JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 65, NO. 3, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jacc.2014.11.009
EDITORIAL COMMENT
Stage B Heart Failure Is it More Common Than We Think?* Jae K. Oh, MD, Barry A. Borlaug, MD
T
he American College of Cardiology/American
identifying stage B (LVH) in patients with normal EF
Heart Association endorse a scheme em-
and apparent SAHF. Asymptomatic patients (N ¼ 510)
bracing the progressive nature of heart
with DM, hypertension, or obesity underwent car-
failure (HF), which exists as a continuum from
diopulmonary
asymptomatic, at-risk individuals to those with pro-
comprehensive echocardiography, including tissue
treadmill
exercise
testing
and
gressively more symptomatic disease (1). Patients
Doppler and strain imaging. The researchers defined
with HF risk factors such as diabetes mellitus (DM),
SBHF by structural remodeling (based on LVH) as in
hypertension, coronary artery disease, metabolic
the current guidelines and then added depressed
syndrome, and obesity without morphological evi-
longitudinal strain or elevated E/e 0 as additional
dence of left ventricular (LV) remodeling or low ejec-
markers. Using this scheme, SBHF was observed in
tion fraction (EF) are classified as having stage A HF
243 patients, with the remaining 267 patients defined
(SAHF). Because LV hypertrophy (LVH) and reduced
as having SAHF. Notably, about one-half (n ¼ 120) of
LVEF are associated with even greater risk of inci-
those classified with SBHF did not have significant
dent HF, asymptomatic patients with these struc-
LVH. Exercise capacity, assessed by peak oxygen
tural changes are categorized as having stage B HF
consumption (VO 2) and peak metabolic equivalents
(SBHF). HF is also linked with deterioration in car-
achieved, decreased progressively as the number of
diac systolic and diastolic function, which may
abnormal components increased in individual pa-
develop independently of structural remodeling or
tients. Although patients with SBHF, defined by
depressed EF; to date, these functional changes
elevated E/e 0 or low strain, were not as severely
have not been incorporated into the HF staging
limited as those with LVH, they were significantly
system (1).
more limited than patients with SAHF, and each inSEE PAGE 257
In this issue of the Journal, Kosmala et al. (2)
dividual functional component was independently associated with exercise capacity in multivariable analysis. The researchers concluded that novel
introduced a new concept in which novel systolic and
echocardiography-based
diastolic ventricular function parameters measured
improved the recognition of SBHF beyond what LVH
LV
functional
measures
by echocardiography can enhance SBHF identifica-
identifies alone (2). These data hold important im-
tion. They hypothesized that these sensitive mea-
plications, both for HF staging and for the design of
sures of LV function would have a similar association
future trials. Before pondering these implications
with exercise capacity as does the current standard
further, it is worth reflecting on the novel echocardiographic indexes examined in this study.
STRAIN IMAGING *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the
The most commonly used measure of systolic func-
views of JACC or the American College of Cardiology.
tion in clinical practice, LVEF, is not a robust index of
From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester,
myocardial or chamber contractility because of its
Minnesota. Dr. Oh has received consulting fees from Medtronic; and
load dependence and sensitivity to chamber size (3).
research grants from Toshiba. Dr. Borlaug has reported that he has no relationships relevant to the contents of this paper to disclose. Harvey D.
For example, when a patient has concentric remod-
White, MB, CHB, DSc, served as Guest Editor for this paper.
eling, as in LVH, HF with preserved ejection fraction
268
Oh and Borlaug
JACC VOL. 65, NO. 3, 2015 JANUARY 27, 2015:267–9
Stage B Heart Failure Is Common
(HFpEF), and hypertrophic cardiomyopathy, the
confirmed and extended on what has recently been
LV chamber volume shrinks, and thus EF tends
observed in patients with stage C HF. Individuals
to be maintained even as LV systolic function
with HFpEF have reduced systolic and diastolic tis-
diminishes (3).
sue motion, impaired cardiac output reserve, and
Strain imaging measures the extent of tissue
chronotropic incompetence (6,7,11,12). Intriguingly,
deformation as a percentage of the baseline (4,5) and
in the asymptomatic patients with SBHF studied,
can be measured in the longitudinal, circumferential,
there was also more severe chronotropic incompe-
radial, and transverse directions. Contraction along
tence as more abnormalities in LV strain, LVH, and
the longitudinal direction from the apex is the
E/e 0 were observed (2). Indeed, evidence of pro-
earliest and simplest marker of myocardial dysfunc-
gressively lower peak VO2 with increasing numbers
tion. It is reduced in almost all, if not all, forms of
of abnormalities is strikingly similar to previous data
myocardial disease, even during early asymptomatic
from our group comparing older-aged healthy vol-
stages. Tissue velocity and strain reductions occur
unteers to asymptomatic hypertensives (with SBHF)
commonly in HFpEF, and reduced longitudinal strain
with patients with HFpEF, who have progressively
has been associated with higher levels of N-terminal
more cardiovascular limitations and worse exercise
pro–B-type natriuretic peptide (BNP) (6,7). A meta-
capacity (13). In light of prior research, the findings
analysis of global longitudinal strain and LVEF
from the current study strongly support the re-
demonstrated superior prognostic value for strain
searchers’ conclusion that abnormal strain and E/e 0
compared with EF for predicting adverse outcomes in
should be added to the current scheme by which we
HFpEF, aortic stenosis, and amyloidosis (8). Accord-
define SBHF (2).
ingly, some raise the question: Should LVEF be
What might be the implications if this new defini-
replaced by global longitudinal strain (9)? One can
tion of SBHF is accepted? First, the pool of patients
make a compelling argument that strain imaging
with SBHF will grow substantially—indeed, it doubled
should be performed routinely in all patients with
in the current study beyond use of LVH alone. This
normal EF, especially when they have a risk factor
creates a larger cohort of patients in whom strategies
or are symptomatic.
can be tested to prevent HF. It is notable that Kosmala et al. observed that strain, E/e0 , and LVH were each
E/e’ (MITRAL FLOW AND ANNULUS
individually more predictive of exercise capacity than
EARLY DIASTOLIC VELOCITY RATIO)
BNP, suggesting that these novel echocardiography parameters could be used as entry criteria for future
Transmitral E measures the early diastolic velocity
trials.
of blood flowing into the LV, which is pre-load
Finally, the current data questioned whether these
dependent and increases with higher filling pres-
patients are truly “asymptomatic.” When caregivers
sure. The denominator, e0 , represents the early dia-
ask about dyspnea, patients consider it in light of
stolic velocity of mitral annular motion, which is
their daily routine, which may be limited if they are
related to the extent of LV relaxation. In patients
sedentary. The fact that striking reductions in peak
with prolonged relaxation, e 0 is relatively pre-load
VO2 were observed in patients with abnormal strain
independent. Because myocardial relaxation is im-
and E/e 0 suggests that these patients may not be as
paired in most patients with cardiac disease, as well
asymptomatic as they (or we) think they are.
as with aging, DM, and hypertension, e 0 velocity is
Appropriate use of strain and E/e 0 in clinical prac-
often reduced in these conditions. Because the E/e 0
tice requires standardization of echocardiography
numerator varies directly with pre-load and the de-
instruments and techniques. Confirmatory data from
nominator inversely with relaxation, their quotient
larger trials employing strain and diastolic function
provides a valuable noninvasive marker of filling
parameters will be important moving forward. Maybe
pressures at rest and with exercise (10). In people
the time has come to routinely apply these sensitive
with HFpEF, E/e 0 is often elevated, and Kosmala et al.
systolic and diastolic echocardiography parameters in
(2) now showed that even among people at risk for
our approach to patients with and at risk for HF.
HFpEF, an increased E/e 0 identified patients with
Kosmala et al.’s investigation urges us to do so sooner
limited exercise capacity.
rather than later.
CLINICAL IMPLICATIONS
REPRINT REQUESTS AND CORRESPONDENCE : Dr.
Jae K. Oh, Division of Cardiovascular Diseases, Mayo More than one-half of people with HF have pre-
Clinic, 200 First Street SW, Rochester, Minne-
served EF and, in SBHF, the data from Kosmala et al.
sota 55905. E-mail: [email protected].
Oh and Borlaug
JACC VOL. 65, NO. 3, 2015 JANUARY 27, 2015:267–9
Stage B Heart Failure Is Common
REFERENCES 1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147–239. 2. Kosmala W, Jellis CL, Marwick TH. Exercise limitation associated with asymptomatic left ventricular impairment: analogy with stage B heart failure. J Am Coll Cardiol 2015;65:257–66. 3. Borlaug BA, Lam CS, Roger VL, Rodeheffer RJ,
applications. Int J Cardiovasc Imaging 2009;25 Suppl 1:9–22. 6. Kraigher-Krainer E, Shah AM, Gupta DK, et al. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J Am Coll Cardiol 2014;63:447–56. 7. Tan YT, Wenzelburger F, Lee E, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion,
10. Oh JK, Kane GC. Diastolic stress echocardiography. Time has come for its integration into clinical practice. J Am Soc Echocardiogr 2014;27: 1060–3. 11. Abudiab MM, Redfield MM, Melenovsky V, et al. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur J Heart Fail 2013; 15:776–85. 12. Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 2006;114:2138–47.
Redfield MM. Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction. J Am Coll Cardiol 2009; 54:410–8.
untwist, and longitudinal motion. J Am Coll Cardiol 2009;54:36–46.
4. Marwick TH. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol 2006;47:1313–27.
strain and ejection fraction. Heart 2014;100: 1673–80.
13. Borlaug BA, Olson TP, Lam CS, et al. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 2010;56:845–54.
9. Szymanski C, Levy F, Tribouilloy. Should LVEF be replaced by global longitudinal strain? Heart 2014;100:1655–6.
KEY WORDS E/e’, heart failure staging, strain
5. Nesbitt GC, Mankad S, Oh JK. Strain imaging in echocardiography: methods and clinical
8. Kalam K, Otahal P, Marwick TH. Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal
269
VOL. 65, NO. 3, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jacc.2014.11.009
EDITORIAL COMMENT
Stage B Heart Failure Is it More Common Than We Think?* Jae K. Oh, MD, Barry A. Borlaug, MD
T
he American College of Cardiology/American
identifying stage B (LVH) in patients with normal EF
Heart Association endorse a scheme em-
and apparent SAHF. Asymptomatic patients (N ¼ 510)
bracing the progressive nature of heart
with DM, hypertension, or obesity underwent car-
failure (HF), which exists as a continuum from
diopulmonary
asymptomatic, at-risk individuals to those with pro-
comprehensive echocardiography, including tissue
treadmill
exercise
testing
and
gressively more symptomatic disease (1). Patients
Doppler and strain imaging. The researchers defined
with HF risk factors such as diabetes mellitus (DM),
SBHF by structural remodeling (based on LVH) as in
hypertension, coronary artery disease, metabolic
the current guidelines and then added depressed
syndrome, and obesity without morphological evi-
longitudinal strain or elevated E/e 0 as additional
dence of left ventricular (LV) remodeling or low ejec-
markers. Using this scheme, SBHF was observed in
tion fraction (EF) are classified as having stage A HF
243 patients, with the remaining 267 patients defined
(SAHF). Because LV hypertrophy (LVH) and reduced
as having SAHF. Notably, about one-half (n ¼ 120) of
LVEF are associated with even greater risk of inci-
those classified with SBHF did not have significant
dent HF, asymptomatic patients with these struc-
LVH. Exercise capacity, assessed by peak oxygen
tural changes are categorized as having stage B HF
consumption (VO 2) and peak metabolic equivalents
(SBHF). HF is also linked with deterioration in car-
achieved, decreased progressively as the number of
diac systolic and diastolic function, which may
abnormal components increased in individual pa-
develop independently of structural remodeling or
tients. Although patients with SBHF, defined by
depressed EF; to date, these functional changes
elevated E/e 0 or low strain, were not as severely
have not been incorporated into the HF staging
limited as those with LVH, they were significantly
system (1).
more limited than patients with SAHF, and each inSEE PAGE 257
In this issue of the Journal, Kosmala et al. (2)
dividual functional component was independently associated with exercise capacity in multivariable analysis. The researchers concluded that novel
introduced a new concept in which novel systolic and
echocardiography-based
diastolic ventricular function parameters measured
improved the recognition of SBHF beyond what LVH
LV
functional
measures
by echocardiography can enhance SBHF identifica-
identifies alone (2). These data hold important im-
tion. They hypothesized that these sensitive mea-
plications, both for HF staging and for the design of
sures of LV function would have a similar association
future trials. Before pondering these implications
with exercise capacity as does the current standard
further, it is worth reflecting on the novel echocardiographic indexes examined in this study.
STRAIN IMAGING *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the
The most commonly used measure of systolic func-
views of JACC or the American College of Cardiology.
tion in clinical practice, LVEF, is not a robust index of
From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester,
myocardial or chamber contractility because of its
Minnesota. Dr. Oh has received consulting fees from Medtronic; and
load dependence and sensitivity to chamber size (3).
research grants from Toshiba. Dr. Borlaug has reported that he has no relationships relevant to the contents of this paper to disclose. Harvey D.
For example, when a patient has concentric remod-
White, MB, CHB, DSc, served as Guest Editor for this paper.
eling, as in LVH, HF with preserved ejection fraction
268
Oh and Borlaug
JACC VOL. 65, NO. 3, 2015 JANUARY 27, 2015:267–9
Stage B Heart Failure Is Common
(HFpEF), and hypertrophic cardiomyopathy, the
confirmed and extended on what has recently been
LV chamber volume shrinks, and thus EF tends
observed in patients with stage C HF. Individuals
to be maintained even as LV systolic function
with HFpEF have reduced systolic and diastolic tis-
diminishes (3).
sue motion, impaired cardiac output reserve, and
Strain imaging measures the extent of tissue
chronotropic incompetence (6,7,11,12). Intriguingly,
deformation as a percentage of the baseline (4,5) and
in the asymptomatic patients with SBHF studied,
can be measured in the longitudinal, circumferential,
there was also more severe chronotropic incompe-
radial, and transverse directions. Contraction along
tence as more abnormalities in LV strain, LVH, and
the longitudinal direction from the apex is the
E/e 0 were observed (2). Indeed, evidence of pro-
earliest and simplest marker of myocardial dysfunc-
gressively lower peak VO2 with increasing numbers
tion. It is reduced in almost all, if not all, forms of
of abnormalities is strikingly similar to previous data
myocardial disease, even during early asymptomatic
from our group comparing older-aged healthy vol-
stages. Tissue velocity and strain reductions occur
unteers to asymptomatic hypertensives (with SBHF)
commonly in HFpEF, and reduced longitudinal strain
with patients with HFpEF, who have progressively
has been associated with higher levels of N-terminal
more cardiovascular limitations and worse exercise
pro–B-type natriuretic peptide (BNP) (6,7). A meta-
capacity (13). In light of prior research, the findings
analysis of global longitudinal strain and LVEF
from the current study strongly support the re-
demonstrated superior prognostic value for strain
searchers’ conclusion that abnormal strain and E/e 0
compared with EF for predicting adverse outcomes in
should be added to the current scheme by which we
HFpEF, aortic stenosis, and amyloidosis (8). Accord-
define SBHF (2).
ingly, some raise the question: Should LVEF be
What might be the implications if this new defini-
replaced by global longitudinal strain (9)? One can
tion of SBHF is accepted? First, the pool of patients
make a compelling argument that strain imaging
with SBHF will grow substantially—indeed, it doubled
should be performed routinely in all patients with
in the current study beyond use of LVH alone. This
normal EF, especially when they have a risk factor
creates a larger cohort of patients in whom strategies
or are symptomatic.
can be tested to prevent HF. It is notable that Kosmala et al. observed that strain, E/e0 , and LVH were each
E/e’ (MITRAL FLOW AND ANNULUS
individually more predictive of exercise capacity than
EARLY DIASTOLIC VELOCITY RATIO)
BNP, suggesting that these novel echocardiography parameters could be used as entry criteria for future
Transmitral E measures the early diastolic velocity
trials.
of blood flowing into the LV, which is pre-load
Finally, the current data questioned whether these
dependent and increases with higher filling pres-
patients are truly “asymptomatic.” When caregivers
sure. The denominator, e0 , represents the early dia-
ask about dyspnea, patients consider it in light of
stolic velocity of mitral annular motion, which is
their daily routine, which may be limited if they are
related to the extent of LV relaxation. In patients
sedentary. The fact that striking reductions in peak
with prolonged relaxation, e 0 is relatively pre-load
VO2 were observed in patients with abnormal strain
independent. Because myocardial relaxation is im-
and E/e 0 suggests that these patients may not be as
paired in most patients with cardiac disease, as well
asymptomatic as they (or we) think they are.
as with aging, DM, and hypertension, e 0 velocity is
Appropriate use of strain and E/e 0 in clinical prac-
often reduced in these conditions. Because the E/e 0
tice requires standardization of echocardiography
numerator varies directly with pre-load and the de-
instruments and techniques. Confirmatory data from
nominator inversely with relaxation, their quotient
larger trials employing strain and diastolic function
provides a valuable noninvasive marker of filling
parameters will be important moving forward. Maybe
pressures at rest and with exercise (10). In people
the time has come to routinely apply these sensitive
with HFpEF, E/e 0 is often elevated, and Kosmala et al.
systolic and diastolic echocardiography parameters in
(2) now showed that even among people at risk for
our approach to patients with and at risk for HF.
HFpEF, an increased E/e 0 identified patients with
Kosmala et al.’s investigation urges us to do so sooner
limited exercise capacity.
rather than later.
CLINICAL IMPLICATIONS
REPRINT REQUESTS AND CORRESPONDENCE : Dr.
Jae K. Oh, Division of Cardiovascular Diseases, Mayo More than one-half of people with HF have pre-
Clinic, 200 First Street SW, Rochester, Minne-
served EF and, in SBHF, the data from Kosmala et al.
sota 55905. E-mail: [email protected].
Oh and Borlaug
JACC VOL. 65, NO. 3, 2015 JANUARY 27, 2015:267–9
Stage B Heart Failure Is Common
REFERENCES 1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147–239. 2. Kosmala W, Jellis CL, Marwick TH. Exercise limitation associated with asymptomatic left ventricular impairment: analogy with stage B heart failure. J Am Coll Cardiol 2015;65:257–66. 3. Borlaug BA, Lam CS, Roger VL, Rodeheffer RJ,
applications. Int J Cardiovasc Imaging 2009;25 Suppl 1:9–22. 6. Kraigher-Krainer E, Shah AM, Gupta DK, et al. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J Am Coll Cardiol 2014;63:447–56. 7. Tan YT, Wenzelburger F, Lee E, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion,
10. Oh JK, Kane GC. Diastolic stress echocardiography. Time has come for its integration into clinical practice. J Am Soc Echocardiogr 2014;27: 1060–3. 11. Abudiab MM, Redfield MM, Melenovsky V, et al. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur J Heart Fail 2013; 15:776–85. 12. Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 2006;114:2138–47.
Redfield MM. Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction. J Am Coll Cardiol 2009; 54:410–8.
untwist, and longitudinal motion. J Am Coll Cardiol 2009;54:36–46.
4. Marwick TH. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol 2006;47:1313–27.
strain and ejection fraction. Heart 2014;100: 1673–80.
13. Borlaug BA, Olson TP, Lam CS, et al. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 2010;56:845–54.
9. Szymanski C, Levy F, Tribouilloy. Should LVEF be replaced by global longitudinal strain? Heart 2014;100:1655–6.
KEY WORDS E/e’, heart failure staging, strain
5. Nesbitt GC, Mankad S, Oh JK. Strain imaging in echocardiography: methods and clinical
8. Kalam K, Otahal P, Marwick TH. Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal
269
