Is it ever worth contemplating an aortic valve replacement on patients with low gradient severe aortic stenosis but poor left ventricular function with no contractile reserve?

Subramanian, Hariharan; Kunadian, Babu; Dunning, Joel

doi:10.1510/icvts.2008.175463

Abstract

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether it is worth performing aortic valve replacement in patients with severe aortic stenosis and poor left ventricular function but no contractile reserve on dobutamine stress testing. Altogether 251 papers were identified using the below mentioned search and all major international guidelines were included. Fourteen presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. We conclude that patients with severe aortic stenosis and a contractile reserve of <20% improvement in stroke volume on dobutamine stress testing have a very poor prognosis of only 10–20% at two years. Heart transplant would offer the best chance of survival to those eligible but for those not eligible, a surgical option should not be discounted for selected patients. The American Heart Association guidelines state that prognosis is very poor for either medical or surgical treatment, but the European Society of Cardiology guidelines state that surgery can be performed in these patients but should take into account the clinical condition of the patient. The operative mortality is around 30% and the French Multicentre study on low gradient aortic stenosis has shown that if the patient survives there is likely to be an improvement in symptoms and ejection fraction. Thus, absence of contractile reserve on stress testing does not exclude myocardial recovery after surgery, although it is a strong predictor for operative mortality. It should be noted that surgery has only been reported in very few of these patients to date. B-natriuretic peptide has also been suggested as a further marker of better prognosis in these high-risk patients in one small study.

Evidence-based medicine, Aortic valve stenosis, Congestive heart failure, Thoracic surgery

1. Introduction

A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].

2. Clinical scenario

You have been asked to evaluate a previously very fit 65-year-old ex-mountaineer for aortic valve replacement (AVR). He first presented to the cardiologists in pulmonary oedema two weeks ago although he tells you that he has been getting gradually worse for three years. The transthoracic echo revealed an effective orifice area (EOA) of his aortic valve of 0.7 cm², left ventricular ejection fraction of 30%, and mean transaortic pressure difference of 25 mmHg. The cardiologists performed a dobutamine stress echocardiography (DSE) that revealed a minimal rise in the systolic velocity integral (15%) and no increase in the EOA. The cardiologists feel that he is beyond the point at which an AVR would help him, but would value your opinion.

3. Three-part question

In [Patients with severe aortic stenosis, poor left ventricular function and no reversibility] is an [Aortic Valve Replacement superior to medical therapy] to improve [Survival or symptoms].

4. Search strategy

Medline 1950–Nov 2007.

[exp Aortic Valve Stenosis/OR aortic stenosis.mp] AND [exp Ventricular Dysfunction, Left/OR left ventricular dysfunction.mp OR exp Dobutamine OR Dobutamine stress.mp OR exp Heart Failure, Congestive/] AND [Thoracic Surgery.mp OR exp Thoracic Surgery/OR AVR.mp OR valve replacement.mp].

5. Search outcome

A total of 251 papers were found. In addition, all major guidelines were included and their reference lists searched. Fourteen papers were deemed to represent the best evidence on the topic and are summarized in Table 1 .

Table 1

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Summary of best evidence papers

Author, date and country,	Patient group	Outcomes	Key results	Comments/weaknesses
Study type
(level of evidence)
American College of	Systematic review of a	Guideline	Patients in whom stroke volume fails to	Only 2 references given
Cardiology/American	wide range of issues in	recommendations	increase with dobutamine (<20% increase)	in support of this
Heart Association Clinical	valvular heart disease		appear to have a very poor prognosis with	recommendation
Practice Guideline, (2006),			either medical or surgical therapy
Circulation, J Am Coll	This review updated
Cardiol, USA, [8]	a previous review		Dobutamine stress echocardiography is
	conducted in 1998		reasonable to evaluate patients with low-flow/
Systematic review			low-gradient AS and LV dysfunction.
(level 1a)			(level of evidence: B)
			2. Cardiac catheterization for hemodynamic
			measurements with infusion of dobutamine
			can be useful for evaluation of patients with
			low-flow/low-gradient AS and LV
			dysfunction. (level of evidence: C)
European Society of	Systematic review of	AVR in patients	Patients in whom stroke volume fails to	Only 1 reference given
Cardiology task force	a wide range of issues	with severe aortic	increase with dobutamine (<20% increase)	in support of this
guidelines on management	in valvular heart disease	stenosis and no	appear to have a very poor prognosis with	recommendation
of Valvular Heart disease,		contractile reserve	either medical or surgical therapy.
(2007), Eur Heart J, [9]		on stress testing	Surgery can, nonetheless, be performed
			in these patients but decision-making should take
Systematic review			into account clinical condition (in particular,
(level 1a)			the presence of comorbidity), degree of valve
			calcification, extent of coronary disease, and
			feasibility of revascularisation
The Topas Study, Bergler-Klein	2002–2005, 69 patients	Mortality	9 of 29 who had AVR (31%)	The operative survival
et al., (2007),	with low flow AS		6 of 20 who had AVR with TS AS (30%)	was not explicitly given
Circulation, Austria, [7]	(EOA <0.6 cm²/m²,		3 of 9 who had AVR with PS AS (33%)	for the subgroup with
	mean grad <40 mmHg,			poor contractile
Prospective cohort study	LVEF <40%), grouped		11 of 40 medically treated patients (27%)	reserve
(level 2b)	into truly severe or		2 of 9 medically treated TS AS (22%)
	pseudosevere AS by		9 of 31 medically treated PS AS (29%)	This is (understandably)
	EOA <1.0 cm² on			a small study for the sub-dobutamine
	stress			analyses performed
	Contractile reserve	BNP relationship	19% if BNP >550 pg/ml
	defined as an increase	to 30 days	8% if BNP <550 pg/ml
	of SV >20%	mortality in
		operated AS
	BNP measured at
	regular intervals	Patients with poor	50% mortality in high BNP group
		or no contractile	100% mortality in low BNP group
	Surgery or medical	reserve (n=32)
	therapy at discretion of		1-year survival in patients with poor
	physicians (29 AVR)		contractile reserve is as good as those with
	2-year follow-up		reserve as long as BNP <550 pg/ml
Monin et al., (2001), J Am	Low-dose DSE in 45	Peri-operative	Group I – 8% (2 of 24 patients)	Very small number of
Coll Cardiol, France and	patients with median	mortality	Group II – 50% (3 of 6 patients) (P=0.014)	patients – only 6 patients
Belgium, [3]	age 75, LVEF 29%,			in the group with no
	aortic valve area	Long-term	Group I – 88% (21 of 24 patients) in those	contractile reserve that
Cohort study	0.7 cm² and mean	survival	who had AVR	underwent AVR
(level 2b)	transaortic gradient		Group II – 1 of the 3 survivors died at 3 months.
	26 mmHg.		No data available about the outcome	Observational study
	Patients divided into		of the remaining 2 patients
	2 groups – group I with
	LV contractile reserve	Postoperative	Group I – Marked improvement in functional
	on DSE (n=32) and	functional	class – 17 patients initially in NYHA class
	group II with no LV	improvement	III/IV compared to only 1 patient in class III
	contractile reserve on		at follow-up (P=0.001).
	DSE (n=13).		Group II – Improvement in NYHA functional
	AVR performed in 24		class from IV to III in 1 patient while the other
	patients in group I and		remained in class III
	6 in group II
Nishimura et al., (2002),	32 patients with low-output,	Peri-operative	Group I – 7% – 1 of 15 patients	Very small number of
Circulation, USA, [6]	low-gradient	mortality	Group II – 33% – 2 of 6 patients	patients – only 6 patients
	aortic stenosis and			in the group with no
Cohort study	EF <40% subjected to	Late deaths	Group I – 13.3% – 2 of 15 patients –	contractile reserve that
(level 2b)	Dobutamine stress		both non-cardiac	underwent AVR
	testing in the		Group II – 33% – 2 of 6 patients – both
	catheterization		cardiac – from heart failure at months	Observational study
	laboratory. Based on		25 and 34
	the results of the
	above, 21 patients	Postoperative	Group I – all 12 in NYHA I–II
	underwent AVR.	functional	Group II – 2 in NYHA I–II
	Patients who had AVR	improvement
	divided into 2 groups
	on the basis of
	presence or absence of
	a contractile response
	to dobutamine infusion
	group I (n=15) with
	20% increase in stroke
	volume and group II
	(n=6) with <20% increase
	in stroke volume
Monin et al., (2003),	6 center study with	Peri-operative	Group I – 5% – 3 of 64 patients	Number of patients in the
Circulation, France and	prospective enrolment	mortality	Group II – 32% – 10 of 31 patients	group with no contractile
Belgium, [4]	of 136 patients with			reserve who underwent
	aortic stenosis-median	Long-term	Group I – Estimated 3-year survival of 79%	AVR still small though
Cohort study	aortic valve area of	survival	after AVR, and 20% without AVR	larger than in previous
(level 2b)	0.7 cm², median		Group II – around 35% after AVR,	studies
	transaortic gradient		and 10% without AVR
	of 29 mmHg and			Observational study –
	median cardiac index	Postoperative	Group I – in 84% – 54 of 64 patients	patients not randomized
	of 2.11 l/min/m².	functional	Group II – in 45% – 14 of 31 patients.
	Patients divided into	improvement
	2 groups based on
	DSE – group I (n=92)
	with contractile
	reserve – and group II
	(n=44) with no
	contractile reserve.
	70% of patients in both
	groups had AVR – 64 of 92
	in group I and 31 of
	of 44 in group II
Quere et al., (2006),	66 patients with low	Operative	Group I – 3 of 50 (6%)	Well performed
Circulation, France, [5]	gradient (MPG	Mortality	Group II – 10 of 30 (30%)	prospective cohort
	≤40 mmHg), severe			study (The French
Sub analysis of a	aortic stenosis (AVA	Postoperative	Group I – 96% (44/46) improved by ≥1	Multicentre study on
prospective cohort study	≤1 cm²) with an EF	functional	functional class and 59% (27/46) improved	low gradient AS)
(level 2b)	≤40% prospectively	improvement	by ≥2 functional classes after AVR.
	enrolled in (2)	in those who	Group II – 90% (18/20) improved by ≥1
	underwent AVR after	survived	functional class (P=0.35 versus group I) and
	dobutamine stress		55% (11/20) improved by ≥2 functional
	evaluation.		classes after AVR (P=0.50 versus group I)
	Preoperative contractile
	reserve resent in 46	Postoperative	Group I – LVEF increased from 28±6–47±11%
	patients (group I; 70%)	improvement	(P<0.0001) with a mean increase of 19±10%.
	and absent in 20	in ejection	Group II – LVEF increased from 31±6–48±11%
	patients (group II 30%).	fraction in	(P=0.0001) with a mean increase of 17±11%.
	Left ventricular ejection	those who	Similar postoperative increase in LVEF in
	fraction calculated in all	survived	both groups
	66 patients before AVR
	and after the 30-day	Postoperative	Group I – 92+7% (P=0.63)
	postoperative period.	survival at 2	Group II – 90+5%
	Follow-up clinical data	years assuming
	obtained in all patients	operative
	at a mean interval of	survival
	26±20 months

Author, date and country,	Patient group	Outcomes	Key results	Comments/weaknesses
Study type
(level of evidence)
American College of	Systematic review of a	Guideline	Patients in whom stroke volume fails to	Only 2 references given
Cardiology/American	wide range of issues in	recommendations	increase with dobutamine (<20% increase)	in support of this
Heart Association Clinical	valvular heart disease		appear to have a very poor prognosis with	recommendation
Practice Guideline, (2006),			either medical or surgical therapy
Circulation, J Am Coll	This review updated
Cardiol, USA, [8]	a previous review		Dobutamine stress echocardiography is
	conducted in 1998		reasonable to evaluate patients with low-flow/
Systematic review			low-gradient AS and LV dysfunction.
(level 1a)			(level of evidence: B)
			2. Cardiac catheterization for hemodynamic
			measurements with infusion of dobutamine
			can be useful for evaluation of patients with
			low-flow/low-gradient AS and LV
			dysfunction. (level of evidence: C)
European Society of	Systematic review of	AVR in patients	Patients in whom stroke volume fails to	Only 1 reference given
Cardiology task force	a wide range of issues	with severe aortic	increase with dobutamine (<20% increase)	in support of this
guidelines on management	in valvular heart disease	stenosis and no	appear to have a very poor prognosis with	recommendation
of Valvular Heart disease,		contractile reserve	either medical or surgical therapy.
(2007), Eur Heart J, [9]		on stress testing	Surgery can, nonetheless, be performed
			in these patients but decision-making should take
Systematic review			into account clinical condition (in particular,
(level 1a)			the presence of comorbidity), degree of valve
			calcification, extent of coronary disease, and
			feasibility of revascularisation
The Topas Study, Bergler-Klein	2002–2005, 69 patients	Mortality	9 of 29 who had AVR (31%)	The operative survival
et al., (2007),	with low flow AS		6 of 20 who had AVR with TS AS (30%)	was not explicitly given
Circulation, Austria, [7]	(EOA <0.6 cm²/m²,		3 of 9 who had AVR with PS AS (33%)	for the subgroup with
	mean grad <40 mmHg,			poor contractile
Prospective cohort study	LVEF <40%), grouped		11 of 40 medically treated patients (27%)	reserve
(level 2b)	into truly severe or		2 of 9 medically treated TS AS (22%)
	pseudosevere AS by		9 of 31 medically treated PS AS (29%)	This is (understandably)
	EOA <1.0 cm² on			a small study for the sub-dobutamine
	stress			analyses performed
	Contractile reserve	BNP relationship	19% if BNP >550 pg/ml
	defined as an increase	to 30 days	8% if BNP <550 pg/ml
	of SV >20%	mortality in
		operated AS
	BNP measured at
	regular intervals	Patients with poor	50% mortality in high BNP group
		or no contractile	100% mortality in low BNP group
	Surgery or medical	reserve (n=32)
	therapy at discretion of		1-year survival in patients with poor
	physicians (29 AVR)		contractile reserve is as good as those with
	2-year follow-up		reserve as long as BNP <550 pg/ml
Monin et al., (2001), J Am	Low-dose DSE in 45	Peri-operative	Group I – 8% (2 of 24 patients)	Very small number of
Coll Cardiol, France and	patients with median	mortality	Group II – 50% (3 of 6 patients) (P=0.014)	patients – only 6 patients
Belgium, [3]	age 75, LVEF 29%,			in the group with no
	aortic valve area	Long-term	Group I – 88% (21 of 24 patients) in those	contractile reserve that
Cohort study	0.7 cm² and mean	survival	who had AVR	underwent AVR
(level 2b)	transaortic gradient		Group II – 1 of the 3 survivors died at 3 months.
	26 mmHg.		No data available about the outcome	Observational study
	Patients divided into		of the remaining 2 patients
	2 groups – group I with
	LV contractile reserve	Postoperative	Group I – Marked improvement in functional
	on DSE (n=32) and	functional	class – 17 patients initially in NYHA class
	group II with no LV	improvement	III/IV compared to only 1 patient in class III
	contractile reserve on		at follow-up (P=0.001).
	DSE (n=13).		Group II – Improvement in NYHA functional
	AVR performed in 24		class from IV to III in 1 patient while the other
	patients in group I and		remained in class III
	6 in group II
Nishimura et al., (2002),	32 patients with low-output,	Peri-operative	Group I – 7% – 1 of 15 patients	Very small number of
Circulation, USA, [6]	low-gradient	mortality	Group II – 33% – 2 of 6 patients	patients – only 6 patients
	aortic stenosis and			in the group with no
Cohort study	EF <40% subjected to	Late deaths	Group I – 13.3% – 2 of 15 patients –	contractile reserve that
(level 2b)	Dobutamine stress		both non-cardiac	underwent AVR
	testing in the		Group II – 33% – 2 of 6 patients – both
	catheterization		cardiac – from heart failure at months	Observational study
	laboratory. Based on		25 and 34
	the results of the
	above, 21 patients	Postoperative	Group I – all 12 in NYHA I–II
	underwent AVR.	functional	Group II – 2 in NYHA I–II
	Patients who had AVR	improvement
	divided into 2 groups
	on the basis of
	presence or absence of
	a contractile response
	to dobutamine infusion
	group I (n=15) with
	20% increase in stroke
	volume and group II
	(n=6) with <20% increase
	in stroke volume
Monin et al., (2003),	6 center study with	Peri-operative	Group I – 5% – 3 of 64 patients	Number of patients in the
Circulation, France and	prospective enrolment	mortality	Group II – 32% – 10 of 31 patients	group with no contractile
Belgium, [4]	of 136 patients with			reserve who underwent
	aortic stenosis-median	Long-term	Group I – Estimated 3-year survival of 79%	AVR still small though
Cohort study	aortic valve area of	survival	after AVR, and 20% without AVR	larger than in previous
(level 2b)	0.7 cm², median		Group II – around 35% after AVR,	studies
	transaortic gradient		and 10% without AVR
	of 29 mmHg and			Observational study –
	median cardiac index	Postoperative	Group I – in 84% – 54 of 64 patients	patients not randomized
	of 2.11 l/min/m².	functional	Group II – in 45% – 14 of 31 patients.
	Patients divided into	improvement
	2 groups based on
	DSE – group I (n=92)
	with contractile
	reserve – and group II
	(n=44) with no
	contractile reserve.
	70% of patients in both
	groups had AVR – 64 of 92
	in group I and 31 of
	of 44 in group II
Quere et al., (2006),	66 patients with low	Operative	Group I – 3 of 50 (6%)	Well performed
Circulation, France, [5]	gradient (MPG	Mortality	Group II – 10 of 30 (30%)	prospective cohort
	≤40 mmHg), severe			study (The French
Sub analysis of a	aortic stenosis (AVA	Postoperative	Group I – 96% (44/46) improved by ≥1	Multicentre study on
prospective cohort study	≤1 cm²) with an EF	functional	functional class and 59% (27/46) improved	low gradient AS)
(level 2b)	≤40% prospectively	improvement	by ≥2 functional classes after AVR.
	enrolled in (2)	in those who	Group II – 90% (18/20) improved by ≥1
	underwent AVR after	survived	functional class (P=0.35 versus group I) and
	dobutamine stress		55% (11/20) improved by ≥2 functional
	evaluation.		classes after AVR (P=0.50 versus group I)
	Preoperative contractile
	reserve resent in 46	Postoperative	Group I – LVEF increased from 28±6–47±11%
	patients (group I; 70%)	improvement	(P<0.0001) with a mean increase of 19±10%.
	and absent in 20	in ejection	Group II – LVEF increased from 31±6–48±11%
	patients (group II 30%).	fraction in	(P=0.0001) with a mean increase of 17±11%.
	Left ventricular ejection	those who	Similar postoperative increase in LVEF in
	fraction calculated in all	survived	both groups
	66 patients before AVR
	and after the 30-day	Postoperative	Group I – 92+7% (P=0.63)
	postoperative period.	survival at 2	Group II – 90+5%
	Follow-up clinical data	years assuming
	obtained in all patients	operative
	at a mean interval of	survival
	26±20 months

Table 1

Open in new tab

Summary of best evidence papers

Author, date and country,	Patient group	Outcomes	Key results	Comments/weaknesses
Study type
(level of evidence)
American College of	Systematic review of a	Guideline	Patients in whom stroke volume fails to	Only 2 references given
Cardiology/American	wide range of issues in	recommendations	increase with dobutamine (<20% increase)	in support of this
Heart Association Clinical	valvular heart disease		appear to have a very poor prognosis with	recommendation
Practice Guideline, (2006),			either medical or surgical therapy
Circulation, J Am Coll	This review updated
Cardiol, USA, [8]	a previous review		Dobutamine stress echocardiography is
	conducted in 1998		reasonable to evaluate patients with low-flow/
Systematic review			low-gradient AS and LV dysfunction.
(level 1a)			(level of evidence: B)
			2. Cardiac catheterization for hemodynamic
			measurements with infusion of dobutamine
			can be useful for evaluation of patients with
			low-flow/low-gradient AS and LV
			dysfunction. (level of evidence: C)
European Society of	Systematic review of	AVR in patients	Patients in whom stroke volume fails to	Only 1 reference given
Cardiology task force	a wide range of issues	with severe aortic	increase with dobutamine (<20% increase)	in support of this
guidelines on management	in valvular heart disease	stenosis and no	appear to have a very poor prognosis with	recommendation
of Valvular Heart disease,		contractile reserve	either medical or surgical therapy.
(2007), Eur Heart J, [9]		on stress testing	Surgery can, nonetheless, be performed
			in these patients but decision-making should take
Systematic review			into account clinical condition (in particular,
(level 1a)			the presence of comorbidity), degree of valve
			calcification, extent of coronary disease, and
			feasibility of revascularisation
The Topas Study, Bergler-Klein	2002–2005, 69 patients	Mortality	9 of 29 who had AVR (31%)	The operative survival
et al., (2007),	with low flow AS		6 of 20 who had AVR with TS AS (30%)	was not explicitly given
Circulation, Austria, [7]	(EOA <0.6 cm²/m²,		3 of 9 who had AVR with PS AS (33%)	for the subgroup with
	mean grad <40 mmHg,			poor contractile
Prospective cohort study	LVEF <40%), grouped		11 of 40 medically treated patients (27%)	reserve
(level 2b)	into truly severe or		2 of 9 medically treated TS AS (22%)
	pseudosevere AS by		9 of 31 medically treated PS AS (29%)	This is (understandably)
	EOA <1.0 cm² on			a small study for the sub-dobutamine
	stress			analyses performed
	Contractile reserve	BNP relationship	19% if BNP >550 pg/ml
	defined as an increase	to 30 days	8% if BNP <550 pg/ml
	of SV >20%	mortality in
		operated AS
	BNP measured at
	regular intervals	Patients with poor	50% mortality in high BNP group
		or no contractile	100% mortality in low BNP group
	Surgery or medical	reserve (n=32)
	therapy at discretion of		1-year survival in patients with poor
	physicians (29 AVR)		contractile reserve is as good as those with
	2-year follow-up		reserve as long as BNP <550 pg/ml
Monin et al., (2001), J Am	Low-dose DSE in 45	Peri-operative	Group I – 8% (2 of 24 patients)	Very small number of
Coll Cardiol, France and	patients with median	mortality	Group II – 50% (3 of 6 patients) (P=0.014)	patients – only 6 patients
Belgium, [3]	age 75, LVEF 29%,			in the group with no
	aortic valve area	Long-term	Group I – 88% (21 of 24 patients) in those	contractile reserve that
Cohort study	0.7 cm² and mean	survival	who had AVR	underwent AVR
(level 2b)	transaortic gradient		Group II – 1 of the 3 survivors died at 3 months.
	26 mmHg.		No data available about the outcome	Observational study
	Patients divided into		of the remaining 2 patients
	2 groups – group I with
	LV contractile reserve	Postoperative	Group I – Marked improvement in functional
	on DSE (n=32) and	functional	class – 17 patients initially in NYHA class
	group II with no LV	improvement	III/IV compared to only 1 patient in class III
	contractile reserve on		at follow-up (P=0.001).
	DSE (n=13).		Group II – Improvement in NYHA functional
	AVR performed in 24		class from IV to III in 1 patient while the other
	patients in group I and		remained in class III
	6 in group II
Nishimura et al., (2002),	32 patients with low-output,	Peri-operative	Group I – 7% – 1 of 15 patients	Very small number of
Circulation, USA, [6]	low-gradient	mortality	Group II – 33% – 2 of 6 patients	patients – only 6 patients
	aortic stenosis and			in the group with no
Cohort study	EF <40% subjected to	Late deaths	Group I – 13.3% – 2 of 15 patients –	contractile reserve that
(level 2b)	Dobutamine stress		both non-cardiac	underwent AVR
	testing in the		Group II – 33% – 2 of 6 patients – both
	catheterization		cardiac – from heart failure at months	Observational study
	laboratory. Based on		25 and 34
	the results of the
	above, 21 patients	Postoperative	Group I – all 12 in NYHA I–II
	underwent AVR.	functional	Group II – 2 in NYHA I–II
	Patients who had AVR	improvement
	divided into 2 groups
	on the basis of
	presence or absence of
	a contractile response
	to dobutamine infusion
	group I (n=15) with
	20% increase in stroke
	volume and group II
	(n=6) with <20% increase
	in stroke volume
Monin et al., (2003),	6 center study with	Peri-operative	Group I – 5% – 3 of 64 patients	Number of patients in the
Circulation, France and	prospective enrolment	mortality	Group II – 32% – 10 of 31 patients	group with no contractile
Belgium, [4]	of 136 patients with			reserve who underwent
	aortic stenosis-median	Long-term	Group I – Estimated 3-year survival of 79%	AVR still small though
Cohort study	aortic valve area of	survival	after AVR, and 20% without AVR	larger than in previous
(level 2b)	0.7 cm², median		Group II – around 35% after AVR,	studies
	transaortic gradient		and 10% without AVR
	of 29 mmHg and			Observational study –
	median cardiac index	Postoperative	Group I – in 84% – 54 of 64 patients	patients not randomized
	of 2.11 l/min/m².	functional	Group II – in 45% – 14 of 31 patients.
	Patients divided into	improvement
	2 groups based on
	DSE – group I (n=92)
	with contractile
	reserve – and group II
	(n=44) with no
	contractile reserve.
	70% of patients in both
	groups had AVR – 64 of 92
	in group I and 31 of
	of 44 in group II
Quere et al., (2006),	66 patients with low	Operative	Group I – 3 of 50 (6%)	Well performed
Circulation, France, [5]	gradient (MPG	Mortality	Group II – 10 of 30 (30%)	prospective cohort
	≤40 mmHg), severe			study (The French
Sub analysis of a	aortic stenosis (AVA	Postoperative	Group I – 96% (44/46) improved by ≥1	Multicentre study on
prospective cohort study	≤1 cm²) with an EF	functional	functional class and 59% (27/46) improved	low gradient AS)
(level 2b)	≤40% prospectively	improvement	by ≥2 functional classes after AVR.
	enrolled in (2)	in those who	Group II – 90% (18/20) improved by ≥1
	underwent AVR after	survived	functional class (P=0.35 versus group I) and
	dobutamine stress		55% (11/20) improved by ≥2 functional
	evaluation.		classes after AVR (P=0.50 versus group I)
	Preoperative contractile
	reserve resent in 46	Postoperative	Group I – LVEF increased from 28±6–47±11%
	patients (group I; 70%)	improvement	(P<0.0001) with a mean increase of 19±10%.
	and absent in 20	in ejection	Group II – LVEF increased from 31±6–48±11%
	patients (group II 30%).	fraction in	(P=0.0001) with a mean increase of 17±11%.
	Left ventricular ejection	those who	Similar postoperative increase in LVEF in
	fraction calculated in all	survived	both groups
	66 patients before AVR
	and after the 30-day	Postoperative	Group I – 92+7% (P=0.63)
	postoperative period.	survival at 2	Group II – 90+5%
	Follow-up clinical data	years assuming
	obtained in all patients	operative
	at a mean interval of	survival
	26±20 months

Author, date and country,	Patient group	Outcomes	Key results	Comments/weaknesses
Study type
(level of evidence)
American College of	Systematic review of a	Guideline	Patients in whom stroke volume fails to	Only 2 references given
Cardiology/American	wide range of issues in	recommendations	increase with dobutamine (<20% increase)	in support of this
Heart Association Clinical	valvular heart disease		appear to have a very poor prognosis with	recommendation
Practice Guideline, (2006),			either medical or surgical therapy
Circulation, J Am Coll	This review updated
Cardiol, USA, [8]	a previous review		Dobutamine stress echocardiography is
	conducted in 1998		reasonable to evaluate patients with low-flow/
Systematic review			low-gradient AS and LV dysfunction.
(level 1a)			(level of evidence: B)
			2. Cardiac catheterization for hemodynamic
			measurements with infusion of dobutamine
			can be useful for evaluation of patients with
			low-flow/low-gradient AS and LV
			dysfunction. (level of evidence: C)
European Society of	Systematic review of	AVR in patients	Patients in whom stroke volume fails to	Only 1 reference given
Cardiology task force	a wide range of issues	with severe aortic	increase with dobutamine (<20% increase)	in support of this
guidelines on management	in valvular heart disease	stenosis and no	appear to have a very poor prognosis with	recommendation
of Valvular Heart disease,		contractile reserve	either medical or surgical therapy.
(2007), Eur Heart J, [9]		on stress testing	Surgery can, nonetheless, be performed
			in these patients but decision-making should take
Systematic review			into account clinical condition (in particular,
(level 1a)			the presence of comorbidity), degree of valve
			calcification, extent of coronary disease, and
			feasibility of revascularisation
The Topas Study, Bergler-Klein	2002–2005, 69 patients	Mortality	9 of 29 who had AVR (31%)	The operative survival
et al., (2007),	with low flow AS		6 of 20 who had AVR with TS AS (30%)	was not explicitly given
Circulation, Austria, [7]	(EOA <0.6 cm²/m²,		3 of 9 who had AVR with PS AS (33%)	for the subgroup with
	mean grad <40 mmHg,			poor contractile
Prospective cohort study	LVEF <40%), grouped		11 of 40 medically treated patients (27%)	reserve
(level 2b)	into truly severe or		2 of 9 medically treated TS AS (22%)
	pseudosevere AS by		9 of 31 medically treated PS AS (29%)	This is (understandably)
	EOA <1.0 cm² on			a small study for the sub-dobutamine
	stress			analyses performed
	Contractile reserve	BNP relationship	19% if BNP >550 pg/ml
	defined as an increase	to 30 days	8% if BNP <550 pg/ml
	of SV >20%	mortality in
		operated AS
	BNP measured at
	regular intervals	Patients with poor	50% mortality in high BNP group
		or no contractile	100% mortality in low BNP group
	Surgery or medical	reserve (n=32)
	therapy at discretion of		1-year survival in patients with poor
	physicians (29 AVR)		contractile reserve is as good as those with
	2-year follow-up		reserve as long as BNP <550 pg/ml
Monin et al., (2001), J Am	Low-dose DSE in 45	Peri-operative	Group I – 8% (2 of 24 patients)	Very small number of
Coll Cardiol, France and	patients with median	mortality	Group II – 50% (3 of 6 patients) (P=0.014)	patients – only 6 patients
Belgium, [3]	age 75, LVEF 29%,			in the group with no
	aortic valve area	Long-term	Group I – 88% (21 of 24 patients) in those	contractile reserve that
Cohort study	0.7 cm² and mean	survival	who had AVR	underwent AVR
(level 2b)	transaortic gradient		Group II – 1 of the 3 survivors died at 3 months.
	26 mmHg.		No data available about the outcome	Observational study
	Patients divided into		of the remaining 2 patients
	2 groups – group I with
	LV contractile reserve	Postoperative	Group I – Marked improvement in functional
	on DSE (n=32) and	functional	class – 17 patients initially in NYHA class
	group II with no LV	improvement	III/IV compared to only 1 patient in class III
	contractile reserve on		at follow-up (P=0.001).
	DSE (n=13).		Group II – Improvement in NYHA functional
	AVR performed in 24		class from IV to III in 1 patient while the other
	patients in group I and		remained in class III
	6 in group II
Nishimura et al., (2002),	32 patients with low-output,	Peri-operative	Group I – 7% – 1 of 15 patients	Very small number of
Circulation, USA, [6]	low-gradient	mortality	Group II – 33% – 2 of 6 patients	patients – only 6 patients
	aortic stenosis and			in the group with no
Cohort study	EF <40% subjected to	Late deaths	Group I – 13.3% – 2 of 15 patients –	contractile reserve that
(level 2b)	Dobutamine stress		both non-cardiac	underwent AVR
	testing in the		Group II – 33% – 2 of 6 patients – both
	catheterization		cardiac – from heart failure at months	Observational study
	laboratory. Based on		25 and 34
	the results of the
	above, 21 patients	Postoperative	Group I – all 12 in NYHA I–II
	underwent AVR.	functional	Group II – 2 in NYHA I–II
	Patients who had AVR	improvement
	divided into 2 groups
	on the basis of
	presence or absence of
	a contractile response
	to dobutamine infusion
	group I (n=15) with
	20% increase in stroke
	volume and group II
	(n=6) with <20% increase
	in stroke volume
Monin et al., (2003),	6 center study with	Peri-operative	Group I – 5% – 3 of 64 patients	Number of patients in the
Circulation, France and	prospective enrolment	mortality	Group II – 32% – 10 of 31 patients	group with no contractile
Belgium, [4]	of 136 patients with			reserve who underwent
	aortic stenosis-median	Long-term	Group I – Estimated 3-year survival of 79%	AVR still small though
Cohort study	aortic valve area of	survival	after AVR, and 20% without AVR	larger than in previous
(level 2b)	0.7 cm², median		Group II – around 35% after AVR,	studies
	transaortic gradient		and 10% without AVR
	of 29 mmHg and			Observational study –
	median cardiac index	Postoperative	Group I – in 84% – 54 of 64 patients	patients not randomized
	of 2.11 l/min/m².	functional	Group II – in 45% – 14 of 31 patients.
	Patients divided into	improvement
	2 groups based on
	DSE – group I (n=92)
	with contractile
	reserve – and group II
	(n=44) with no
	contractile reserve.
	70% of patients in both
	groups had AVR – 64 of 92
	in group I and 31 of
	of 44 in group II
Quere et al., (2006),	66 patients with low	Operative	Group I – 3 of 50 (6%)	Well performed
Circulation, France, [5]	gradient (MPG	Mortality	Group II – 10 of 30 (30%)	prospective cohort
	≤40 mmHg), severe			study (The French
Sub analysis of a	aortic stenosis (AVA	Postoperative	Group I – 96% (44/46) improved by ≥1	Multicentre study on
prospective cohort study	≤1 cm²) with an EF	functional	functional class and 59% (27/46) improved	low gradient AS)
(level 2b)	≤40% prospectively	improvement	by ≥2 functional classes after AVR.
	enrolled in (2)	in those who	Group II – 90% (18/20) improved by ≥1
	underwent AVR after	survived	functional class (P=0.35 versus group I) and
	dobutamine stress		55% (11/20) improved by ≥2 functional
	evaluation.		classes after AVR (P=0.50 versus group I)
	Preoperative contractile
	reserve resent in 46	Postoperative	Group I – LVEF increased from 28±6–47±11%
	patients (group I; 70%)	improvement	(P<0.0001) with a mean increase of 19±10%.
	and absent in 20	in ejection	Group II – LVEF increased from 31±6–48±11%
	patients (group II 30%).	fraction in	(P=0.0001) with a mean increase of 17±11%.
	Left ventricular ejection	those who	Similar postoperative increase in LVEF in
	fraction calculated in all	survived	both groups
	66 patients before AVR
	and after the 30-day	Postoperative	Group I – 92+7% (P=0.63)
	postoperative period.	survival at 2	Group II – 90+5%
	Follow-up clinical data	years assuming
	obtained in all patients	operative
	at a mean interval of	survival
	26±20 months

6. Discussion

Low gradient low flow aortic stenosis is defined by the American Heart Association as aortic stenosis with an effective aortic area <1 cm², left ventricular ejection fraction <40% and mean transaortic pressure gradient of <30 mmHg. Assessment by dobutamine stress testing is essential to verify that the reduced effective orifice area is in fact severe rather than an effect of low flow on a mild or moderately stenosed valve [2]. Contractile reserve on dobutamine stress testing is defined by an increase in the systolic velocity integral or stroke volume by at least 20% during dobutamine infusion. Aortic valve replacement is recommended by the AHA for patients with low gradient, low flow aortic stenosis with contractile reserve (Class I: level of evidence C).

For patients without contractile reserve, the most comprehensive studies have been performed by the French Multicentre study on low gradient aortic stenosis by Quere, Monin and colleagues. In the study by Monin et al. in 2001 [3], the perioperative mortality of patients without contractile reserve undergoing AVR was about 50% but the number of patients in this subgroup was only six, and no definitive conclusions could be reached. In their largest study published in 2003 [4] involving 136 patients, Kaplan–Meier analysis of patients without contractile reserve showed a 2-year survival rate of 35% of those undergoing AVR and 15% treated medically. The most recent report by Quere et al. [5] where 20 patients without contractile reserve had an AVR, concluded that LV dysfunction and functional status can improve significantly after AVR even in patients with no contractile reserve although their operative mortality is around 30%. In a study by Nishimura et al. [6], about one-third of the patients without contractile reserve died perioperatively while another third died at months 25 and 34. Again the number of patients in this subgroup without contractile reserve who underwent AVR was very small – 6, statistically not significant.

The Topas Study (Truly Or Pseudosevere Aortic Stenosis) [7] found in a cohort study of 69 patients, of whom 29 had an aortic valve replacement that poor contractile reserve was not a surgical predictor of mortality compared to patients with contractile reserve as long as the BNP was <550 pg/ml. This was, however, a very small subset analysis.

The American Heart Association guidelines state that the mortality is very high in patients with no contractile reserve either with or without surgery. The European Society of Cardiology agrees with this but also states that surgery can be performed but should take into account the patient's co-morbidities [8,9].

7. Clinical bottom line

It is clear that patients with severe aortic stenosis and a contractile reserve of <20% improvement in stroke volume on dobutamine stress testing have a very poor prognosis of only 10–20% at two years. Heart transplant would offer the best chance of survival to those eligible but for those not eligible, a surgical option should not be discounted for selected patients. The operative mortality is, however, around 30% but the French Multicentre study on low gradient aortic stenosis has shown that if the patient survives there is likely to be an improvement in symptoms and ejection fraction. Thus, absence of contractile reserve on stress testing does not exclude myocardial recovery after surgery, although it is a strong predictor for operative mortality.

It should be noted that surgery has only been reported in very few of these patients to date. B-natriuretic peptide has also been suggested as a further marker of better prognosis in these high-risk patients in one small study.

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Article Contents

Is it ever worth contemplating an aortic valve replacement on patients with low gradient severe aortic stenosis but poor left ventricular function with no contractile reserve?

Abstract

1. Introduction

2. Clinical scenario

3. Three-part question

4. Search strategy

5. Search outcome

6. Discussion

7. Clinical bottom line

References

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Article Contents

Is it ever worth contemplating an aortic valve replacement on patients with low gradient severe aortic stenosis but poor left ventricular function with no contractile reserve? Free

Abstract

1. Introduction

2. Clinical scenario

3. Three-part question

4. Search strategy

5. Search outcome

6. Discussion

7. Clinical bottom line

References

Citations

Views

Altmetric

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Is it ever worth contemplating an aortic valve replacement on patients with low gradient severe aortic stenosis but poor left ventricular function with no contractile reserve?