Accepted Manuscript Functional Mitral Regurgitation: Current Understanding And Approach To Management Robin A. Ducas, MD Christopher W. White, MD Anthony W. Wassef, MD Ashraf Farag, MD Kapil M. Bhagirath, MD Darren H. Freed, MD James W. Tam, MD PII:
S0828-282X(13)01683-8
DOI:
10.1016/j.cjca.2013.11.022
Reference:
CJCA 1048
To appear in:
Canadian Journal of Cardiology
Received Date: 5 June 2013 Revised Date:
21 November 2013
Accepted Date: 21 November 2013
Please cite this article as: Ducas RA, White CW, Wassef AW, Farag A, Bhagirath KM, Freed DH, Tam JW, Functional Mitral Regurgitation: Current Understanding And Approach To Management, Canadian Journal of Cardiology (2013), doi: 10.1016/j.cjca.2013.11.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
FUNCTIONAL
MITRAL
REGURGITATION:
CURRENT
UNDERSTANDING
RI PT
APPROACH TO MANAGEMENT
Authors: Robin A. Ducas, MD. University of Manitoba Christopher W. White, MD. University of Manitoba
Ashraf Farag, MD. University of Manitoba
Darren H. Freed, MD. University of Manitoba James W. Tam, MD. University of Manitoba’
Dr. Robin A. Ducas
TE D
Corresponding Author:
M AN U
Kapil M. Bhagirath, MD. University of British Columbia
SC
Anthony W. Wassef, MD. University of Manitoba
Room Y3021 Bergen Cardiac Care Centre St. Boniface General Hospital 409 Tache Avenue
EP
Winnipeg, Manitoba R2H 2A6
E-mail: [email protected]
AC C
Phone: (204) 258-1290 Fax: (204) 233-9162
Source of Funding: None
AND
ACCEPTED MANUSCRIPT
Brief Summary:
Functional
mitral
regurgitation
(FMR)
frequently
complicates
ischemic
and
non-ischemic
RI PT
cardiomyopathy, and is associated with increased morbidity and mortality. The pathophysiology of FMR is due primarily to ventricular and sub-valvular apparatus dysfunction causing failure of leaflet coaptation. Echocardiography is the primary modality used in diagnosis and allows for assessment of valvular and
approach
incorporating
medical
therapy
and
of
AC C
EP
TE D
M AN U
resynchronization therapies.
consideration
SC
ventricular structure, and interaction. The optimal management of FMR involves an individualized
Page 2
surgical,
percutaneous,
and
ACCEPTED MANUSCRIPT
Abstract: Functional mitral regurgitation (FMR) is a challenging clinical entity that frequently complicates both
RI PT
ischemic and non-ischemic cardiomyopathy. The underlying pathophysiology of FMR is due primarily to ventricular and sub-valvular apparatus dysfunction causing failure of proper leaflet coaptation. Echocardiography is the primary modality used in diagnosis and characterization of FMR. Echocardiography allows for assessment of valvular and ventricular structures as well as their interaction.
SC
FMR portends a poor prognosis, as it is frequently associated with increased morbidity and mortality. The optimal management of FMR involves an individualized approach that incorporates medical therapy and
M AN U
consideration of surgical, percutaneous, and resynchronization therapies according to the severity of regurgitation, presence of symptoms, option for revascularization, and the degree of ventricular
TE D
remodeling.
Key Words:
EP
1. Functional Mitral Regurgitation 2. Ischemic Mitral Regurgitation
AC C
3. Mitral Valve Disease
ACCEPTED MANUSCRIPT
Introduction Mitral regurgitation is the retrograde flow of blood from the left ventricle (LV) to the left atrium
RI PT
(LA) during systole. Normal function of the mitral valve is a complex process and is dependent upon an intact valve annulus, leaflets, chordae tendonae, papillary muscles, and LV wall working in harmony. Perturbations in any of the aforementioned structures may precipitate mitral
SC
regurgitation. One of the earliest classification systems for mitral valve disease is that of Carpentier.1 In this classification scheme mitral valve regurgitation can be separated into three
M AN U
types: type I (coaptation of the leaflets at the annular plane) due to annular dilatation or leaflet perforation; type II (coaptation beyond the annular plane) secondary to leaflet prolapse or papillary muscle rupture; or type III (coaptation proximal to annular plane) associated with valvular and sub-valvular sclerosis with restricted leaflet motion during diastole and systole (IIIa)
TE D
or restricted leaflet motion predominantly during systole (IIIb) (Figure 1).
Functional mitral regurgitation (FMR) refers to mitral regurgitation that is primarily due to a pathologically dilated LV and mitral annulus or to regional disruptions of the LV and sub-
EP
valvular apparatus. FMR is also referred to as “secondary mitral regurgitation” owing to the fact that it is secondary to myocardial pathology and not a primary disease of the valvular tissues.2
AC C
With respect to the Carpentier classification system, FMR corresponds with the class I or IIIb types. In the literature, “ischemic mitral regurgitation” is a term that is widely used and refers to mitral regurgitation resulting from LV dysfunction due to previous ischemic insults. This is a confusing term as valvular dysfunction is the result of prior infarction and impaired myocardial function, not active or transient ischemia of the papillary muscles.2,3
Page 4
ACCEPTED MANUSCRIPT
Epidemiology As distortion of LV geometry and function are key components in FMR, it is not surprising that
RI PT
FMR is common in both ischemic and non-ischemic cardiomyopathy. The prevalence of moderate to severe FMR has been reported to be up to 60% in ischemic cardiomyopathy and in 40% of cases of non-ischemic cardiomyopathy.4,5 Interestingly, FMR is now the leading cause of
SC
mitral regurgitation in the United States.5
M AN U
FMR is an independent risk factor for death and admission to hospital. When using the proximal iso-volumetric surface area (PISA) method for calculating regurgitant volume (RV) and effective regurgitant orifice (ERO) on echocardiography, there is a clear biological gradient; higher regurgitation results in lower survival. Specifically, patients with FMR and an ERO >0.2cm2 have
TE D
been shown to have higher mortality.6
Pathophysiology
EP
Traditionally FMR has been described as a structurally normal mitral valve with impaired function due to ventricular dilation and dysfunction. However, new insights in to myocardial
AC C
adaptation have also demonstrated abnormalities in the mitral leaflets. Indeed FMR is not simply a disease of ventricular dysfunction and may be better understood in terms of ventricular, subvalvular and valvular interaction and adaptation. 7-9
Left Ventricle
ACCEPTED MANUSCRIPT
In mitral regurgitation, during isovolemic ventricular contraction blood is ejected through the mitral valve into the LA due to a lower pressure gradient, resulting in decreased ventricular
RI PT
volume at the end of isovolemic contraction.2 In severe cases, up to 50% of the LV end diastolic volume is ejected into the LA prior to the opening of the aortic valve.10 Initially this may be well tolerated as the LA enlarges. However, eventually LA compliance is exceeded, resulting in
SC
increased LA pressure and progressive development of pulmonary hypertension.11 A vicious cycle then develops, as the regurgitated blood in the LA returns to the LV during diastole,
M AN U
resulting in LV volume overload and progressive dilatation. With increasing ventricular dilatation there is increased wall stress and worsening of myocardial function, leading in turn to worsening mitral regurgitation.12 Dilation and dysfunction of the LV chamber has long been considered a key component of FMR. Chamber dilation translates into mitral annular dilation, displacement of the papillary muscles, and resultant perturbations in valve leaflet closure. Ventricular
TE D
dyssynchrony also may play a part in FMR by further impairing sub-valvular function.
Ventricular and annular dilatation
EP
The mitral valve annulus, composed of both muscular and fibrous tissue, is a structural component of the LV. A normal mitral valve has a three-dimensional (3D) saddle shape that
AC C
undergoes dynamic changes in area throughout the cardiac cycle, facilitating LV filling and valve closure.13 With dilatation of the LV cavity there is concomitant enlargement and distortion of the mitral annular shape, resulting in a more circular annular configuration. This distortion of the mitral valve shape causes mal-coaptation of the anterior and posterior leaflets and results in valvular incompetence.10,14 Further to the structural abnormalities of the mitral annulus with ventricular dilation, Yiu et al, have demonstrated that loss of systolic annular contraction is
ACCEPTED MANUSCRIPT
associated with a larger ERO and a greater degree of regurgitation.8 Thus both appropriate annular size and configuration, in addition to systolic function are important components valvular
RI PT
competence.
Myocardial function and dyssynchrony
SC
Dyssynchrony of the LV myocardium is proposed to result in dyssynchrony of adjacent papillary muscles, disturbing mitral leaflet closure timing and resulting in FMR. Using tissue Doppler
M AN U
imaging (TDI) in 35 patients with impaired ejection fraction (7mm).26 Both of these methods provide simple assessments of FMR severity; however, these methods are prone to over and underestimation and should be combined with
TE D
quantitative methods.
Quantitative Evaluation of Regurgitation
Classically, severe mitral regurgitation is associated with an ERO >0.4cm2 and RV >60mL.26
EP
However, in FMR, lower values for ERO have been associated with worse outcomes. For example, RV of >30mL and an ERO >0.2cm2, (both classically used to define moderate
AC C
regurgitation), have been associated with a severe reduction in life expectancy at 5 years.6 Though not widely adopted, these findings have lead the European Association of Echocardiography to recommended that these lower values (ERO >0.2cm2, and RV >30mL) be used to define severe FMR (Table 1).14
Mitral Inflow Doppler
ACCEPTED MANUSCRIPT
When a large volume of ventricular blood is regurgitated into the LA, it subsequently returns back to the LV during diastole. Pulse-wave Doppler at the tips of the mitral valve producing a
RI PT
Doppler “E” wave velocity greater than 1.2m/s is consistent with severe regurgitation.27 Systolic flow reversal in any of the pulmonary veins is also associated with severe mitral regurgitation.14
SC
Left ventricular Dimensional Analysis
Structural measurement of the LV and mitral valve is essential in the assessment of FMR.
M AN U
Predictors of poor outcome following restrictive mitral valve annuloplasty include indicators of severe LV remodeling and resultant severe tenting of the mitral apparatus. Findings of LV end diastolic diameter >65mm, LV end systolic diameter >51mm, inter-papillary muscle distance >20mm, tenting area (area between the mitral valve annulus and the leaflets at the beginning of systole) >2.5cm2 (Figure 3), and tenting height (the distance between the mitral plane and the
TE D
point of leaflet coaptation during systole) >10mm (Figure 2) are all associated with recurrent FMR after annuloplasty.14,28_ENREF_31
EP
Tissue Doppler Imaging and Strain Imaging
TDI and strain imaging have been used to demonstrate ventricular and papillary muscle
AC C
dyssynchrony in FMR and subsequent improvement in ERO and RV with CRT therapy.29 Studies using TDI have also shown resting and dynamic ventricular dyssynchrony to be strongly predictive of worsening of FMR with exercise.30,31 Though TDI and strain imaging are not required for FMR diagnosis they may help unmask exercise related symptoms as well as determine response to therapy.
ACCEPTED MANUSCRIPT
Exercise Echocardiography Exercise physiology may alter ventricular loading conditions, geometry and dyssynchrony
RI PT
resulting in worsening of FMR. As such, exercise echocardiography may unmask severe FMR and help to explain patient symptoms.31-34 Worsening FMR with exercise has been found to be an independent predictor of exercise intolerance and lower exercise capacity. In a recent study by
SC
Izumo et al, 30 patients with heart failure underwent symptom limited bicycle stress 2D and 3D echocardiography and cardiopulmonary testing. The 10 patients with increases in ERO of
M AN U
>0.13cm2 were classified as exercised induced FMR and shown to have a significant elevation in pulmonary artery pressures and lower peak oxygen uptake with exercise then patients without exercise FMR. On multivariate analysis ERO was found to be the strongest predictor of peak oxygen uptake.32 Along with reductions in cardiopulmonary testing markers, stress echocardiography has also demonstrated reductions in stroke volume as FMR increases with
TE D
exercise. Such findings may help to explain exercise limitations in patients with FMR.35 In a study by Lancellotti et al, 161 patients with chronic FMR were followed for a mean of 35 months. An ERO difference between exercise and rest >0.13cm2 was associated with increased
EP
mortality compared to those who had an ERO difference 30%
RI PT
undergoing coronary artery bypass grafting (CABG), the surgical treatment of severe FMR (ERO>0.2 cm2) is indicated (Class I, Level of Evidence: C), and should be considered in patients with moderate FMR (ERO>0.1-0.19 cm2, Class IIa, Level of Evidence: C).46 Additionally,
SC
patients with severe FMR, an ejection fraction 0.2 cm2, RV 30-59 mL/beat, and VC 0.30-0.69 cm) and an ejection
TE D
fraction >30%. Seventy-three patients were randomly assigned to CABG or CABG plus restrictive annuloplasty using a complete ring.
Despite greater perioperative morbidity, the
primary end point of peak oxygen consumption at 1-year was significantly better in the CABG
EP
plus mitral valve repair group. Additionally, these patients exhibited LV reverse remodeling, lower B-type natriuretic peptide levels and NYHA functional class scores. Moderate or greater
AC C
FMR was observed at 1-year in 4% of patients in the CABG plus annuloplasty group compared to 50% in the CABG only group.52 Deja et al53 completed a retrospective propensity matched analysis of patients recruited into the STICH trial with moderate to severe FMR and an ejection fraction 30% who remain symptomatic despite optimal medical therapy and have low surgical risk (Class IIb, Level of Evidence: C).46 Isolated mitral valve surgery in patients with an ejection fraction 0.2 cm2
Effective regurgitant orifice (ERO)
> 30 ml
RI PT
Regurgitant volume
> 1.2 m/s
"E" wave velocity
> 40% of left atrium
Regurgitant colour flow jet
> 7 mm
AC C
EP
TE D
M AN U
SC
Vena contracta
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0828-282X(13)01683-8
DOI:
10.1016/j.cjca.2013.11.022
Reference:
CJCA 1048
To appear in:
Canadian Journal of Cardiology
Received Date: 5 June 2013 Revised Date:
21 November 2013
Accepted Date: 21 November 2013
Please cite this article as: Ducas RA, White CW, Wassef AW, Farag A, Bhagirath KM, Freed DH, Tam JW, Functional Mitral Regurgitation: Current Understanding And Approach To Management, Canadian Journal of Cardiology (2013), doi: 10.1016/j.cjca.2013.11.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
FUNCTIONAL
MITRAL
REGURGITATION:
CURRENT
UNDERSTANDING
RI PT
APPROACH TO MANAGEMENT
Authors: Robin A. Ducas, MD. University of Manitoba Christopher W. White, MD. University of Manitoba
Ashraf Farag, MD. University of Manitoba
Darren H. Freed, MD. University of Manitoba James W. Tam, MD. University of Manitoba’
Dr. Robin A. Ducas
TE D
Corresponding Author:
M AN U
Kapil M. Bhagirath, MD. University of British Columbia
SC
Anthony W. Wassef, MD. University of Manitoba
Room Y3021 Bergen Cardiac Care Centre St. Boniface General Hospital 409 Tache Avenue
EP
Winnipeg, Manitoba R2H 2A6
E-mail: [email protected]
AC C
Phone: (204) 258-1290 Fax: (204) 233-9162
Source of Funding: None
AND
ACCEPTED MANUSCRIPT
Brief Summary:
Functional
mitral
regurgitation
(FMR)
frequently
complicates
ischemic
and
non-ischemic
RI PT
cardiomyopathy, and is associated with increased morbidity and mortality. The pathophysiology of FMR is due primarily to ventricular and sub-valvular apparatus dysfunction causing failure of leaflet coaptation. Echocardiography is the primary modality used in diagnosis and allows for assessment of valvular and
approach
incorporating
medical
therapy
and
of
AC C
EP
TE D
M AN U
resynchronization therapies.
consideration
SC
ventricular structure, and interaction. The optimal management of FMR involves an individualized
Page 2
surgical,
percutaneous,
and
ACCEPTED MANUSCRIPT
Abstract: Functional mitral regurgitation (FMR) is a challenging clinical entity that frequently complicates both
RI PT
ischemic and non-ischemic cardiomyopathy. The underlying pathophysiology of FMR is due primarily to ventricular and sub-valvular apparatus dysfunction causing failure of proper leaflet coaptation. Echocardiography is the primary modality used in diagnosis and characterization of FMR. Echocardiography allows for assessment of valvular and ventricular structures as well as their interaction.
SC
FMR portends a poor prognosis, as it is frequently associated with increased morbidity and mortality. The optimal management of FMR involves an individualized approach that incorporates medical therapy and
M AN U
consideration of surgical, percutaneous, and resynchronization therapies according to the severity of regurgitation, presence of symptoms, option for revascularization, and the degree of ventricular
TE D
remodeling.
Key Words:
EP
1. Functional Mitral Regurgitation 2. Ischemic Mitral Regurgitation
AC C
3. Mitral Valve Disease
ACCEPTED MANUSCRIPT
Introduction Mitral regurgitation is the retrograde flow of blood from the left ventricle (LV) to the left atrium
RI PT
(LA) during systole. Normal function of the mitral valve is a complex process and is dependent upon an intact valve annulus, leaflets, chordae tendonae, papillary muscles, and LV wall working in harmony. Perturbations in any of the aforementioned structures may precipitate mitral
SC
regurgitation. One of the earliest classification systems for mitral valve disease is that of Carpentier.1 In this classification scheme mitral valve regurgitation can be separated into three
M AN U
types: type I (coaptation of the leaflets at the annular plane) due to annular dilatation or leaflet perforation; type II (coaptation beyond the annular plane) secondary to leaflet prolapse or papillary muscle rupture; or type III (coaptation proximal to annular plane) associated with valvular and sub-valvular sclerosis with restricted leaflet motion during diastole and systole (IIIa)
TE D
or restricted leaflet motion predominantly during systole (IIIb) (Figure 1).
Functional mitral regurgitation (FMR) refers to mitral regurgitation that is primarily due to a pathologically dilated LV and mitral annulus or to regional disruptions of the LV and sub-
EP
valvular apparatus. FMR is also referred to as “secondary mitral regurgitation” owing to the fact that it is secondary to myocardial pathology and not a primary disease of the valvular tissues.2
AC C
With respect to the Carpentier classification system, FMR corresponds with the class I or IIIb types. In the literature, “ischemic mitral regurgitation” is a term that is widely used and refers to mitral regurgitation resulting from LV dysfunction due to previous ischemic insults. This is a confusing term as valvular dysfunction is the result of prior infarction and impaired myocardial function, not active or transient ischemia of the papillary muscles.2,3
Page 4
ACCEPTED MANUSCRIPT
Epidemiology As distortion of LV geometry and function are key components in FMR, it is not surprising that
RI PT
FMR is common in both ischemic and non-ischemic cardiomyopathy. The prevalence of moderate to severe FMR has been reported to be up to 60% in ischemic cardiomyopathy and in 40% of cases of non-ischemic cardiomyopathy.4,5 Interestingly, FMR is now the leading cause of
SC
mitral regurgitation in the United States.5
M AN U
FMR is an independent risk factor for death and admission to hospital. When using the proximal iso-volumetric surface area (PISA) method for calculating regurgitant volume (RV) and effective regurgitant orifice (ERO) on echocardiography, there is a clear biological gradient; higher regurgitation results in lower survival. Specifically, patients with FMR and an ERO >0.2cm2 have
TE D
been shown to have higher mortality.6
Pathophysiology
EP
Traditionally FMR has been described as a structurally normal mitral valve with impaired function due to ventricular dilation and dysfunction. However, new insights in to myocardial
AC C
adaptation have also demonstrated abnormalities in the mitral leaflets. Indeed FMR is not simply a disease of ventricular dysfunction and may be better understood in terms of ventricular, subvalvular and valvular interaction and adaptation. 7-9
Left Ventricle
ACCEPTED MANUSCRIPT
In mitral regurgitation, during isovolemic ventricular contraction blood is ejected through the mitral valve into the LA due to a lower pressure gradient, resulting in decreased ventricular
RI PT
volume at the end of isovolemic contraction.2 In severe cases, up to 50% of the LV end diastolic volume is ejected into the LA prior to the opening of the aortic valve.10 Initially this may be well tolerated as the LA enlarges. However, eventually LA compliance is exceeded, resulting in
SC
increased LA pressure and progressive development of pulmonary hypertension.11 A vicious cycle then develops, as the regurgitated blood in the LA returns to the LV during diastole,
M AN U
resulting in LV volume overload and progressive dilatation. With increasing ventricular dilatation there is increased wall stress and worsening of myocardial function, leading in turn to worsening mitral regurgitation.12 Dilation and dysfunction of the LV chamber has long been considered a key component of FMR. Chamber dilation translates into mitral annular dilation, displacement of the papillary muscles, and resultant perturbations in valve leaflet closure. Ventricular
TE D
dyssynchrony also may play a part in FMR by further impairing sub-valvular function.
Ventricular and annular dilatation
EP
The mitral valve annulus, composed of both muscular and fibrous tissue, is a structural component of the LV. A normal mitral valve has a three-dimensional (3D) saddle shape that
AC C
undergoes dynamic changes in area throughout the cardiac cycle, facilitating LV filling and valve closure.13 With dilatation of the LV cavity there is concomitant enlargement and distortion of the mitral annular shape, resulting in a more circular annular configuration. This distortion of the mitral valve shape causes mal-coaptation of the anterior and posterior leaflets and results in valvular incompetence.10,14 Further to the structural abnormalities of the mitral annulus with ventricular dilation, Yiu et al, have demonstrated that loss of systolic annular contraction is
ACCEPTED MANUSCRIPT
associated with a larger ERO and a greater degree of regurgitation.8 Thus both appropriate annular size and configuration, in addition to systolic function are important components valvular
RI PT
competence.
Myocardial function and dyssynchrony
SC
Dyssynchrony of the LV myocardium is proposed to result in dyssynchrony of adjacent papillary muscles, disturbing mitral leaflet closure timing and resulting in FMR. Using tissue Doppler
M AN U
imaging (TDI) in 35 patients with impaired ejection fraction (7mm).26 Both of these methods provide simple assessments of FMR severity; however, these methods are prone to over and underestimation and should be combined with
TE D
quantitative methods.
Quantitative Evaluation of Regurgitation
Classically, severe mitral regurgitation is associated with an ERO >0.4cm2 and RV >60mL.26
EP
However, in FMR, lower values for ERO have been associated with worse outcomes. For example, RV of >30mL and an ERO >0.2cm2, (both classically used to define moderate
AC C
regurgitation), have been associated with a severe reduction in life expectancy at 5 years.6 Though not widely adopted, these findings have lead the European Association of Echocardiography to recommended that these lower values (ERO >0.2cm2, and RV >30mL) be used to define severe FMR (Table 1).14
Mitral Inflow Doppler
ACCEPTED MANUSCRIPT
When a large volume of ventricular blood is regurgitated into the LA, it subsequently returns back to the LV during diastole. Pulse-wave Doppler at the tips of the mitral valve producing a
RI PT
Doppler “E” wave velocity greater than 1.2m/s is consistent with severe regurgitation.27 Systolic flow reversal in any of the pulmonary veins is also associated with severe mitral regurgitation.14
SC
Left ventricular Dimensional Analysis
Structural measurement of the LV and mitral valve is essential in the assessment of FMR.
M AN U
Predictors of poor outcome following restrictive mitral valve annuloplasty include indicators of severe LV remodeling and resultant severe tenting of the mitral apparatus. Findings of LV end diastolic diameter >65mm, LV end systolic diameter >51mm, inter-papillary muscle distance >20mm, tenting area (area between the mitral valve annulus and the leaflets at the beginning of systole) >2.5cm2 (Figure 3), and tenting height (the distance between the mitral plane and the
TE D
point of leaflet coaptation during systole) >10mm (Figure 2) are all associated with recurrent FMR after annuloplasty.14,28_ENREF_31
EP
Tissue Doppler Imaging and Strain Imaging
TDI and strain imaging have been used to demonstrate ventricular and papillary muscle
AC C
dyssynchrony in FMR and subsequent improvement in ERO and RV with CRT therapy.29 Studies using TDI have also shown resting and dynamic ventricular dyssynchrony to be strongly predictive of worsening of FMR with exercise.30,31 Though TDI and strain imaging are not required for FMR diagnosis they may help unmask exercise related symptoms as well as determine response to therapy.
ACCEPTED MANUSCRIPT
Exercise Echocardiography Exercise physiology may alter ventricular loading conditions, geometry and dyssynchrony
RI PT
resulting in worsening of FMR. As such, exercise echocardiography may unmask severe FMR and help to explain patient symptoms.31-34 Worsening FMR with exercise has been found to be an independent predictor of exercise intolerance and lower exercise capacity. In a recent study by
SC
Izumo et al, 30 patients with heart failure underwent symptom limited bicycle stress 2D and 3D echocardiography and cardiopulmonary testing. The 10 patients with increases in ERO of
M AN U
>0.13cm2 were classified as exercised induced FMR and shown to have a significant elevation in pulmonary artery pressures and lower peak oxygen uptake with exercise then patients without exercise FMR. On multivariate analysis ERO was found to be the strongest predictor of peak oxygen uptake.32 Along with reductions in cardiopulmonary testing markers, stress echocardiography has also demonstrated reductions in stroke volume as FMR increases with
TE D
exercise. Such findings may help to explain exercise limitations in patients with FMR.35 In a study by Lancellotti et al, 161 patients with chronic FMR were followed for a mean of 35 months. An ERO difference between exercise and rest >0.13cm2 was associated with increased
EP
mortality compared to those who had an ERO difference 30%
RI PT
undergoing coronary artery bypass grafting (CABG), the surgical treatment of severe FMR (ERO>0.2 cm2) is indicated (Class I, Level of Evidence: C), and should be considered in patients with moderate FMR (ERO>0.1-0.19 cm2, Class IIa, Level of Evidence: C).46 Additionally,
SC
patients with severe FMR, an ejection fraction 0.2 cm2, RV 30-59 mL/beat, and VC 0.30-0.69 cm) and an ejection
TE D
fraction >30%. Seventy-three patients were randomly assigned to CABG or CABG plus restrictive annuloplasty using a complete ring.
Despite greater perioperative morbidity, the
primary end point of peak oxygen consumption at 1-year was significantly better in the CABG
EP
plus mitral valve repair group. Additionally, these patients exhibited LV reverse remodeling, lower B-type natriuretic peptide levels and NYHA functional class scores. Moderate or greater
AC C
FMR was observed at 1-year in 4% of patients in the CABG plus annuloplasty group compared to 50% in the CABG only group.52 Deja et al53 completed a retrospective propensity matched analysis of patients recruited into the STICH trial with moderate to severe FMR and an ejection fraction 30% who remain symptomatic despite optimal medical therapy and have low surgical risk (Class IIb, Level of Evidence: C).46 Isolated mitral valve surgery in patients with an ejection fraction 0.2 cm2
Effective regurgitant orifice (ERO)
> 30 ml
RI PT
Regurgitant volume
> 1.2 m/s
"E" wave velocity
> 40% of left atrium
Regurgitant colour flow jet
> 7 mm
AC C
EP
TE D
M AN U
SC
Vena contracta
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
