may suggest that

electrical

cardioversion

and

radio-

sinus node dysfunction (33). Each 1 point increase in the CHA2DS2-VASc or CHADS2 scores was associated with an increase in the HR for the combined endpoint of death or stroke, and was independent of a previous history of AF. A proposed explanation for the relationship of CHA2 DS2-VASc and CHADS 2 scores with cardiovascular events and mortality independent of AF is that the individual components of these scores (e.g., diabetes, hypertension, coronary artery disease, and heart failure) constitute risk markers for vascular events that include, but are not limited to, stroke. Patients who died in our cohort had higher CHA 2DS2-VASc scores and an increased prevalence of diabetes and heart failure. Furthermore, our study demonstrated that the diagnosis of persistent as opposed to paroxysmal AF as a worse prognostic marker is independent of the risk measured by the CHA2DS 2-VASc score. The demonstration of higher mortality in patients with persistent AF compared with paroxysmal AF at the onset of diagnosis is supported by the findings that patients with persistent AF showed distinct electrophysiological properties and AF drivers indicative of diffuse biatrial substrate disease (34).

F I G U R E 1 Kaplan-Meier Survival Estimates in a Propensity Matched Analysis for

All-Cause Mortality by AF Subtype

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Atrial Fibrillation Subtype and Mortality

the prognostic implications of persistent versus

CONCLUSIONS

paroxysmal AF may be independent of any subsequent management of AF. STUDY

LIMITATIONS. Our

In a large population of patients with nonvalvular AF, study was performed

retrospectively and was designed to examine whether the clinical subtype of AF upon initial diagnosis—as distinct from the lifetime burden of AF after diagnosis—bears any significance for prognosis. In view of this, no monitoring of patients by Holter or device (loop recorder, pacemaker, or implantable cardiac defibrillator) was performed after the initial

the presence of persistent AF compared with paroxysmal AF upon first diagnosis was independently associated with increased mortality. ADDRESS FOR CORRESPONDENCE: Dr. Jeroen J.

Bax, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. E-mail: [email protected].

diagnosis of AF. The impact of the latter, in particular with frequent, recurrent, short-lived paroxysms, on mortality would also be of interest in future prospectively designed studies. However, in practice, most patients with AF do not receive electronic device monitoring, so the burden of disease is largely determined by patient history and clinical presentation. Our study explores this from a practical perspective. Clinical data were collected from the patient’s initial presentation with AF to our institution, not necessarily during the patient’s admission for cardioversion. Although these patients eventually were referred for electrical cardioversion, it may not have occurred during their initial presentation; the patients may have spontaneously reverted before having the procedure performed. Hence, our patient population is representative of a general population of AF patients presenting at the hospital, with the exception of AF patients who did not require cardio-

PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: Atrial fibrillation is an independent predictor of all-cause mortality. The cardiovascular deaths that AF is associated with result from progressive heart failure and sudden death. TRANSLATIONAL OUTLOOK: In patients with nonvalvular AF, persistent AF compared with paroxysmal AF upon first diagnosis is independently associated with increased mortality and is incremental to the risk measured by the CHA2DS2-VASc score. Together with the similar requirement for subsequent electrical cardioversion and radiofrequency catheter ablation in these patients, this may suggest that the prognostic implications of persistent versus paroxysmal AF may be independent of any subsequent management of AF.

version during the follow-up period.

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KEY WORDS atrial fibrillation, mortality, prognosis

30. Boriani G, Glotzer TV, Santini M, et al.

A PP END IX For supplemental material and tables, please see the online version of this

Device-detected atrial fibrillation and risk for

paper.

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