- Email: [email protected]
Some Laws Were Not Made to Be Broken
JACC: CARDIOVASCULAR IMAGING
-, NO. -, 2017
VOL.
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-878X/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jcmg.2017.02.023
EDITORIAL COMMENT
Some Laws Were not Made to be Broken When Frank-Starling Reserve Is Lost in Heart Failure* Barry A. Borlaug, MD, Yogesh N.V. Reddy, MBBS
I
n 1895, Otto Frank observed that as ventricular
relevant outcomes in patients with HF. The authors
volume at end diastole increases, the systolic
prospectively examined 68 subjects with chronic HF
pressure developed within the ventricle rises
using echocardiography. While the distribution of
more rapidly. Twenty years later, Ernest Starling
heart failure with preserved ejection fraction (HFpEF)
delivered the Linacre lecture at Cambridge University
and heart failure with reduced ejection fraction
regarding his “law of the heart,” which proposed that
(HFrEF) was not presented, it appears that this cohort
the greater the stretch of the heart muscle, the greater
mostly included patients with HFrEF. RV function
its ability to perform chemical and mechanical work
was assessed by strain imaging along with traditional
in the subsequent beat (1). The fundamental impor-
measures of RV systolic function using 2-dimensional
tance of this Frank-Starling relationship in cardiovas-
imaging, M-mode, and tissue Doppler. Standard
cular physiology cannot be overstated.
measures of LV systolic and diastolic function were
In patients with heart failure (HF), the ability to
assessed along with estimates of pulmonary artery
enhance ventricular filling and ejection in response to
pressure. These comprehensive echocardiographic
stress is characteristically depressed. This is most
assessments were then repeated during lower ex-
conspicuous during the stress of physical exercise,
tremity leg positive pressure (LPP) compression to
where the heart cannot cope with heightened venous
increase venous return and augment ventricular
return from exercising muscles to meet the body’s
pre-load. Following this assessment, subjects under-
needs (2–4). Attention in HF has historically focused
went
on the left ventricle (LV) as the exclusive root cause of
testing to quantify exercise capacity (peak oxygen
this failure, but we now know that abnormalities of
uptake [VO 2]).
maximal
effort
cardiopulmonary
exercise
the right ventricular (RV) reserve are strongly asso-
In subjects with better exercise capacity (defined
ciated with impaired exercise capacity, symptom
as peak VO 2 >14 ml/kg/min), stroke volume increased
severity, and mortality in patients with HF (4–8). As
by 10% with pre-load enhancement, indicating
such, careful assessment of RV function has become
relatively
standard practice in echocardiography. However,
However, in subjects with depressed exercise capac-
resting assessment of RV function may be insensitive
ity, this reserve was absent, and stroke volume did
preserved
Frank-Starling
reserve
(10).
to important limitations in RV reserve that contribute
not change. Subjects with impaired peak VO 2 dis-
to increased morbidity and mortality in people with
played worse biventricular strain and higher filling
HF (9).
pressures estimated by E/e0 and pulmonary artery
In this issue of iJACC, Kusunose et al. (10) provide
pressures. With pre-load augmentation, both the
intriguing new data showing that assessment of RV
absolute value and change in RV strain were inde-
function during “pre-load stress” might be a new way
pendently associated with peak VO 2, with a reason-
to characterize RV reserve and relate this to clinically
ably strong correlation (r ¼ 0.7) that outperformed all of the indices of LV performance and diastolic function as predictors of aerobic capacity. The
*Editorials published in JACC: Cardiovascular Imaging reflect the views of
authors concluded that RV strain with LPP is a robust
the authors and do not necessarily represent the views of JACC:
predictor of exercise capacity in HF patients that
Cardiovascular Imaging or the American College of Cardiology.
could be used to identify individuals with more
From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester,
severely reduced exercise capacity (10).
Minnesota. Dr. Borlaug is supported by National Heart, Lung, and Blood Institute (NHLBI) grant numbers RO1 HL128526 and U10
The authors are to be commended on this impor-
HL110262. Dr. Reddy is supported by National Heart, Lung, and Blood
tant work using a simple but elegant provocative
Institute (NHLBI) grant number T32 HL007111.
maneuver that could someday be applied in the
2
Borlaug and Reddy
JACC: CARDIOVASCULAR IMAGING, VOL.
-, NO. -, 2017 - 2017:-–-
Editorial Comment
echocardiography laboratory to better understand
patients with severe tricuspid regurgitation who
cardiac reserve in people with numerous cardiovas-
often develop increase in LV filling pressures owing
cular diseases (10). Many patients with HF, especially
to right heart overload, even when there is not
HFpEF, appear to have relatively preserved cardiac
severe left heart disease present (14). Increased VI
function at rest, only to develop marked limitations
also affects patients with HFpEF, especially in the
in ventricular reserve during exercise (3,4). Recent
setting of obesity, where VI contributes even more
studies have identified a potential role for exercise
to elevation in cardiac filling pressures during
echocardiography to help characterize these patients,
exercise (15). In fact, a recent study has shown that
but it is not possible to obtain diagnostic quality
targeting VI with anterior pericardial resection can
echocardiographic imaging during exercise in a sub-
mitigate the increase in LV filling pressures with
stantial number of patients, even in highly controlled
volume loading, suggesting that this could be a
research settings (11). As such, the identification of
novel potential treatment for HFpEF (16).
alternative ways to “stress the heart,” in this case
Putting the new data from Kusunose et al. (10)
through LPP (enhanced pre-load), is an attractive
together with these earlier studies, we can conclude
option that merits further testing.
that HF patients with severe exercise intolerance
The strong association observed between biven-
and RV dysfunction are likely to be the ones with
tricular function and exercise capacity in this pre-
the largest amounts of VI, and that this greatly
dominantly HFrEF population (10) confirms and
limits recruitment of Frank-Starling reserve (12,14).
extends upon a recent study performed in subjects
This observation has potentially important thera-
with HFpEF, providing greater pathophysiological
peutic implications. In a landmark paper, Atherton
insight (4). However, it is worth pointing out that the
et al. (13) showed in HFrEF patients that acute
authors did not perform analysis to determine
unloading of the RV with lower body suction
whether assessment of RV strain during LPP was
improved forward stroke volume because the LV
superior to assessments performed at rest (10), and
filling was enhanced as VI and pericardial restraint
this is certainly an important and as-yet unanswered
were released. In essence, the opposite experiment
question. The authors discuss how failure to enhance
was performed here. As shown in Figure 2 of
RV strain may indicate poor RV reserve, but they do
Kusunose et al. (10), a number of the patients dis-
not account for what was likely an important
played a reduction in stroke volume with LPP, and
contributor to explaining their observed correlations
presumably, this would be the cohort most likely to
with
benefit from reduction in RV overload, perhaps
exercise
disability—the
phenomenon
of
using more aggressive vasodilators or diuretics (13).
enhanced ventricular interaction (VI) (12). Dilatation and dysfunction of the RV may raise
Other
potential
indications
for
pre-load-stress
LV end-diastolic pressure even when LV end-
echocardiography approach might be the evalua-
diastolic volume remains unchanged or decreases.
tion of HFpEF in patients with exertional dyspnea
This is because the anatomical arrangement of
(11,17), or characterization of RV reserve while
the LV and RV causes the septum to shift from right
contemplating higher risk surgical therapies for HF,
to left as RV overload progresses, such that the RV
such as tricuspid valve replacement or ventricular
“outcompetes” the LV for the limited space avail-
assist device implantation (18). These questions
able in the pericardial sac (12–14). This relationship,
merit future study.
termed diastolic VI, is enhanced in many patients
A century has passed since Starling popularized his
with HF. The absent increase in stroke volume (SV)
“law of the heart,” but clinicians and physiologists
with LPP noted by the authors in patients with
alike are still thinking about it today (1). The study
poor exercise capacity in the current study (10)
from Kusunose et al. (10) reminds us why it is
likely
as
important to adhere to these laws in health, and what
described by Janicki (12) nearly 30 years ago, where
we can do to help understand and treat our patients
HFrEF patients with severe exercise intolerance
in whom this law has been broken.
reflects
the
same
pathophysiology
(peak VO 2 <10 ml/kg/min) displayed a flat stroke volume response to exercise that was coupled with
ADDRESS
equal increases in LV and RV diastolic filling pres-
Borlaug, Division of Cardiovascular Diseases, Mayo
sures
Clinic and Foundation, 200 First Street SW, Rochester,
caused
by
increased
VI
and
pericardial
restraint (12). The same phenomenon is present in
FOR
CORRESPONDENCE:
Dr. Barry A.
Minnesota 55905. E-mail: [email protected].
JACC: CARDIOVASCULAR IMAGING, VOL.
-, NO. -, 2017
Borlaug and Reddy
- 2017:-–-
Editorial Comment
REFERENCES 1. Katz AM. Ernest Henry Starling, his predecessors, and the “Law of the Heart.” Circulation 2002;106:2986–92. 2. Sullivan MJ, Knight JD, Higginbotham MB, Cobb FR. Relation between central and peripheral
7. Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J 2014;35:3452–62. 8. Mohammed
SF,
Hussain
I,
Abou
hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 1989;80:769–81.
Ezzeddine OF, et al. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 2014; 130:2310–20.
3. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail 2010;3:
9. Guazzi M, Villani S, Generati G, et al. Right ventricular contractile reserve and pulmonary circulation uncoupling during exercise challenge in heart failure: pathophysiology and clinical phe-
588–95.
notypes. J Am Coll Cardiol HF 2016;4:625–35.
4. Borlaug BA, Kane GC, Melenovsky V, Olson TP.
10. Kusunose K, Yamada H, Nishio S, et al. RV
Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. Eur Heart J 2016;37:3293–302.
myocardial strain during pre-load augmentation is associated with exercise capacity in patients with chronic HF. J Am Coll Cardiol Img 2017;10: XX–XX.
5. Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol 1995; 25:1143–53.
11. Obokata M, Kane GC, Reddy YN, Olson TP, Melenovsky V, Borlaug BA. The role of diastolic stress testing in the evaluation for heart failure with preserved ejection fraction: a simultaneous
6. Ghio S, Gavazzi A, Campana C, et al. Independent and additive prognostic value of
invasive-echocardiographic 2017;135:825–38.
study.
Circulation
right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001;37: 183–8.
12. Janicki JS. Influence of the pericardium and ventricular interdependence on left ventricular diastolic and systolic function in patients with heart failure. Circulation 1990;81:III15–20.
13. Atherton JJ, Moore TD, Lele SS, et al. Diastolic ventricular interaction in chronic heart failure. Lancet 1997;349:1720–4. 14. Andersen MJ, Nishimura RA, Borlaug BA. The hemodynamic basis of exercise intolerance in tricuspid regurgitation. Circ Heart Fail 2014;7:911–7. 15. Obokata
M,
Reddy
YN,
Pislaru
SV,
Melenovsky V, Borlaug BA. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 2017 Apr 5 [E-pub ahead of print]. 16. Borlaug BA, Carter RE, Melenovsky V, et al. Percutaneous pericardial resection: a novel potential treatment for heart failure with preserved ejection fraction. Circ Heart Fail 2017;10:e003612. 17. Andersen MJ, Olson TP, Melenovsky V, Kane GC, Borlaug BA. Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail 2015;8:41–8. 18. Grant AD, Smedira NG, Starling RC, Marwick TH. Independent and incremental role of quantitative right ventricular evaluation for the prediction of right ventricular failure after left ventricular assist device implantation. J Am Coll Cardiol 2012;60:521–8.
KEY WORDS exercise capacity, pre-load augmentation, strain imaging
3
-, NO. -, 2017
VOL.
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-878X/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jcmg.2017.02.023
EDITORIAL COMMENT
Some Laws Were not Made to be Broken When Frank-Starling Reserve Is Lost in Heart Failure* Barry A. Borlaug, MD, Yogesh N.V. Reddy, MBBS
I
n 1895, Otto Frank observed that as ventricular
relevant outcomes in patients with HF. The authors
volume at end diastole increases, the systolic
prospectively examined 68 subjects with chronic HF
pressure developed within the ventricle rises
using echocardiography. While the distribution of
more rapidly. Twenty years later, Ernest Starling
heart failure with preserved ejection fraction (HFpEF)
delivered the Linacre lecture at Cambridge University
and heart failure with reduced ejection fraction
regarding his “law of the heart,” which proposed that
(HFrEF) was not presented, it appears that this cohort
the greater the stretch of the heart muscle, the greater
mostly included patients with HFrEF. RV function
its ability to perform chemical and mechanical work
was assessed by strain imaging along with traditional
in the subsequent beat (1). The fundamental impor-
measures of RV systolic function using 2-dimensional
tance of this Frank-Starling relationship in cardiovas-
imaging, M-mode, and tissue Doppler. Standard
cular physiology cannot be overstated.
measures of LV systolic and diastolic function were
In patients with heart failure (HF), the ability to
assessed along with estimates of pulmonary artery
enhance ventricular filling and ejection in response to
pressure. These comprehensive echocardiographic
stress is characteristically depressed. This is most
assessments were then repeated during lower ex-
conspicuous during the stress of physical exercise,
tremity leg positive pressure (LPP) compression to
where the heart cannot cope with heightened venous
increase venous return and augment ventricular
return from exercising muscles to meet the body’s
pre-load. Following this assessment, subjects under-
needs (2–4). Attention in HF has historically focused
went
on the left ventricle (LV) as the exclusive root cause of
testing to quantify exercise capacity (peak oxygen
this failure, but we now know that abnormalities of
uptake [VO 2]).
maximal
effort
cardiopulmonary
exercise
the right ventricular (RV) reserve are strongly asso-
In subjects with better exercise capacity (defined
ciated with impaired exercise capacity, symptom
as peak VO 2 >14 ml/kg/min), stroke volume increased
severity, and mortality in patients with HF (4–8). As
by 10% with pre-load enhancement, indicating
such, careful assessment of RV function has become
relatively
standard practice in echocardiography. However,
However, in subjects with depressed exercise capac-
resting assessment of RV function may be insensitive
ity, this reserve was absent, and stroke volume did
preserved
Frank-Starling
reserve
(10).
to important limitations in RV reserve that contribute
not change. Subjects with impaired peak VO 2 dis-
to increased morbidity and mortality in people with
played worse biventricular strain and higher filling
HF (9).
pressures estimated by E/e0 and pulmonary artery
In this issue of iJACC, Kusunose et al. (10) provide
pressures. With pre-load augmentation, both the
intriguing new data showing that assessment of RV
absolute value and change in RV strain were inde-
function during “pre-load stress” might be a new way
pendently associated with peak VO 2, with a reason-
to characterize RV reserve and relate this to clinically
ably strong correlation (r ¼ 0.7) that outperformed all of the indices of LV performance and diastolic function as predictors of aerobic capacity. The
*Editorials published in JACC: Cardiovascular Imaging reflect the views of
authors concluded that RV strain with LPP is a robust
the authors and do not necessarily represent the views of JACC:
predictor of exercise capacity in HF patients that
Cardiovascular Imaging or the American College of Cardiology.
could be used to identify individuals with more
From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester,
severely reduced exercise capacity (10).
Minnesota. Dr. Borlaug is supported by National Heart, Lung, and Blood Institute (NHLBI) grant numbers RO1 HL128526 and U10
The authors are to be commended on this impor-
HL110262. Dr. Reddy is supported by National Heart, Lung, and Blood
tant work using a simple but elegant provocative
Institute (NHLBI) grant number T32 HL007111.
maneuver that could someday be applied in the
2
Borlaug and Reddy
JACC: CARDIOVASCULAR IMAGING, VOL.
-, NO. -, 2017 - 2017:-–-
Editorial Comment
echocardiography laboratory to better understand
patients with severe tricuspid regurgitation who
cardiac reserve in people with numerous cardiovas-
often develop increase in LV filling pressures owing
cular diseases (10). Many patients with HF, especially
to right heart overload, even when there is not
HFpEF, appear to have relatively preserved cardiac
severe left heart disease present (14). Increased VI
function at rest, only to develop marked limitations
also affects patients with HFpEF, especially in the
in ventricular reserve during exercise (3,4). Recent
setting of obesity, where VI contributes even more
studies have identified a potential role for exercise
to elevation in cardiac filling pressures during
echocardiography to help characterize these patients,
exercise (15). In fact, a recent study has shown that
but it is not possible to obtain diagnostic quality
targeting VI with anterior pericardial resection can
echocardiographic imaging during exercise in a sub-
mitigate the increase in LV filling pressures with
stantial number of patients, even in highly controlled
volume loading, suggesting that this could be a
research settings (11). As such, the identification of
novel potential treatment for HFpEF (16).
alternative ways to “stress the heart,” in this case
Putting the new data from Kusunose et al. (10)
through LPP (enhanced pre-load), is an attractive
together with these earlier studies, we can conclude
option that merits further testing.
that HF patients with severe exercise intolerance
The strong association observed between biven-
and RV dysfunction are likely to be the ones with
tricular function and exercise capacity in this pre-
the largest amounts of VI, and that this greatly
dominantly HFrEF population (10) confirms and
limits recruitment of Frank-Starling reserve (12,14).
extends upon a recent study performed in subjects
This observation has potentially important thera-
with HFpEF, providing greater pathophysiological
peutic implications. In a landmark paper, Atherton
insight (4). However, it is worth pointing out that the
et al. (13) showed in HFrEF patients that acute
authors did not perform analysis to determine
unloading of the RV with lower body suction
whether assessment of RV strain during LPP was
improved forward stroke volume because the LV
superior to assessments performed at rest (10), and
filling was enhanced as VI and pericardial restraint
this is certainly an important and as-yet unanswered
were released. In essence, the opposite experiment
question. The authors discuss how failure to enhance
was performed here. As shown in Figure 2 of
RV strain may indicate poor RV reserve, but they do
Kusunose et al. (10), a number of the patients dis-
not account for what was likely an important
played a reduction in stroke volume with LPP, and
contributor to explaining their observed correlations
presumably, this would be the cohort most likely to
with
benefit from reduction in RV overload, perhaps
exercise
disability—the
phenomenon
of
using more aggressive vasodilators or diuretics (13).
enhanced ventricular interaction (VI) (12). Dilatation and dysfunction of the RV may raise
Other
potential
indications
for
pre-load-stress
LV end-diastolic pressure even when LV end-
echocardiography approach might be the evalua-
diastolic volume remains unchanged or decreases.
tion of HFpEF in patients with exertional dyspnea
This is because the anatomical arrangement of
(11,17), or characterization of RV reserve while
the LV and RV causes the septum to shift from right
contemplating higher risk surgical therapies for HF,
to left as RV overload progresses, such that the RV
such as tricuspid valve replacement or ventricular
“outcompetes” the LV for the limited space avail-
assist device implantation (18). These questions
able in the pericardial sac (12–14). This relationship,
merit future study.
termed diastolic VI, is enhanced in many patients
A century has passed since Starling popularized his
with HF. The absent increase in stroke volume (SV)
“law of the heart,” but clinicians and physiologists
with LPP noted by the authors in patients with
alike are still thinking about it today (1). The study
poor exercise capacity in the current study (10)
from Kusunose et al. (10) reminds us why it is
likely
as
important to adhere to these laws in health, and what
described by Janicki (12) nearly 30 years ago, where
we can do to help understand and treat our patients
HFrEF patients with severe exercise intolerance
in whom this law has been broken.
reflects
the
same
pathophysiology
(peak VO 2 <10 ml/kg/min) displayed a flat stroke volume response to exercise that was coupled with
ADDRESS
equal increases in LV and RV diastolic filling pres-
Borlaug, Division of Cardiovascular Diseases, Mayo
sures
Clinic and Foundation, 200 First Street SW, Rochester,
caused
by
increased
VI
and
pericardial
restraint (12). The same phenomenon is present in
FOR
CORRESPONDENCE:
Dr. Barry A.
Minnesota 55905. E-mail: [email protected].
JACC: CARDIOVASCULAR IMAGING, VOL.
-, NO. -, 2017
Borlaug and Reddy
- 2017:-–-
Editorial Comment
REFERENCES 1. Katz AM. Ernest Henry Starling, his predecessors, and the “Law of the Heart.” Circulation 2002;106:2986–92. 2. Sullivan MJ, Knight JD, Higginbotham MB, Cobb FR. Relation between central and peripheral
7. Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J 2014;35:3452–62. 8. Mohammed
SF,
Hussain
I,
Abou
hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 1989;80:769–81.
Ezzeddine OF, et al. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 2014; 130:2310–20.
3. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail 2010;3:
9. Guazzi M, Villani S, Generati G, et al. Right ventricular contractile reserve and pulmonary circulation uncoupling during exercise challenge in heart failure: pathophysiology and clinical phe-
588–95.
notypes. J Am Coll Cardiol HF 2016;4:625–35.
4. Borlaug BA, Kane GC, Melenovsky V, Olson TP.
10. Kusunose K, Yamada H, Nishio S, et al. RV
Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. Eur Heart J 2016;37:3293–302.
myocardial strain during pre-load augmentation is associated with exercise capacity in patients with chronic HF. J Am Coll Cardiol Img 2017;10: XX–XX.
5. Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol 1995; 25:1143–53.
11. Obokata M, Kane GC, Reddy YN, Olson TP, Melenovsky V, Borlaug BA. The role of diastolic stress testing in the evaluation for heart failure with preserved ejection fraction: a simultaneous
6. Ghio S, Gavazzi A, Campana C, et al. Independent and additive prognostic value of
invasive-echocardiographic 2017;135:825–38.
study.
Circulation
right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001;37: 183–8.
12. Janicki JS. Influence of the pericardium and ventricular interdependence on left ventricular diastolic and systolic function in patients with heart failure. Circulation 1990;81:III15–20.
13. Atherton JJ, Moore TD, Lele SS, et al. Diastolic ventricular interaction in chronic heart failure. Lancet 1997;349:1720–4. 14. Andersen MJ, Nishimura RA, Borlaug BA. The hemodynamic basis of exercise intolerance in tricuspid regurgitation. Circ Heart Fail 2014;7:911–7. 15. Obokata
M,
Reddy
YN,
Pislaru
SV,
Melenovsky V, Borlaug BA. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 2017 Apr 5 [E-pub ahead of print]. 16. Borlaug BA, Carter RE, Melenovsky V, et al. Percutaneous pericardial resection: a novel potential treatment for heart failure with preserved ejection fraction. Circ Heart Fail 2017;10:e003612. 17. Andersen MJ, Olson TP, Melenovsky V, Kane GC, Borlaug BA. Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail 2015;8:41–8. 18. Grant AD, Smedira NG, Starling RC, Marwick TH. Independent and incremental role of quantitative right ventricular evaluation for the prediction of right ventricular failure after left ventricular assist device implantation. J Am Coll Cardiol 2012;60:521–8.
KEY WORDS exercise capacity, pre-load augmentation, strain imaging
3