Transcript Natural history of Aortic stenosis

Dr Charles T Itty
Interventional Cardiology Fellow
John Hunter Hospital
Newcastle
 Calcareous (calcific)
aortic valve stenosis
was first described by
Mockeberg in 1904.
Monckeberg, J. G. (1904).
Virchows Archiv fur athologische
Anatomie und Physiology undfur
Klinische Medizin, 176, 472.
Dry, T. J., and Willius F. A.: Am. Heart Journal, 17:138-157 (Feb.), 1939.
Dry, T. J., and Willius F. A.
Am. Heart Journal, 17:138-157
(Feb.), 1939.
 Causes of death (n=106):
 Congestive heart failure, 32 patients (3o.5%)
 Sudden death, 18 patients (17%)
 Infective endocarditis, 5 patients (4.7%)
 Acute coronary occlusion, 1 patient (0.9%)
 Non cardiac cause, 50 patients (47%).
Dry, T. J., and Willius F. A.: Am. Heart Journal, 17:138-157 (Feb.), 1939.
 ‘Majority of patients who died when the syndrome of
congestive heart failure was present responded to
therapy in a rather disappointing manner ...’
 ‘Symptoms are likely to remain in abeyance for many
years, but with the onset of myocardial failure the
outlook becomes serious’.
Dry, T. J., and Willius F. A.: Am. Heart Journal, 17:138-157 (Feb.), 1939.
 1947 - Zimmerman discovered the technique of left
heart cardiac catheterization.
 He was later awarded the Nobel Prize for combined
cardiac catheterization.
 The evaluation of the natural history of aortic stenosis
has been difficult, because
 the development of objective means for assessment of
its severity by left heart catheterization, and
 the initial attempts at operative treatment,
occurred almost simultaneously.
 ‘The natural course of aortic stenosis was assembled
 from clinical and postmortem studies largely from
before 1955, and
 from a few more recent analyses that are supported by
hemodynamic information’.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 Patients included in this analysis:
 Isolated valvular aortic stenosis of rheumatic aetiology.
 Isolated calcific aortic stenosis with no history of
rheumatic fever. (many were considered to have
congenitally bicuspid valve).
 The review focussed primarily on the prognostic
significance of three major symptoms
 angina pectoris,
 syncope and
 symptoms of left ventricular failure.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 Symptoms usually begin during the sixth decade of life
following a long latent period.
 This silent period is marked by
 Progressive stenosis, due to thickening and calcification
 And/or by progressive myocardial dysfunction.
 Once symptoms develop, the average course is short,
culminating in death at an average age of 63 years.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 The average durations of various symptoms were:
 Angina pectoris: 3 years,
 Syncope: 3 years,
 Dyspnea: 2 years and
 Congestive heart failure: 1.5 to 2 years.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 Congestive heart failure: 50-60%.
 Infective endocarditis: 15-20%.
 Sudden death: 15-20%.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 Tended to occur in patients with symptoms.
 65-80% of patients had history of angina pectoris,
heart failure, or syncope.
 12-20% of patients had evidence of old or recent
myocardial infarction.
 Only 3-5% of deaths appear to occur suddenly in
patients without symptoms.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 Surgical replacement of the aortic valve with a ball-
valve prosthesis or aortic valve homograft:
 Early mortality was approximately 10%.
 Total mortality had averaged 23%.
 In more than 80% of the survivors, the clinical result
achieved has been described as good or excellent.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
Iung B et al. Eur Heart J. 2003 Jul;24(13):1231-43.
 Aortic stenosis in the 21st century is the result of 2
main pathological processes*
 Congenital bicuspid aortic valves and
 Atherosclerotic/calcific aortic valves.
 The present patient population is older.
 They have more associated coronary artery disease.
 There has been improvements in the treatment of
heart failure and infective endocarditis.
* Alpert JS. Am J Med. 2010 Oct;123(10):875-6.
 They are present in 1% of all infants born (US data)#.
 It is estimated that only 1 in 50 of children have
clinically significant valve disease by adolescence*.
 In the Olmsted County series (n=212), 27% of adults
with BAV at baseline required cardiovascular surgery
at 20 years of follow-up0.
 They can develop clinically important aortic stenosis
during late middle life, usually between the 5th and 6th
decades of life#.
#Alpert
JS. Am J Med. 2010 Oct;123(10):875-6.
*Bonow RO et al. J Am Coll Cardiol 2006;48:e1–148.
0Samuel C et al. J. Am. Coll. Cardiol. 2010;55;2789-2800
 Degenerative calcific aortic stenosis usually manifests
in individuals older than 75 years and occurs most
frequently in males.
 Often, these elderly patients have a number of
associated co-morbid conditions which increases the
surgical risk.
Townsend CM, et al. Sabiston Textbook of Surgery. 18th ed. Saunders; 2008:1841-1844.
 An estimated 46,397 aortic valve replacements (AVR)
were performed.
 In-hospital mortality occurred in
 4.3% of first-time isolated AVR and
 6.4% overall.
Astor BC et al. Ann Thorac Surg. 2000 Dec;70(6):1939-45.
 STS U.S. cardiac surgery database, 1997
 Patients in NYHA classes I or II had an operative
mortality of <2%
 NYHA III 3·7% and
 NYHA IV 7·0%
European Heart Journal (2002) 23, 1417–1421
 Can we generalize the results of the earlier
studies to the current patient population ?
 Retrospective study of
 252 operated and
 47 unoperated patients (who refused surgery)
with isolated aortic valve disease.
 AVR was recommended to all patients based on
clinical and hemodynamic data.
Circulation 1982; 66: 1105–10.
Circulation 1982; 66: 1105–10.
Schwarz F et al. The effect
of aortic valve replacement
on survival. Circulation
1982; 66: 1105–10.
 362 patients with severe aortic stenosis who were
screened and did not meet the inclusion/exclusion
criteria for TAVI trial.
 Group 1 (medical): 274 (75.7%), (64.6% had BAV).
 Group 2 (surgical): 88 (24.3%).
Circulation. 2010;122[suppl 1]:S37–S42.
Circulation. 2010;122[suppl 1]:S37–S42.
Circulation. 2010;122[suppl
1]:S37–S42.
 Medical/BAV
group: Death
 37.2% by 1 year
 53.4% by 2 years.
Circulation. 2010;122[suppl 1]:S37–S42.
 Severe aortic stenosis
 Aortic-valve area <0.8 cm2
 Mean aortic-valve gradient of 40 mm Hg or more or
 Peak aortic-jet velocity of 4.0 m/s or more.
 All patients had NYHA class II, III or IV symptoms.
Leon MB et al. (PARTNER Trial). NEJM. 363(17):1597-607, 2010 Oct 21.
 Standard medical therapy (including BAV done in
83.8% patients) did not alter the natural history of
severe aortic stenosis.
 At the end of 1 year:
 Rate of death from any cause was 50.7% and
 Rate of death from cardiovascular causes was 44.6%.
Leon MB et al. (PARTNER Trial). NEJM. 363(17):1597-607, 2010 Oct 21.
 ‘One of the clearest decisions for a doctor is to
recommend valve replacement for individuals with
severe symptomatic aortic stenosis’.
 ‘Such patients have a dire outlook, with three-quarters
dying within 3 years of symptom onset’.
 ‘Aortic valve replacement can be withheld in such
patients only when compelling contraindications exist’.
Aortic stenosis. Blase A Carabello, Walter J Paulus. Lancet 2009; 373: 956–66
 Many patients with limited or no symptoms yet
hemodynamically significant aortic stenosis are being
identified with the routine use of echo and cardiac
cath.
 The dilemma is how best to treat these patients.
 180 patients with valvular AS followed up for 25 years.
 They reported that sudden death:
 occurred "rarely" in totally asymptomatic patients and
 was often preceded by the development of symptoms.
Contratto AW eta al. Ann Intern Med 1937; 10:1636-53
 Sudden death tended to occur in patients with
symptoms.
 Only 3 to 5% of the sudden deaths in acquired AS
appear to occur in patients without symptoms.
 It was proposed that patients with acquired valvular AS
have surgery deferred until the onset of symptoms.
Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):V61-67
 Retrospective review of 73 patients with aortic
stenosis.
 17 asymptomatic or mildly symptomatic patients with
severe AS or combined AS+AR.
 None of the patients died or required valve surgery
during the first 2 years.
 At 5 years, 75% were event free (alive and not had
surgery) and 94% survived.
Turina J et al. Eur Heart J 1987; 8:471-83
 They concluded that asymptomatic or minimally
symptomatic patients with severe AS are at low risk of
death and that surgical treatment can be postponed
until "marked symptoms" appear.
Turina J et al. Eur Heart J 1987; 8:471-83
 51 asymptomatic patients with severe AS.
 Followed up for a mean of 17 months.
 21 (41%) patients became symptomatic.
 Only two died of cardiac causes and both had become
symptomatic for at least 3 months prior.
 The conclusion was, that patients be followed up until
symptoms develop.
Kelly TA et al. Am J Cardiol 1988; 61:123-30
 113 asymptomatic patients with significant AS.
 Mean follow-up was 20 months.
 Three deaths:
 2 sudden deaths
 1 congestive heart failure.
 In each case, the development of symptoms preceded
death by at least 3 months.
 Conclusion was that asymptomatic AS patients be
followed up closely until symptoms develop.
Pellikka P etal. J Am Coll Cardiol 1990; 15:1012-17
 Asymptomatic patients are at low risk for
complications or mortality.
 Risk of sudden death is <1% per year.
 Surgical therapy should be considered as soon as the
patient develops symptoms.
Steven J et al. Chest 1998;113;1109-1114
 Undertaking AVR in all asymptomatic patients would
only benefit the <1% who would die suddenly before
symptoms develop, while exposing all to the risks of
surgery and prosthetic valve related complications.
 Therefore, the thrust should be to define a high-risk
group of asymptomatic patients in whom risk of no
intervention is higher than that of AVR.
Aortic stenosis. Blase A Carabello, Walter J Paulus. Lancet 2009; 373: 956–66
 Risk stratification might incorporate
 Jet velocity,
 Progression of valvular narrowing,
 Response to exercise testing,
 Co-morbidity,
 Abnormally raised biomarkers,
 Presence of ventricular dysfunction,
 Degree of valvular calcification etc.
Aortic stenosis. Blase A Carabello, Walter J Paulus. Lancet 2009; 373: 956–66
 128 consecutive patients with asymptomatic, severe
aortic stenosis.
 Followed up for a mean of 22±18 months.
 End point: Death (8 patients) or valve replacement
necessitated by the development of symptoms (59
patients).
N Engl J Med 2000; 343:611-7.
N Engl J Med
2000; 343:611-7.
 Event-free survival was
 67±5% at one year,
 56±5% at 2 years and
 33±5% at 4 years.
 Five of the six deaths from cardiac disease were
preceded by symptoms.
 One patient had sudden death while still
asymptomatic.
N Engl J Med 2000; 343:611-7.
N Engl J Med 2000; 343:611-7.
 The rate of
progression of
aortic-jet velocity
was significantly
higher in patients
who had cardiac
events. (0.45±0.38
vs. 0.14±0.18 m per
second per year,
P<0.001)
N Engl J Med 2000; 343:611-7.
 In asymptomatic patients with aortic stenosis, it
appears to be relatively safe to delay surgery until
symptoms develop.
 The presence of moderate or severe valvular
calcification, together with a rapid increase in aorticjet velocity, identifies patients with a very poor
prognosis. These patients should be considered for
early valve replacement.
N Engl J Med 2000; 343:611-7.
 622 patients with asymptomatic AS with mean follow
up of 5.4±4.0 years.
 Peak systolic velocity ≥ 4 m/s.
Circulation. 2005;111:3290-3295.
 Predictors of
symptom
development
 AV area
 LVH.
Circulation.
2005;111:3290-3295.
 Predictors of all-
cause mortality.
 Age
 CRF
 Inactivity
 AV velocity
Circulation.
2005;111:3290-3295.
 Most patients with asymptomatic, hemodynamically
significant AS will develop symptoms within 5 years.
 Sudden death without preceding symptoms occurred
in 11 (4.1%) i.e. ≈1%/y.
 Patients with peak velocity ≥4.5 m/s had a higher
likelihood of developing symptoms (relative risk, 1.34)
or having surgery or cardiac death (relative risk, 1.48).
Circulation. 2005;111:3290-3295.
 107 patients with asymptomatic aortic stenosis
followed up for 24 months.
 Predefined end points:
 Death or
 AVR if symptoms or positive EST.
Circulation. 2009;120:69-75.
Circulation. 2009;120:69-75.
 Score=[peak velocity (m/s)x2]+(natural logarithm of
B-type natriuretic peptidex1.5)+1.5 (if female sex).
 Event-free survival after 20 months was 80% for
patients within the first score quartile compared with
only 7% for the fourth quartile.
Circulation. 2009;120:69-75.
 116 consecutive asymptomatic patients with median
follow up of 41 months.
 Very severe isolated aortic stenosis defined by a peak
aortic jet velocity (AV-Vel)≥5.0 m/s.
 End points: Cardiac death or indication for aortic valve
replacement according to the accepted guidelines.
Circulation. 2010;121:151-156.
96 events
 AVR in 90 patients and
 cardiac deaths in 6 patients.
 Sudden death without symptoms (n=1).
 Congestive heart failure (n=4)
 Myocardial infarction (n=1).
Circulation. 2010;121:151-156.
Circulation. 2010;121:151-156.
Circulation. 2010;121:151-156.
 Patients with asymptomatic very severe aortic stenosis
have a poor prognosis with a high event rate and a risk
of rapid functional deterioration.
 Early elective valve replacement surgery should
therefore be considered in these patients.
Circulation. 2010;121:151-156.
 The peak gradient changed by +12 mm Hg/yr (-10 to
+34 mm Hg) and the
 mean gradient changed by +8 mm Hg/yr (-7 to +23
mm Hg).
 Mean reduction in aortic valve area of -0.1 cm2/yr (0.0
to -0.5 cm2).
J Am Coll Cardiol 1989; 13:545-50
 Mean interval of 25 months,
 Peak gradient increased to 44±16 mm Hg.
 Average increase of 4.8 mm Hg/yr.
Am Heart J 1990; 2:331-38
Steven J et al. Chest 1998;113;1109-1114
 Overall, on average, the aortic valve area decreases by
approximately 0.1 cm2/yr and the peak instantaneous
gradient increases by 10 mm Hg/yr.
 However, in any individual patient, this is highly
variable.
Steven J et al. Chest 1998;113;1109-1114
 There can be identified two distinct types of patients:
 those whose conditions progress slowly and
 others whose conditions progress rapidly.
 There are no reliable clinical predictors to help us
identify into which subgroup an individual patient will
fall.
Steven J et al. Chest 1998;113;1109-1114
J. Am. Coll. Cardiol. 2008;52;e1-e142
J. Am. Coll. Cardiol. 2008;52;e1-e142
J. Am. Coll. Cardiol. 2008;52;e1-e142
J. Am. Coll. Cardiol. 2008;52;e1-e142
 Currently available data suggest that careful weighing
of risk and benefit does not justify the general
recommendation of early elective surgery in
asymptomatic patients with severe aortic stenosis.