JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 64, NO. 12, 2014
ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jacc.2014.07.021
EDITORIAL COMMENT
Between a Rock and a Hard Place* Mario Jorge Garcia, MD
T
he most common valvular lesion seen in the
The detection of severe leaflet calcification, in
U.S. adult population, aortic stenosis (AS)
addition to increased aortic velocity, by echocardio-
exhibits an estimated prevalence of 20% in
graphy has been associated with adverse outcomes
those >80 years of age (1). Degenerative aortic valve
(5), but leaflet calcification is hard to quantify due to
calcification (AVC) is the most common cause of AS,
the variable attenuation that dense calcification pro-
accounting for 82% of cases (2). In clinical practice,
duces on the ultrasound beam. Attenuation is quan-
the diagnosis of AS and the estimation of AS severity
tifiable and reproducible on x-ray, unlike ultrasound,
rely primarily on echocardiography. Whereas 2-
and x-ray has been extensively validated for the
and 3-dimensional echocardiography allow for the
assessment of coronary artery calcification using
anatomical evaluation of leaflet morphology and
electrocardiography-gated
left ventricular
size, mass, and function,
(CT). The reproducibility of measurements of AVC by
Doppler echocardiography provides physiological
CT has been previously demonstrated, as have its
assessment of AS severity and has largely eliminated
correlations with histology and the hemodynamic
the need for invasive hemodynamic studies (3).
severity of AS (9). Severe AVC by CT has also been
The prognostic significance of high aortic Doppler
associated with more rapid stenosis progression (10)
velocities/high gradients has been reported in large
and increased short-term adverse clinical outcomes
series of patients with longitudinal follow-up (4–6)
in patients with asymptomatic AS (11).
and
has
been
(LV)
incorporated
into
the
computed
tomography
American
College of Cardiology/American Heart Association
SEE PAGE 1202
guidelines (7). Nonetheless, although a velocity >4.0 m/s is highly
In this issue of the Journal, Clavel et al. (12)
specific for severe AS, it lacks sensitivity (4) because
examine the role of AVC as an independent predic-
transvalvular velocities/gradients are flow dependent
tor of mortality in a large cohort of patients with AS.
and may be reduced in patients with severe AS and
In their study, both AVC and AVC density indepen-
low cardiac output. Estimation of the aortic valve area
dently predicted mortality with medical management
may also be inaccurate due to variations in the
after adjustment for age, sex, symptoms, coronary
anatomical shape of the outflow tract, misplacement
artery disease, diabetes, LV ejection fraction, and
of the Doppler sample volume, and/or misalignment
echocardiographic indices of hemodynamic severity.
with flow direction. Moreover, the effective orifice
The addition of AVC increased the correct classifica-
area calculated by continuity is also flow dependent
tion of high versus low risk by 12.5%. Moreover,
(8), leading to potential underestimation of valve area
among patients with severe AVC, surgery conveyed a
in patients with low flow.
survival advantage over medical therapy. These novel results demonstrate the additional prognostic value of CT over the echocardiographic indices accepted by established guidelines. Given the high reproduc-
*Editorials published in the Journal of the American College of Cardiology
ibility, relatively low cost, and potentially important
reflect the views of the authors and do not necessarily represent the
additional
views of JACC or the American College of Cardiology. From the Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Dr. Garcia has received
information
obtained
by
noncontrast
electrocardiography-gated CT, such as coronary calcium score and extent of aortic root calcification, this
royalties from Elsevier Inc. and Wolters Kluwer; and owns stock options
test would seem to provide high benefit–cost and
in Pfizer Inc.
benefit–risk ratios.
JACC VOL. 64, NO. 12, 2014
Garcia
SEPTEMBER 23, 2014:1214–6
Between a Rock and a Hard Place
Further studies will be needed, however, before we
aortic valve stenosis has been reported to be 19% to
can determine when and how we should rely on CT
29% in patients undergoing preoperative invasive
for clinical decision making. The patient cohort in the
hemodynamic evaluation, and severe pulmonary
study by Clavel et al. (12) represents a selected group
hypertension is also associated with increased peri-
that underwent both echocardiography and CT.
operative mortality (17). The inclusion of these
Whereas clinical guidelines clearly define the in-
additional indices, which are routinely obtained
dications for performing echocardiographic studies,
on transthoracic echocardiography, could limit the
the criteria that may have been used for performing
added prognostic utility of AVC.
CT are unclear, thereby potentially introducing a se-
Finally, whereas the present study demonstrates
lection bias that may limit the wider applicability of
that in this selected cohort, aortic valve implantation
the study results.
conveyed a survival advantage over medical therapy,
Whereas the roles of inflammation and oxidative
primarily in those patients with increased AVC, one
stress in the genesis of AS have been largely
may not conclude that increased AVC alone should
established (13), we also find calcific AS in numerous
constitute an indication for surgery. Because there
conditions with increased calcium turnover, such as
was no randomization to therapy, it is plausible that
Paget disease and end-stage renal disease. Renal
many of the patients with increased AVC who did not
disease has been recognized as an important deter-
undergo surgery had a greater number of comorbid-
minant of outcomes in patients with AS undergoing
ities and/or a shorter life expectancy and were
valve implantation (14) and, more recently, trans-
considered high surgical risk. Thus, knowledge of
catheter aortic valve implantation (15). It is unclear
AVC may not have altered clinical decision making or
whether high AVC may be a manifestation of impaired
have changed the observed outcomes.
renal function in many of these patients and would remain
an
independent
prognostic
factor
after
adjustment for serum creatinine.
Meanwhile, until we have the answers to all of these questions, many of us determining how to treat the truly high-risk AS patient will remain stuck
Patients with AS develop concentric LV hyper-
between a rock and a hard place.
trophy as an adaptive mechanism to normalize wall stress of the pressure-overloaded ventricle. In these
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
patients, the severity of diastolic dysfunction has an
Mario
important impact on long-term mortality after aortic
Montefiore Medical Center, Albert Einstein College
valve implantation (16). The prevalence of severe
of Medicine, 111 East 210th Street, Bronx, New
pulmonary hypertension in patients with severe
York 10467. E-mail: mariogar@montefiore.org.
Jorge
Garcia,
Department
of
Cardiology,
REFERENCES 1. Aronow WS, Kronzon I. Prevalence and severity of valvular aortic stenosis determined by Doppler echocardiography and its association with echocardiographic and electrocardiographic left ventricular hypertrophy and physical signs of aortic stenosis in elderly patients. Am J Cardiol 1991;67:
5. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95: 2262–70.
776–7.
6. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005;111:
2. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease. Euro Heart J 2003;24: 1231–43. 3. Feuchtner GM, Dichtl W, Friedrich GJ, et al. Multislice computed tomography for detection of patients with aortic valve stenosis and quantification of severity. J Am Coll Cardiol 2006;47: 1410–7.
3290–5. 7. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63: 2438–88.
4. Oh JK, Taliercio CP, Holmes DR Jr., et al. Prediction of the severity of aortic stenosis
8. Burwash IG, Thomas DD, Sadahiro M, et al.
by Doppler aortic valve area determination: prospective Doppler-catheterization correlation in 100 patients. J Am Coll Cardiol 1988;11: 1227–34.
Dependence of Gorlin formula and continuity equation valve areas on transvalvular volume flow rate in valvular aortic stenosis. Circulation 1994; 89:827–35.
9. Messika-Zeitoun D, Aubry MC, Detaint D, et al. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation 2004;110: 356–62. 10. Pohle K, Maffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001;104:1927–32. 11. Feuchtner GM, Muller S, Grander W, et al. Aortic valve calcification as quantified with multislice computed tomography predicts shortterm clinical outcome in patients with asymptomatic aortic stenosis. J Heart Valve Dis 2006;15: 494–8. 12. Clavel M-A, Pirabot P, Messika-Zeitoun D, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol 2014;64:1202–13. 13. Miller JD, Chu Y, Brooks RM, Richenbacher WE, Pena-Silva R, Heistad DD. Dysregulation of antioxidant mechanisms contributes to increased
1215
1216
Garcia
JACC VOL. 64, NO. 12, 2014
Between a Rock and a Hard Place
SEPTEMBER 23, 2014:1214–6
oxidative stress in calcific aortic valvular stenosis in humans. J Am Coll Cardiol 2008;52: 843–50. 14. Brown JM, O’Brien SM, Wu C, Sikora JA, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg 2009;137:82–90.
15. Yamamoto M, Hayashida K, Mouillet G, et al. Prognostic value of chronic kidney disease after transcatheter aortic valve implantation. J Am Coll Cardiol 2013;62:869–77.
17. Malouf JF, Enriquez-Sarano M, Pellikka PA, et al. Severe pulmonary hypertension in patients with severe aortic valve stenosis: clinical profile and prognostic implications. J Am Coll Cardiol
16. Gjertsson P, Caidahl K, Farasati M, Oden A, Bech-Hanssen O. Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients
2002;40:789–95.
with severe aortic stenosis. J Thorac Cardiovasc Surg 2005;129:890–6.
KEY WORDS aortic stenosis, computed tomography, echocardiography
VOL. 64, NO. 12, 2014
ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jacc.2014.07.021
EDITORIAL COMMENT
Between a Rock and a Hard Place* Mario Jorge Garcia, MD
T
he most common valvular lesion seen in the
The detection of severe leaflet calcification, in
U.S. adult population, aortic stenosis (AS)
addition to increased aortic velocity, by echocardio-
exhibits an estimated prevalence of 20% in
graphy has been associated with adverse outcomes
those >80 years of age (1). Degenerative aortic valve
(5), but leaflet calcification is hard to quantify due to
calcification (AVC) is the most common cause of AS,
the variable attenuation that dense calcification pro-
accounting for 82% of cases (2). In clinical practice,
duces on the ultrasound beam. Attenuation is quan-
the diagnosis of AS and the estimation of AS severity
tifiable and reproducible on x-ray, unlike ultrasound,
rely primarily on echocardiography. Whereas 2-
and x-ray has been extensively validated for the
and 3-dimensional echocardiography allow for the
assessment of coronary artery calcification using
anatomical evaluation of leaflet morphology and
electrocardiography-gated
left ventricular
size, mass, and function,
(CT). The reproducibility of measurements of AVC by
Doppler echocardiography provides physiological
CT has been previously demonstrated, as have its
assessment of AS severity and has largely eliminated
correlations with histology and the hemodynamic
the need for invasive hemodynamic studies (3).
severity of AS (9). Severe AVC by CT has also been
The prognostic significance of high aortic Doppler
associated with more rapid stenosis progression (10)
velocities/high gradients has been reported in large
and increased short-term adverse clinical outcomes
series of patients with longitudinal follow-up (4–6)
in patients with asymptomatic AS (11).
and
has
been
(LV)
incorporated
into
the
computed
tomography
American
College of Cardiology/American Heart Association
SEE PAGE 1202
guidelines (7). Nonetheless, although a velocity >4.0 m/s is highly
In this issue of the Journal, Clavel et al. (12)
specific for severe AS, it lacks sensitivity (4) because
examine the role of AVC as an independent predic-
transvalvular velocities/gradients are flow dependent
tor of mortality in a large cohort of patients with AS.
and may be reduced in patients with severe AS and
In their study, both AVC and AVC density indepen-
low cardiac output. Estimation of the aortic valve area
dently predicted mortality with medical management
may also be inaccurate due to variations in the
after adjustment for age, sex, symptoms, coronary
anatomical shape of the outflow tract, misplacement
artery disease, diabetes, LV ejection fraction, and
of the Doppler sample volume, and/or misalignment
echocardiographic indices of hemodynamic severity.
with flow direction. Moreover, the effective orifice
The addition of AVC increased the correct classifica-
area calculated by continuity is also flow dependent
tion of high versus low risk by 12.5%. Moreover,
(8), leading to potential underestimation of valve area
among patients with severe AVC, surgery conveyed a
in patients with low flow.
survival advantage over medical therapy. These novel results demonstrate the additional prognostic value of CT over the echocardiographic indices accepted by established guidelines. Given the high reproduc-
*Editorials published in the Journal of the American College of Cardiology
ibility, relatively low cost, and potentially important
reflect the views of the authors and do not necessarily represent the
additional
views of JACC or the American College of Cardiology. From the Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Dr. Garcia has received
information
obtained
by
noncontrast
electrocardiography-gated CT, such as coronary calcium score and extent of aortic root calcification, this
royalties from Elsevier Inc. and Wolters Kluwer; and owns stock options
test would seem to provide high benefit–cost and
in Pfizer Inc.
benefit–risk ratios.
JACC VOL. 64, NO. 12, 2014
Garcia
SEPTEMBER 23, 2014:1214–6
Between a Rock and a Hard Place
Further studies will be needed, however, before we
aortic valve stenosis has been reported to be 19% to
can determine when and how we should rely on CT
29% in patients undergoing preoperative invasive
for clinical decision making. The patient cohort in the
hemodynamic evaluation, and severe pulmonary
study by Clavel et al. (12) represents a selected group
hypertension is also associated with increased peri-
that underwent both echocardiography and CT.
operative mortality (17). The inclusion of these
Whereas clinical guidelines clearly define the in-
additional indices, which are routinely obtained
dications for performing echocardiographic studies,
on transthoracic echocardiography, could limit the
the criteria that may have been used for performing
added prognostic utility of AVC.
CT are unclear, thereby potentially introducing a se-
Finally, whereas the present study demonstrates
lection bias that may limit the wider applicability of
that in this selected cohort, aortic valve implantation
the study results.
conveyed a survival advantage over medical therapy,
Whereas the roles of inflammation and oxidative
primarily in those patients with increased AVC, one
stress in the genesis of AS have been largely
may not conclude that increased AVC alone should
established (13), we also find calcific AS in numerous
constitute an indication for surgery. Because there
conditions with increased calcium turnover, such as
was no randomization to therapy, it is plausible that
Paget disease and end-stage renal disease. Renal
many of the patients with increased AVC who did not
disease has been recognized as an important deter-
undergo surgery had a greater number of comorbid-
minant of outcomes in patients with AS undergoing
ities and/or a shorter life expectancy and were
valve implantation (14) and, more recently, trans-
considered high surgical risk. Thus, knowledge of
catheter aortic valve implantation (15). It is unclear
AVC may not have altered clinical decision making or
whether high AVC may be a manifestation of impaired
have changed the observed outcomes.
renal function in many of these patients and would remain
an
independent
prognostic
factor
after
adjustment for serum creatinine.
Meanwhile, until we have the answers to all of these questions, many of us determining how to treat the truly high-risk AS patient will remain stuck
Patients with AS develop concentric LV hyper-
between a rock and a hard place.
trophy as an adaptive mechanism to normalize wall stress of the pressure-overloaded ventricle. In these
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
patients, the severity of diastolic dysfunction has an
Mario
important impact on long-term mortality after aortic
Montefiore Medical Center, Albert Einstein College
valve implantation (16). The prevalence of severe
of Medicine, 111 East 210th Street, Bronx, New
pulmonary hypertension in patients with severe
York 10467. E-mail: mariogar@montefiore.org.
Jorge
Garcia,
Department
of
Cardiology,
REFERENCES 1. Aronow WS, Kronzon I. Prevalence and severity of valvular aortic stenosis determined by Doppler echocardiography and its association with echocardiographic and electrocardiographic left ventricular hypertrophy and physical signs of aortic stenosis in elderly patients. Am J Cardiol 1991;67:
5. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95: 2262–70.
776–7.
6. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005;111:
2. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease. Euro Heart J 2003;24: 1231–43. 3. Feuchtner GM, Dichtl W, Friedrich GJ, et al. Multislice computed tomography for detection of patients with aortic valve stenosis and quantification of severity. J Am Coll Cardiol 2006;47: 1410–7.
3290–5. 7. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63: 2438–88.
4. Oh JK, Taliercio CP, Holmes DR Jr., et al. Prediction of the severity of aortic stenosis
8. Burwash IG, Thomas DD, Sadahiro M, et al.
by Doppler aortic valve area determination: prospective Doppler-catheterization correlation in 100 patients. J Am Coll Cardiol 1988;11: 1227–34.
Dependence of Gorlin formula and continuity equation valve areas on transvalvular volume flow rate in valvular aortic stenosis. Circulation 1994; 89:827–35.
9. Messika-Zeitoun D, Aubry MC, Detaint D, et al. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation 2004;110: 356–62. 10. Pohle K, Maffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001;104:1927–32. 11. Feuchtner GM, Muller S, Grander W, et al. Aortic valve calcification as quantified with multislice computed tomography predicts shortterm clinical outcome in patients with asymptomatic aortic stenosis. J Heart Valve Dis 2006;15: 494–8. 12. Clavel M-A, Pirabot P, Messika-Zeitoun D, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol 2014;64:1202–13. 13. Miller JD, Chu Y, Brooks RM, Richenbacher WE, Pena-Silva R, Heistad DD. Dysregulation of antioxidant mechanisms contributes to increased
1215
1216
Garcia
JACC VOL. 64, NO. 12, 2014
Between a Rock and a Hard Place
SEPTEMBER 23, 2014:1214–6
oxidative stress in calcific aortic valvular stenosis in humans. J Am Coll Cardiol 2008;52: 843–50. 14. Brown JM, O’Brien SM, Wu C, Sikora JA, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg 2009;137:82–90.
15. Yamamoto M, Hayashida K, Mouillet G, et al. Prognostic value of chronic kidney disease after transcatheter aortic valve implantation. J Am Coll Cardiol 2013;62:869–77.
17. Malouf JF, Enriquez-Sarano M, Pellikka PA, et al. Severe pulmonary hypertension in patients with severe aortic valve stenosis: clinical profile and prognostic implications. J Am Coll Cardiol
16. Gjertsson P, Caidahl K, Farasati M, Oden A, Bech-Hanssen O. Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients
2002;40:789–95.
with severe aortic stenosis. J Thorac Cardiovasc Surg 2005;129:890–6.
KEY WORDS aortic stenosis, computed tomography, echocardiography
