- Email: [email protected]
Atrial Fibrillation in Heart Failure∗
JACC: HEART FAILURE
VOL.
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
-, NO. -, 2017
ISSN 2213-1779/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jchf.2017.05.010
EDITORIAL COMMENT
Atrial Fibrillation in Heart Failure* A Common and Deadly Combination Carolyn S.P. Lam, MBBS, PHD,a,b Bernadet T. Santema, MD,b Adriaan A. Voors MD, PHDb
A
trial fibrillation (AF) and heart failure (HF)
This analysis was accomplished using the nationwide
are global cardiovascular epidemics that are
Swedish HF Registry of 41,446 patients with clinician-
inextricably linked to each other and to pop-
judged HF, linked to the National Patient Registry for
ulation aging. Prior studies have established that AF
additional data on comorbidities, HF hospitalization,
is both a risk marker and risk factor in HF, resulting
and stroke or transient ischemic attack, as well as the
from, causing, and/or adversely impacting outcomes
National Population Registry for date of death and
in HF. Most prior studies focused on HF with reduced
Statistics Sweden for socioeconomic data. The most
ejection fraction (HFrEF), where the emphasis was on
striking finding was the very high prevalence of AF:
neurohormonal activation and hemodynamic mecha-
53% in HFrEF, 60% in HFmrEF, and 65% in HFpEF
nisms perpetuating the HFrEF–AF vicious cycle. In
(Table 1). The broad inclusion of AF, defined as having
contrast, in HF with preserved EF (HFpEF), at present
a history of AF (in either the Swedish HF or National
the dominant form of HF in the United States, the
Patient Registry) or AF on electrocardiography, may
focus is on systemic inflammation and shared risk
partially explain the high prevalence. Indeed, prior
factors for both AF and HFpEF (such as aging, hyper-
studies that similarly used International Classifica-
tension, and obesity) (1). Thus, given potential differ-
tion of Diseases-Ninth Revision-Clinical Modification
ences in pathogenesis, AF may relate differently to
codes to define their AF population reported higher
HFrEF versus HFpEF; however, few studies made
prevalence of AF compared with those that used the
this comparison within the same cohort (Table 1).
electrocardiographic diagnosis (Table 1). Another
Furthermore, no prior study has examined AF in HF
explanation may be the unselected population-wide
with midrange EF (HFmrEF).
approach used in the Swedish HF cohort, which
The paper by Sartipy et al. (2) in this issue of JACC:
included patients at an advanced age. In fact, age
Heart Failure is noteworthy for being one of the
above the median of 76 years old was the strongest
largest single population-based cohorts to systemat-
risk factor for AF, more than doubling the odds of AF
ically compare AF versus sinus rhythm across the
in HF regardless of EF.
entire EF spectrum of HF, including, for the first time,
The increasing prevalence of AF with increasing
patients with HFmrEF as a distinct category (Table 1).
EF deserves further consideration. Age may be the simplest explanation for the differences between EF groups, because HFpEF patients were oldest, HFrEF
*Editorials published in JACC: Heart Failure reflect the views of the au-
youngest,
thors and do not necessarily represent the views of JACC: Heart Failure or
Figure 1 in Sartipy et al. (2) showed that at any
the American College of Cardiology.
given age the prevalence of AF was still higher in
From the aNational Heart Center Singapore, Singapore and Duke-National
HFpEF and, if anything, the difference in AF prev-
University of Singapore, Singapore; and the bDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Gronin-
and
HFmrEF
in
between.
However,
alence among HF groups widened with advancing
gen, the Netherlands. Dr. Lam has reported that she has received research
age. Beyond age, Sartipy et al. (2) also showed that
support from Boston Scientific, Bayer, Thermofisher, Medtronic, and
male sex, longer duration of HF, nonischemic eti-
Vifor Pharma; and served as a consultant for Bayer, Novartis, Takeda,
ology, and prior stroke independently increased the
Merck, Astra Zeneca, Janssen Research & Development, LLC, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Stealth BioTherapeutics,
odds of AF. The commonality of these risk factors to
Covia, Roche, and Magen. All other authors have reported that they have
HFpEF, HFmrEF, and HFrEF suggests that the HF
no relationships relevant to the contents of this paper to disclose.
syndrome per se is most strongly related to AF risk,
2
Lam et al.
JACC: HEART FAILURE VOL.
-, NO. -, 2017 - 2017:-–-
Atrial Fibrillation in Heart Failure
T A B L E 1 Real-World Cohorts With Both HFpEF and HFrEF, Comparing AF vs. Sinus Rhythm or Non-AF
Design/study
Sample Size
%HFpEF/HFmrEF/ HFrEF
LVEF cutoff %
Swedish Heart Failure Registry
41,446
23/22/55
$50 vs.
SR 74.4 12.5 AF 79.1 9.0
SR 44 AF 46
40-49 vs.
SR 70.7 13.1 AF 76.8 9.9
SR 61 AF 60
#39
SR 68.8 13.4 AF 74.3 10.7
SR 68 AF 73
$40 vs.
Non-AF 78.9 8.0 AF 80.8 7.4
Non-AF 33 AF 37
<40
Non-AF 77.6 7.6 AF 78.8 7.3
Non-AF 55 AF 61
$50 vs.
SR 71.6 8.4 AF 73.8 8.9
SR 36 AF 21
<50
SR 61.5 8.4 AF 63.0 7.1
SR 71 AF 63
Overall: Non-AF 71.6 13.1 Pre-existing AF 77.5 10.2
Overall: Non-AF 52 Pre-existing AF 52
First Author, Year (Ref. #)
Sartipy, 2017 (2)
Eapen, 2014 (3)
Retrospective, ADHERE-Core
Fung, 2007 (4)
66,357
Prospective, single center
McManus, 2013 (5)
238
Retrospective cohort
23,644
55/0/45
61/0/39
$50 vs.
60/0/40
#40 Santhanakrishnan, 2016 (6) Shamagian, 2006 (7)
Framingham Heart Study
1,166
Retrospective cohort
1,636
41/0/44 40/0/60
Age, mean SD
Sex, % Male
$45 vs.
Overall 79 11
Overall 41
<45
Overall 77 10
Overall 66
$50 vs.
Non-AF 72.7 10.6 AF 71.6 9.4
Non-AF 51 AF 46
<50
Non-AF 67.4 12.5 AF 67.5 11.3
Non-AF 69 AF 71
T A B L E 1 Continued
First Author, Year (Ref. #)
Definition AF
Sartipy, 2017 (2)
History of AF or AF on any ECG
Eapen, 2014 (3)
History of AF or ICD-9-CM code at baseline
Fung, 2007 (4)
AF on baseline ECG
McManus, 2013 (5)
ICD-9-CM code
Control (SR or Non-AF)
Clinical Correlates of AF
Outcome in AF Compared With Control (95% CI)
HFpEF 65% HFmrEF 60% HFrEF 53%
Age, male, no prior MI, duration of HF, prior stroke/TIA
HF hospitalization or death HFpEF: HR 1.17 (1.09–1.26) HFmrEF: HR 1.29 (1.20–1.40) HFrEF: HR 1.15 (1.10–1.20)
Non-AF
HFpEF 47.6% HFrEF 44.2%
Age, male, no prior MI, no DM, prior stroke/TIA
30-day mortality HFpEF: HR 1.16 (1.08–1.25) HFrEF: HR 1.00 (0.94–1.08)
SR
HFpEF 28.8% HFrEF 32.6%
Previous HF hospitalization, lower QoL
HF hospitalization or death HFpEF: HR 3.1 (1.6–5.2)
Non-AF
HFpEF 52.7% HFrEF 41.9%
Age, male, no prior MI, valvular disease
Mortality (pre-existing AF) HFpEF: HR 1.11 (1.03–1.20) HFrEF: HR 1.15 (1.05–1.26)
Santhanakrishnan, 2016 (6) Prevalent, concurrent or future AF on any ECG or hospital record
Non-AF
HFpEF 32% prevalent (18% concurrent, 12% future) HFrEF 23% prevalent (18% concurrent, 13% future)
No prior MI, no DM, preserved LVEF
Mortality (prevalent HF) New-onset AF HFpEF: HR 1.83 (1.41–2.37) HFrEF: HR 2.72 (2.12–3.48)
Shamagian, 2006 (7)
Non-AF
HFpEF 38.7% HFrEF 31.0%
No DM, nonischemic etiology, more peripheral edema, preserved LVEF
Mortality—HFpEF: no difference, Log rank 0.204 HFrEF: RR 1.83 (1.12–2.99)
AF on baseline ECG
SR
Prevalence AF
ADHERE ¼ Acute Decompensated Heart Failure National Registry; AF ¼ atrial fibrillation; DM ¼ diabetes mellitus; ECG ¼ electrocardiogram; HF ¼ heart failure; HFpEF ¼ heart failure with preserved ejection fraction; HFmrEF ¼ heart failure with mid-range ejection fraction; HFrEF ¼ heart failure with reduced ejection fraction; HR ¼ hazard ratio; ICD-9-CM ¼ International Classification of DiseasesNinth Revision-Clinical Modification; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; RR ¼ relative risk; QoL ¼ quality of life score; SR ¼ sinus rhythm; TIA ¼ transient ischemic attack.
rather than potential different mechanisms among
Another potential explanation for the highest
the HF types. The greatest prevalence of AF in
prevalence of AF in the HFpEF group is misclassifi-
HFpEF would then imply that patients with HFpEF
cation of patients with symptomatic AF, but without
had the most severe HF, and indeed these patients
true HF, as HFpEF. The inclusion criterion of patients
had the worst outcomes, even when looking only at
with clinician-judged HF in the Swedish HF Registry
patients in sinus rhythm, compared with HFrEF and
is highly relevant, because clinical judgement of HF
HFmrEF.
depends on classic symptomatology (breathlessness,
JACC: HEART FAILURE VOL.
-, NO. -, 2017
Lam et al.
- 2017:-–-
Atrial Fibrillation in Heart Failure
exertional intolerance), which overlaps with that of
biomarkers, or panels of biomarkers, may be useful
AF. Furthermore, diastolic function is challenging to
diagnostically, but require testing in cohorts of iso-
determine by echocardiography in the presence of
lated AF versus combined AF with HF (invasively
AF, and AF alone (without HF) is associated with
proven). The predisposition of men to AF in HF
increased N-terminal pro-B type natriuretic peptide
compared with women, and relative “protective”
(NT-proBNP) (1). However, one would expect better
effect of diabetes against AF in HFpEF (but not in
outcomes in patients with pure AF without HF, yet
HFrEF or HFmrEF), are intriguing observations.
outcomes in the group designated as HFpEF with AF
Additional mechanistic insights are needed, which
were dismal and worse than that of HFpEF with sinus
may be provided by investigating differential atrio-
rhythm, suggesting that the former were indeed
ventricular remodeling in men versus women, and in
patients with both diagnoses. Of note, median
diabetics versus nondiabetics. Finally, the heightened
NT-proBNP levels were >2.2 times higher in AF versus
risk of death, HF hospitalization, and stroke/transient
sinus rhythm in HFpEF, compared with 1.3 times in
ischemic attack in patients with AF and HF (regardless
HFrEF and 1.1 times in HFmrEF, and NT-proBNP was
of EF) underscores the importance of recognizing
independently related to AF in HFpEF but not HFrEF
and treating AF in HF. It is notable that patients
or HFmrEF. This suggests a greater contribution of AF
with missing data on AF or EF were older and had
to NT-proBNP elevation in HFpEF compared with
worse survival than in those whose AF status was
HFrEF or HFmrEF, implying a greater potential
known. Indeed, underdetection and undertreatment
for misdiagnosis of HFpEF based on increased
of AF in HF, especially among the elderly, remains a
NT-proBNP levels in the presence of AF, and impor-
key gap to address. Closer collaboration between HF
tantly supporting the use of higher NT-proBNP
and electrophysiology specialists may be needed for
cutoffs to establish the diagnosis of HFpEF when AF
optimal strategies to better understand, detect, and
is present.
manage the common and deadly combination of AF
The paper by Sartipy et al. (2) highlights numerous
in HF.
areas for future study. The relative contribution of AF versus HF to clinical symptomatology and increased
ADDRESS FOR CORRESPONDENCE: Dr. Carolyn S.P.
NT-proBNP in an individual patient remains a clinical
Lam, National Heart Center Singapore, 5 Hospital Drive,
conundrum, particularly in HFpEF. Novel circulating
Singapore 169609. E-mail: [email protected]
REFERENCES 1. Kotecha D, Lam CSP, Van Veldhuisen DJ, Van
4. Fung JWH, Sanderson JE, Yip GWK, Zhang Q,
preserved versus reduced ejection fraction. Circu-
Gelder IC, Voors AA, Rienstra M. Heart failure with preserved ejection fraction and atrial fibrillation. J Am Coll Cardiol 2016;68:2217–28.
Yu CM. Impact of atrial fibrillation in heart failure with normal ejection fraction: a clinical and echocardiographic study. J Card Fail 2007;13: 649–55.
lation 2016;133:484–92.
2. Sartipy U, Dahlström U, Fu M, Lund LH. Atrial fibrillation in heart failure with preserved, midrange, and reduced ejection fraction. J Am Coll Cardiol HF 2017;5:XXX–XX. 3. Eapen ZJ, Greiner MA, Fonarow GC, et al. Associations between atrial fibrillation and early outcomes of patients with heart failure and reduced or preserved ejection fraction. Am Heart J 2014;167:375.e2.
5. McManus DD, Hsu G, Sung SH, et al. Atrial fibrillation and outcomes in heart failure with preserved versus reduced left ventricular ejection fraction. J Am Heart Assoc 2013;2:e005694.
7. Grigorian Shamagian L, Roman AV, Seara JG, Sande JLM, Veloso PR, Gonzalez-Juanatey JR. Atrial fibrillation in patients hospitalized for congestive heart failure: the same prognostic influence independently of left ventricular systolic function? Int J Cardiol 2006;110: 366–72.
6. Santhanakrishnan R, Wang N, Larson M, et al. Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in
KEY WORDS atrial fibrillation, heart failure, preserved ejection fraction, outcomes
3
VOL.
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
-, NO. -, 2017
ISSN 2213-1779/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jchf.2017.05.010
EDITORIAL COMMENT
Atrial Fibrillation in Heart Failure* A Common and Deadly Combination Carolyn S.P. Lam, MBBS, PHD,a,b Bernadet T. Santema, MD,b Adriaan A. Voors MD, PHDb
A
trial fibrillation (AF) and heart failure (HF)
This analysis was accomplished using the nationwide
are global cardiovascular epidemics that are
Swedish HF Registry of 41,446 patients with clinician-
inextricably linked to each other and to pop-
judged HF, linked to the National Patient Registry for
ulation aging. Prior studies have established that AF
additional data on comorbidities, HF hospitalization,
is both a risk marker and risk factor in HF, resulting
and stroke or transient ischemic attack, as well as the
from, causing, and/or adversely impacting outcomes
National Population Registry for date of death and
in HF. Most prior studies focused on HF with reduced
Statistics Sweden for socioeconomic data. The most
ejection fraction (HFrEF), where the emphasis was on
striking finding was the very high prevalence of AF:
neurohormonal activation and hemodynamic mecha-
53% in HFrEF, 60% in HFmrEF, and 65% in HFpEF
nisms perpetuating the HFrEF–AF vicious cycle. In
(Table 1). The broad inclusion of AF, defined as having
contrast, in HF with preserved EF (HFpEF), at present
a history of AF (in either the Swedish HF or National
the dominant form of HF in the United States, the
Patient Registry) or AF on electrocardiography, may
focus is on systemic inflammation and shared risk
partially explain the high prevalence. Indeed, prior
factors for both AF and HFpEF (such as aging, hyper-
studies that similarly used International Classifica-
tension, and obesity) (1). Thus, given potential differ-
tion of Diseases-Ninth Revision-Clinical Modification
ences in pathogenesis, AF may relate differently to
codes to define their AF population reported higher
HFrEF versus HFpEF; however, few studies made
prevalence of AF compared with those that used the
this comparison within the same cohort (Table 1).
electrocardiographic diagnosis (Table 1). Another
Furthermore, no prior study has examined AF in HF
explanation may be the unselected population-wide
with midrange EF (HFmrEF).
approach used in the Swedish HF cohort, which
The paper by Sartipy et al. (2) in this issue of JACC:
included patients at an advanced age. In fact, age
Heart Failure is noteworthy for being one of the
above the median of 76 years old was the strongest
largest single population-based cohorts to systemat-
risk factor for AF, more than doubling the odds of AF
ically compare AF versus sinus rhythm across the
in HF regardless of EF.
entire EF spectrum of HF, including, for the first time,
The increasing prevalence of AF with increasing
patients with HFmrEF as a distinct category (Table 1).
EF deserves further consideration. Age may be the simplest explanation for the differences between EF groups, because HFpEF patients were oldest, HFrEF
*Editorials published in JACC: Heart Failure reflect the views of the au-
youngest,
thors and do not necessarily represent the views of JACC: Heart Failure or
Figure 1 in Sartipy et al. (2) showed that at any
the American College of Cardiology.
given age the prevalence of AF was still higher in
From the aNational Heart Center Singapore, Singapore and Duke-National
HFpEF and, if anything, the difference in AF prev-
University of Singapore, Singapore; and the bDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Gronin-
and
HFmrEF
in
between.
However,
alence among HF groups widened with advancing
gen, the Netherlands. Dr. Lam has reported that she has received research
age. Beyond age, Sartipy et al. (2) also showed that
support from Boston Scientific, Bayer, Thermofisher, Medtronic, and
male sex, longer duration of HF, nonischemic eti-
Vifor Pharma; and served as a consultant for Bayer, Novartis, Takeda,
ology, and prior stroke independently increased the
Merck, Astra Zeneca, Janssen Research & Development, LLC, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Stealth BioTherapeutics,
odds of AF. The commonality of these risk factors to
Covia, Roche, and Magen. All other authors have reported that they have
HFpEF, HFmrEF, and HFrEF suggests that the HF
no relationships relevant to the contents of this paper to disclose.
syndrome per se is most strongly related to AF risk,
2
Lam et al.
JACC: HEART FAILURE VOL.
-, NO. -, 2017 - 2017:-–-
Atrial Fibrillation in Heart Failure
T A B L E 1 Real-World Cohorts With Both HFpEF and HFrEF, Comparing AF vs. Sinus Rhythm or Non-AF
Design/study
Sample Size
%HFpEF/HFmrEF/ HFrEF
LVEF cutoff %
Swedish Heart Failure Registry
41,446
23/22/55
$50 vs.
SR 74.4 12.5 AF 79.1 9.0
SR 44 AF 46
40-49 vs.
SR 70.7 13.1 AF 76.8 9.9
SR 61 AF 60
#39
SR 68.8 13.4 AF 74.3 10.7
SR 68 AF 73
$40 vs.
Non-AF 78.9 8.0 AF 80.8 7.4
Non-AF 33 AF 37
<40
Non-AF 77.6 7.6 AF 78.8 7.3
Non-AF 55 AF 61
$50 vs.
SR 71.6 8.4 AF 73.8 8.9
SR 36 AF 21
<50
SR 61.5 8.4 AF 63.0 7.1
SR 71 AF 63
Overall: Non-AF 71.6 13.1 Pre-existing AF 77.5 10.2
Overall: Non-AF 52 Pre-existing AF 52
First Author, Year (Ref. #)
Sartipy, 2017 (2)
Eapen, 2014 (3)
Retrospective, ADHERE-Core
Fung, 2007 (4)
66,357
Prospective, single center
McManus, 2013 (5)
238
Retrospective cohort
23,644
55/0/45
61/0/39
$50 vs.
60/0/40
#40 Santhanakrishnan, 2016 (6) Shamagian, 2006 (7)
Framingham Heart Study
1,166
Retrospective cohort
1,636
41/0/44 40/0/60
Age, mean SD
Sex, % Male
$45 vs.
Overall 79 11
Overall 41
<45
Overall 77 10
Overall 66
$50 vs.
Non-AF 72.7 10.6 AF 71.6 9.4
Non-AF 51 AF 46
<50
Non-AF 67.4 12.5 AF 67.5 11.3
Non-AF 69 AF 71
T A B L E 1 Continued
First Author, Year (Ref. #)
Definition AF
Sartipy, 2017 (2)
History of AF or AF on any ECG
Eapen, 2014 (3)
History of AF or ICD-9-CM code at baseline
Fung, 2007 (4)
AF on baseline ECG
McManus, 2013 (5)
ICD-9-CM code
Control (SR or Non-AF)
Clinical Correlates of AF
Outcome in AF Compared With Control (95% CI)
HFpEF 65% HFmrEF 60% HFrEF 53%
Age, male, no prior MI, duration of HF, prior stroke/TIA
HF hospitalization or death HFpEF: HR 1.17 (1.09–1.26) HFmrEF: HR 1.29 (1.20–1.40) HFrEF: HR 1.15 (1.10–1.20)
Non-AF
HFpEF 47.6% HFrEF 44.2%
Age, male, no prior MI, no DM, prior stroke/TIA
30-day mortality HFpEF: HR 1.16 (1.08–1.25) HFrEF: HR 1.00 (0.94–1.08)
SR
HFpEF 28.8% HFrEF 32.6%
Previous HF hospitalization, lower QoL
HF hospitalization or death HFpEF: HR 3.1 (1.6–5.2)
Non-AF
HFpEF 52.7% HFrEF 41.9%
Age, male, no prior MI, valvular disease
Mortality (pre-existing AF) HFpEF: HR 1.11 (1.03–1.20) HFrEF: HR 1.15 (1.05–1.26)
Santhanakrishnan, 2016 (6) Prevalent, concurrent or future AF on any ECG or hospital record
Non-AF
HFpEF 32% prevalent (18% concurrent, 12% future) HFrEF 23% prevalent (18% concurrent, 13% future)
No prior MI, no DM, preserved LVEF
Mortality (prevalent HF) New-onset AF HFpEF: HR 1.83 (1.41–2.37) HFrEF: HR 2.72 (2.12–3.48)
Shamagian, 2006 (7)
Non-AF
HFpEF 38.7% HFrEF 31.0%
No DM, nonischemic etiology, more peripheral edema, preserved LVEF
Mortality—HFpEF: no difference, Log rank 0.204 HFrEF: RR 1.83 (1.12–2.99)
AF on baseline ECG
SR
Prevalence AF
ADHERE ¼ Acute Decompensated Heart Failure National Registry; AF ¼ atrial fibrillation; DM ¼ diabetes mellitus; ECG ¼ electrocardiogram; HF ¼ heart failure; HFpEF ¼ heart failure with preserved ejection fraction; HFmrEF ¼ heart failure with mid-range ejection fraction; HFrEF ¼ heart failure with reduced ejection fraction; HR ¼ hazard ratio; ICD-9-CM ¼ International Classification of DiseasesNinth Revision-Clinical Modification; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; RR ¼ relative risk; QoL ¼ quality of life score; SR ¼ sinus rhythm; TIA ¼ transient ischemic attack.
rather than potential different mechanisms among
Another potential explanation for the highest
the HF types. The greatest prevalence of AF in
prevalence of AF in the HFpEF group is misclassifi-
HFpEF would then imply that patients with HFpEF
cation of patients with symptomatic AF, but without
had the most severe HF, and indeed these patients
true HF, as HFpEF. The inclusion criterion of patients
had the worst outcomes, even when looking only at
with clinician-judged HF in the Swedish HF Registry
patients in sinus rhythm, compared with HFrEF and
is highly relevant, because clinical judgement of HF
HFmrEF.
depends on classic symptomatology (breathlessness,
JACC: HEART FAILURE VOL.
-, NO. -, 2017
Lam et al.
- 2017:-–-
Atrial Fibrillation in Heart Failure
exertional intolerance), which overlaps with that of
biomarkers, or panels of biomarkers, may be useful
AF. Furthermore, diastolic function is challenging to
diagnostically, but require testing in cohorts of iso-
determine by echocardiography in the presence of
lated AF versus combined AF with HF (invasively
AF, and AF alone (without HF) is associated with
proven). The predisposition of men to AF in HF
increased N-terminal pro-B type natriuretic peptide
compared with women, and relative “protective”
(NT-proBNP) (1). However, one would expect better
effect of diabetes against AF in HFpEF (but not in
outcomes in patients with pure AF without HF, yet
HFrEF or HFmrEF), are intriguing observations.
outcomes in the group designated as HFpEF with AF
Additional mechanistic insights are needed, which
were dismal and worse than that of HFpEF with sinus
may be provided by investigating differential atrio-
rhythm, suggesting that the former were indeed
ventricular remodeling in men versus women, and in
patients with both diagnoses. Of note, median
diabetics versus nondiabetics. Finally, the heightened
NT-proBNP levels were >2.2 times higher in AF versus
risk of death, HF hospitalization, and stroke/transient
sinus rhythm in HFpEF, compared with 1.3 times in
ischemic attack in patients with AF and HF (regardless
HFrEF and 1.1 times in HFmrEF, and NT-proBNP was
of EF) underscores the importance of recognizing
independently related to AF in HFpEF but not HFrEF
and treating AF in HF. It is notable that patients
or HFmrEF. This suggests a greater contribution of AF
with missing data on AF or EF were older and had
to NT-proBNP elevation in HFpEF compared with
worse survival than in those whose AF status was
HFrEF or HFmrEF, implying a greater potential
known. Indeed, underdetection and undertreatment
for misdiagnosis of HFpEF based on increased
of AF in HF, especially among the elderly, remains a
NT-proBNP levels in the presence of AF, and impor-
key gap to address. Closer collaboration between HF
tantly supporting the use of higher NT-proBNP
and electrophysiology specialists may be needed for
cutoffs to establish the diagnosis of HFpEF when AF
optimal strategies to better understand, detect, and
is present.
manage the common and deadly combination of AF
The paper by Sartipy et al. (2) highlights numerous
in HF.
areas for future study. The relative contribution of AF versus HF to clinical symptomatology and increased
ADDRESS FOR CORRESPONDENCE: Dr. Carolyn S.P.
NT-proBNP in an individual patient remains a clinical
Lam, National Heart Center Singapore, 5 Hospital Drive,
conundrum, particularly in HFpEF. Novel circulating
Singapore 169609. E-mail: [email protected]
REFERENCES 1. Kotecha D, Lam CSP, Van Veldhuisen DJ, Van
4. Fung JWH, Sanderson JE, Yip GWK, Zhang Q,
preserved versus reduced ejection fraction. Circu-
Gelder IC, Voors AA, Rienstra M. Heart failure with preserved ejection fraction and atrial fibrillation. J Am Coll Cardiol 2016;68:2217–28.
Yu CM. Impact of atrial fibrillation in heart failure with normal ejection fraction: a clinical and echocardiographic study. J Card Fail 2007;13: 649–55.
lation 2016;133:484–92.
2. Sartipy U, Dahlström U, Fu M, Lund LH. Atrial fibrillation in heart failure with preserved, midrange, and reduced ejection fraction. J Am Coll Cardiol HF 2017;5:XXX–XX. 3. Eapen ZJ, Greiner MA, Fonarow GC, et al. Associations between atrial fibrillation and early outcomes of patients with heart failure and reduced or preserved ejection fraction. Am Heart J 2014;167:375.e2.
5. McManus DD, Hsu G, Sung SH, et al. Atrial fibrillation and outcomes in heart failure with preserved versus reduced left ventricular ejection fraction. J Am Heart Assoc 2013;2:e005694.
7. Grigorian Shamagian L, Roman AV, Seara JG, Sande JLM, Veloso PR, Gonzalez-Juanatey JR. Atrial fibrillation in patients hospitalized for congestive heart failure: the same prognostic influence independently of left ventricular systolic function? Int J Cardiol 2006;110: 366–72.
6. Santhanakrishnan R, Wang N, Larson M, et al. Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in
KEY WORDS atrial fibrillation, heart failure, preserved ejection fraction, outcomes
3