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EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
EXPERT CONSENSUS DECISION PATHWAY
2017 ACC Expert Consensus Decision Pathway on the Management of Mitral
Regurgitation
A Report of the American College of Cardiology Task Force on Expert Consensus Decision
Pathways
WRITING COMMITTEE
Patrick T. O'Gara, MD, MACC, Chair
Paul A. Grayburn, MD, FACC, Vice-Chair
Vinay Badhwar, MD, FACC, Vice-Chair
Luis C. Afonso, MBBS, FACC
John D. Carroll, MD, FACC
Sammy Elmariah, MD, FACC
Aaron P. Kithcart, MD
Rick A. Nishimura, MD, MACC
Thomas Ryan, MD, FACC
Allan Schwartz, MD, FACC
Lynne Warner Stevenson, MD, FACC
TASK FORCE ON EXPERT CONSENSUS DECISION PATHWAYS
James L. Januzzi Jr., MD, FACC, Chair
Luis C. Afonso, MBBS, FACC
Joseph E. Marine, MD, FACC
Brendan Everett, MD, FACC
Pamela B. Morris, MD, FACC
Adrian F. Hernandez, MD, FACC
Robert N. Piana, MD, FACC
William Hucker, MD, PhD
Karol E. Watson, MD, FACC
Hani Jneid, MD, FACC
Barbara S. Wiggins, PharmD, AACC
Dharam J. Kumbhani, MD, SM,
FACC
This document was approved by the American College of Cardiology Clinical Policy Approval
Committee on behalf of the Board of Trustees in [insert month] 2017.
The American College of Cardiology requests that this document be cited as follows: O’Gara
PT, Grayburn PA, Badhwar V, Afonso LC, Carroll JD, Elmariah S, Kithcart AP, Nishimura RA,
Ryan T, Schwartz A, Stevenson LW. 2017 ACC Expert Consensus Decision Pathway on the
Management of Mitral Regurgitation. J Am Coll Cardiol 2017; XX:XXX-XX.
Copies: This document is available on the World Wide Web site of the American College of
Cardiology (www.acc.org). For copies of this document, please contact Elsevier Inc. Reprint
Department, fax (212) 633-3820, e-mail [email protected].
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EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
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Cardiology. Please contact Elsevier’s permission department [email protected]
© 2017 by the American College of Cardiology Foundation
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EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
TABLE OF CONTENTS
PREFACE ....................................................................................................................................... 5
1. ABSTRACT ............................................................................................................................... 7
2. INTRODUCTION ...................................................................................................................... 8
3. METHODS ................................................................................................................................. 9
4. ASSUMPTIONS AND DEFINITIONS ................................................................................... 10
5. CENTRAL ILLUSTRATION .................................................................................................. 11
Figure 1. Pathway for Management of MR ............................................................................... 11
6. DESCRIPTION AND RATIONALE ........................................................................................ 12
6.1. Evaluation of the Patient .................................................................................................... 13
6.2. Hemodynamic Effects of MR............................................................................................. 15
6.3. Determining Mechanism and Etiology of MR ................................................................... 16
Figure 2. Decision Tree for Distinguishing Primary from Secondary MR ........................... 16
Table 1. Suggested Qualitative and Quantitative Parameters for Standardized Echo
Reporting ............................................................................................................................... 19
Figure 3. Anterior Leaflet Override in Functional MR ......................................................... 21
6.3.1. Spectrum of Functional MR ........................................................................................ 21
6.4. Assessment of MR Severity ............................................................................................... 22
6.4.1 Color Flow Doppler (CFD) Jet Size ............................................................................. 22
Figure 4. Effect of Driving Velocity on Size and Penetration of Color Doppler MR Jet ..... 23
6.4.2. Quantitative Parameters............................................................................................... 24
Figure 5. MR Limited to Late Systole in Mitral Valve Prolapse.......................................... 25
Figure 6. Example of Underestimation of EROA by 2D PISA in a Patient with Secondary
MR and a Markedly Crescentic Orifice Shape ...................................................................... 26
6.4.3. Integration of Multiple Parameters .............................................................................. 27
Figure 7. Decision Tree for Assessing Severity of MR by TTE .......................................... 27
Table 2. Strengths and Limitations of Common Echocardiographic Parameters of MR
Severity.................................................................................................................................. 29
Figure 8. Clinical Algorithm for the Management of MR based on TTE ............................. 32
6.4.4 Dynamic Nature of MR ................................................................................................ 33
6.4.5 Differences in Assessing MR Severity in Primary vs. Secondary MR ........................ 34
6.4.6 Prognosis in MR ........................................................................................................... 35
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6.5. Treatment of Chronic Mitral Regurgitation........................................................................ 36
6.5.1. Surgical Treatment of Mitral Regurgitation ................................................................ 37
6.5.2. Feasibility of Surgical Repair ...................................................................................... 39
Figure 9. Decision Tree for Determining Surgical Mitral Valve Repair vs. Replacement in
Patients with Severe MR ....................................................................................................... 39
Table 4: Pathoanatomically Directed Contemporary Surgical Techniques for Mitral
Regurgitation ......................................................................................................................... 42
Table 5. Feasibility of Transcatheter Edge-to-Edge Clip Repair .......................................... 43
Figure 10. Examples of Valve Morphology that is Amenable to Surgical Repair in Patients
with Primary MR ................................................................................................................... 44
6.5.3. Determination of Risk for Surgery .............................................................................. 44
6.5.4. Transcatheter Treatment of Mitral Regurgitation ........................................................ 45
6.5.5. Edge-to-Edge Leaflet Coaptation ................................................................................ 46
Figure 11. Transcatheter Edge-to-Edge Mitral Valve Clip .................................................. 47
Figure 12. Algorithm for Determining Eligibility for Transcatheter Edge-to-Edge Mitral
Valve Clip.............................................................................................................................. 48
6.5.6. Feasibility of Edge-to-Edge Leaflet Coaptation .......................................................... 48
Figure 13. Transcatheter Edge-to-Edge Mitral Valve Clip .................................................. 49
7. DISCUSSION AND IMPLICATION OF PATHWAY ........................................................... 49
PRESIDENTS AND STAFF......................................................................................................... 52
APPENDIX 1: Author Relationships With Industry and Other Entities (Relevant) ..................... 53
APPENDIX 2: Peer Reviewer Relevant RWI ............................................................................... 57
APPENDIX 3: Abbreviations........................................................................................................ 58
References ..................................................................................................................................... 59
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PREFACE
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The American College of Cardiology (ACC) develops a number of clinical policy
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documents to provide members with guidance on clinical topics. While clinical practice
4
guidelines remain the primary mechanism for offering evidence based recommendations,
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such guidelines may contain gaps in how to make clinical decisions, particularly when
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equipoise is present in a topic. Expert Consensus Documents are intended to provide
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guidance for clinicians in areas where evidence may be limited, new and evolving, or
8
lack sufficient data to fully inform clinical decision making.
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In an effort to increase the impact of ACC clinical policy on patient care, an ACC
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Presidential Task Force was formed in 2014 to examine processes of ACC’s clinical
11
documents. The main recommendation of the Task Force was a new focus on concise
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decision pathways and/or key points of care, instead of the traditional longer documents.
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The Task Force also established criteria for identifying high-value clinical topics to be
14
addressed, as well as an innovative approach to collecting stakeholder input through a
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roundtable or think tank meeting. To complement the new focus on brief decision
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pathways and key points, Expert Consensus Documents were rebranded Expert
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Consensus Decision Pathways (ECDPs).
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While Decision Pathways have a new format, they maintain the same goal of
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Expert Consensus Documents to develop clinical policy based on expert opinion in areas
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which important clinical decisions are not adequately addressed by the available existing
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trials. ECDPs are designed to complement the guidelines and bridge the gaps in clinical
22
guidance that remain. In some cases, topics covered by ECDPs will be addressed
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subsequently by ACC/AHA guidelines as the evidence base evolves. The writing
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committees are charged with developing algorithms that are more actionable and can be
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implemented into tools or apps to accelerate the use of these documents at point of care.
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Decision Pathways are not intended to provide a single correct answer, but to encourage
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clinicians to ask certain questions and consider important factors as they come to their
5
own decision on a treatment plan for their patients. There may be multiple pathways that
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can be taken for treatment decisions and the goal is to help clinicians make a more
7
informed decision.
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James L. Januzzi, MD, FACC
Chair, ACC Task Force on Expert Consensus Decision Pathways
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1. ABSTRACT
2
Mitral regurgitation is a complex valve lesion that can pose significant management
3
challenges for the cardiovascular clinician. Recognition should prompt an assessment of
4
its etiology, mechanism, severity, and indications for treatment. A structured approach to
5
evaluation based on clinical findings, precise echocardiographic imaging and adjunctive
6
testing when necessary should help clarify decision making. Treatment goals include
7
timely intervention by an experienced heart team to prevent left ventricular dysfunction,
8
heart failure, reduced quality of life and premature death.
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2. INTRODUCTION
2
Improvements in multi-modality imaging, surgical outcomes and the advent of
3
transcatheter techniques have transformed the approach to patients with valvular heart
4
disease. Long-term natural history studies have informed clinical decision-making
5
regarding the appropriate timing for valve intervention. Nevertheless, knowledge and
6
performance gaps remain that may adversely affect patient outcomes and for which
7
practice tools may provide a means for improvement.
8
Recent emphasis has been placed on the heart valve team approach to patients
9
with calcific aortic stenosis, in large measure due to improvements in transcatheter and
10
surgical therapies. The evaluation and management of patients with mitral regurgitation
11
(MR), a highly prevalent valve lesion among aging U.S. adults, is more complex, in part
12
related to its varying etiologies, dynamic nature and the intricate interplay among the
13
functional components of the mitral apparatus, including the left ventricle, papillary
14
muscles, chordae tendineae, leaflets and annulus.
15
This manuscript contains clinical expert consensus recommendations to guide the
16
approach to patients identified with MR with emphasis on clinical and echocardiographic
17
assessment, establishment of etiology and mechanism, consideration of associated
18
hemodynamic consequences, recognition of the triggers for surgical referral, appreciation
19
of the graded complexity of mitral valve repair as a function of pathoanatomy, and
20
understanding the limited role for transcatheter mitral valve repair in the United States at
21
the current time. Recommendations are based on the AHA/ACC 2014 Guideline for the
22
Management of Patients with Valvular Heart Disease (1), but augmented with additional
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clinical context and practical tips for medical and surgical decision-making in complex
2
patient scenarios.
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3. METHODS
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The writing committee was assembled in September 2015. In addition to the master
5
document, figures and tables contained herein, the writing committee developed a
6
template for structured echocardiographic reporting of MR etiology, mechanism,
7
Carpentier (functional) classification, severity and associated findings, as well as a
8
checklist for use when contemplating referral of patients for advanced imaging or
9
surgical/interventional therapy. The manuscript and tools were based on the writing
10
committee’s knowledge of the evidence assembled and recommendations made in the
11
AHA/ACC 2014 Guideline for Management of Patients with Valvular Heart Disease (1),
12
additional literature review through July 2016, and expert consensus when evidence was
13
lacking or limited. The writing committee included representatives from the following
14
areas: general cardiology, heart valve disease, heart failure, imaging,
15
interventional/structural heart disease, valve surgery, fellows-in-training and early career
16
professionals.
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The work of the writing committee was supported exclusively by the ACC
18
without commercial support. Writing committee members volunteered their time to this
19
effort. Conference calls of the writing committee were confidential and attended only by
20
committee members and ACC staff. A formal peer review process was completed
21
consistent with ACC policy and included expert reviewers nominated by the ACC (see
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Appendix 2). A public comment period was also held to obtain further feedback.
23
Following reconciliation of all comments, this document was approved for publication by
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the ACC Clinical Policy Approval Committee on behalf of the Board of Trustees and
2
endorsed by xx.
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4. ASSUMPTIONS AND DEFINITIONS
4
This effort was neither conceived nor designed to rewrite or re-interpret the AHA/ACC
5
2014 Guidelines for the Management of Patients with Valvular Heart Disease (1).The
6
writing committee did not stipulate the means by which mitral regurgitation may first be
7
appreciated and did not focus on community efforts to increase its rate of accurate
8
detection. Evaluation and management algorithms in this document flow from an
9
echocardiographically validated diagnosis of mitral regurgitation. Primary MR is defined
10
by principal involvement of the leaflets and/or chordae tendineae in the pathologic
11
process (e.g., myxomatous disease, endocarditis); secondary (functional) MR is
12
characterized by incompetence due to adverse changes in left ventricular size, shape or
13
function with or without annular dilatation (e.g., ischemic cardiomyopathy); mixed MR is
14
due to both primary and secondary causes (e.g., mitral valve prolapse/flail with ischemic
15
cardiomyopathy). The writing committee used the American Society of
16
Echocardiography guidelines to grade mitral regurgitation severity and emphasized the
17
need for additional testing when severity could not be established with certainty (2). The
18
writing committee acknowledged previous publications regarding institutional and
19
operator requirements for programs of transcatheter heart valve intervention (3). The
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writing committee did not define a comprehensive valve center nor stipulate the criteria
21
by which a mitral valve surgeon is considered experienced or highly experienced. These
22
latter two issues are of intense interest to the community and the focus of current
23
deliberation and multi-societal collaboration.
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5. CENTRAL ILLUSTRATION
2
Figure 1. Pathway for Management of MR
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6. DESCRIPTION AND RATIONALE
2
Mitral regurgitation (MR) is the most common type of moderate or severe heart valve
3
disease among U.S. adults older than 55 years and its prevalence increases further as a
4
function of age (4). It can result from pathological abnormalities of the mitral valve
5
leaflets or chordae (primary MR) or when leaflet coaptation is reduced by
6
dilation/dysfunction of the left ventricle (LV) or left atrium (LA) (secondary or functional
7
MR). It is now recognized that primary and secondary MR are different diseases with
8
different prognostic implications and indications for treatment. The 2014 AHA/ACC
9
Guideline for the Management of Patients with Valvular Heart Disease (1) emphasizes
10
disease staging, wherein patients are classified as being at risk for developing MR (Stage
11
A), having mild or moderate MR which may progress over time (Stage B), asymptomatic
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severe MR (Stage C) with normal (C1) or reduced (C2) LV function or symptomatic
13
severe MR (Stage D). Indications for treatment are dependent on disease stage,
14
characterization of which relies on accurate assessment of MR severity, as well as an
15
understanding of the efficacy and safety of therapy. A recent survey commissioned by
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the ACC identified multiple knowledge and practice gaps among respondents, including
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failure to identify clinically significant MR on physical examination, failure to recognize
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the difference between primary and secondary MR, poor quality and incomplete
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echocardiographic assessment and reporting, lack of awareness of guideline-based
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recommendations for treatment, and lack of awareness of the volume and quality of
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surgical repair at their institution (3). This consensus document focuses on the evaluation
22
and management of patients with MR with specific emphasis on 1) clinical assessment, 2)
23
proper identification of the mechanism and etiology of MR, 3) determination of MR
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severity, 4) assessment of the feasibility of surgical or transcatheter repair, and 5)
2
indications for possible referral to a regional, comprehensive valve center. Within each
3
section, clear and precise terminology is recommended for communicating the essential
4
features of MR in the medical record. Because acute MR typically presents with
5
hemodynamic compromise for which the need for urgent intervention is well recognized,
6
this document focuses on chronic MR, where the current gaps in knowledge and practice
7
are more common.
8
6.1. Evaluation of the Patient
9
10
Assessment of the patient with chronic MR begins with a careful history and physical
11
examination. Symptoms may be absent or subtle, even in patients with severe MR due to
12
flail leaflet (Stage C) (5). The lack of symptoms in the chronic phase may relate to
13
enhanced LA compliance whereby the regurgitant volume (RVol) can be accommodated
14
within an enlarging LA without an increase in pressure sufficient to cause dyspnea.
15
Patients may also reduce their activity level to avoid symptoms, often subconsciously. It
16
is helpful to ask the patient what is the most vigorous activity s/he currently undertakes
17
and compare that to what s/he was able to do previously. Family members may often
18
report symptoms and/or diminished activity about which the patient is unaware. Another
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simple question to ask is what s/he is capable of doing on a scale of 1-10, with 1 being no
20
activity at all and 10 being any activity without limitation (6). Common symptoms in
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addition to exertional dyspnea include fatigue and palpitations. Incorporating a
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standardized and validated patient questionnaire on health status into the medical record,
23
specifically the Kansas City Cardiomyopathy Questionnaire, is encouraged. This tool
24
provides insight into the patient’s perception of their functional state and quality of life
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and is now routinely used before and after transcatheter therapy and entered into the
2
STS/ACC Transcatheter Valve Therapy (TVT) Registry.
3
If the patient is asymptomatic, exercise testing may be performed safely and may
4
elicit symptoms or demonstrate reduced exercise capacity. If done with
5
echocardiographic imaging exercise testing may show elevated PA systolic pressures,
6
worsening MR, or failure of LV or RV systolic function to augment normally (7-9).
7
Thus, exercise testing often results in reclassification of patients from Stage C to D or
8
even from Stage B to D. The 6 minute walk test is a simple, inexpensive, and
9
reproducible submaximal exercise tool to assess functional capacity. It may reflect
10
normal daily activity level better than maximal, symptom-limited exercise tests in fragile
11
or elderly patients.
12
In patients with primary MR, the presence of a diastolic filling complex (S3 plus
13
short diastolic murmur) suggests a significant RVol and severe MR. In secondary MR, an
14
S3 gallop is harder to interpret because it may be due to the underlying LV dysfunction.
15
If the murmur of primary MR is not audible after listening in multiple positions or with
16
dynamic maneuvers, or limited in timing to late systole only, it is likely that the
17
regurgitation is not severe. One or more non-ejection clicks may be audible. Differential
18
radiation of the murmur of primary MR provides a clue as to the underlying leaflet
19
pathology. Murmurs associated with anterior leaflet flail are directed to the axilla and left
20
infrascapular area, whereas murmurs with posterior leaflet flail radiate anteriorly and can
21
be confused with systolic ejection murmurs. With functional MR, the murmur is usually
22
best heard at the apex and radiates to the axilla. Atrial fibrillation (AF) or other
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arrhythmias may be present in patients with MR and can make the examination more
2
challenging, particularly when the heart rate is rapid.
3
6.2. Hemodynamic Effects of MR
4
5
The hemodynamic effects of chronic severe primary MR are well known. Chronic MR
6
imposes a pure volume overload on the LV, resulting in eccentric hypertrophy and LV
7
dilation. Increased preload combined with low to normal afterload augments LVEF,
8
which is typically supranormal. As the LV dilates, LV wall stress increases. Incipient and
9
irreversible myocardial dysfunction may occur due to the longstanding LV volume
10
overload. Because the ejection fraction is a load dependent measure of LV function, it
11
can be preserved even when myocardial contractile function becomes abnormal. Thus,
12
current practice guidelines recommend intervention in primary MR before the LVEF falls
13
to or below 60% or the end-systolic dimension reaches or exceeds 4.0 cm (1). In
14
secondary MR, the relationship between LVEF and the associated volume overload is
15
confounded by the fact that LV dilation and decreased function are the cause rather than
16
the consequence of MR. However, the presence of any degree of secondary MR is
17
associated with worsened prognosis in both ischemic and nonischemic cardiomyopathies
18
(10-17). To date, no therapy, including valve repair or replacement, has been shown to
19
improve survival in patients with severe functional MR.
20
In addition to its effects on LV size, chronic severe MR results in LA dilation,
21
increased LA pressure and pulmonary venous hypertension. Accordingly, atrial
22
fibrillation is common in chronic severe MR. Persistent or long-standing persistent AF
23
may also cause or worsen MR due to the associated dilation of the LA and mitral
24
annulus. Therefore, the assessment of MR severity must take into account the
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pathoanatomy of the mitral apparatus, the size and function of the LV, LA size/volume,
2
pulmonary artery pressure and the presence of AF.
3
6.3. Determining Mechanism and Etiology of MR
4
Figure 2. Decision Tree for Distinguishing Primary from Secondary MR
5
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The identification of MR mechanism and etiology is most commonly achieved by
2
transthoracic echocardiography (TTE). Mitral valve morphology should be carefully
3
assessed in multiple views. If image quality is poor with TTE, transesophageal
4
echocardiography (TEE) may often be needed to define anatomy and function more
5
precisely. TEE may identify lesions such as vegetations or flail segments not detected by
6
TTE (18-22). Careful measurement of LV and LA volumes, as well as LV dimensions,
7
should be performed according to ASE guidelines for chamber quantification (23). Mitral
8
valve morphology, LV and LA volumes, and LV size and systolic function are used
9
together to classify the mechanism and etiology of MR (Figure 2). Abnormal mitral
10
leaflet morphology includes thickening, calcification, redundancy, perforation,
11
vegetations, other masses, and clefts. Such abnormalities should be described in detail
12
(diffuse vs focal, size, leaflet location). Abnormal subvalvular morphology includes
13
chordal rupture, thickening, fusion, vegetations or masses, which should similarly be
14
described in detail by size and location. Abnormal annular morphology includes dilation
15
and calcification. Mitral annular calcification can be localized posteriorly or extend into
16
the LV outflow tract or LV myocardium. When MR is due to primary mitral valve
17
pathology, left-sided chamber dilation should be considered a clue that the MR is both
18
chronic and severe. On the other hand, primary MR with normal LV and LA size,
19
function, and volume is unlikely to be severe. If the mitral apparatus is structurally
20
normal, significant MR is likely to be secondary. In such cases, the mechanism of MR
21
still needs to be identified. For example, most patients with secondary MR have a dilated
22
LV with global or regional wall motion abnormalities with either systolic tethering of the
23
leaflets, annular dilation, or both (24-29). However, isolated regional wall motion
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abnormalities, particularly in the inferobasal or posterobasal segments may cause severe
2
secondary MR despite preserved LV function and dimensions. It is also possible to have
3
MR secondary to pure annular dilation in patients with severe LA dilation (30). This has
4
been termed “atrial functional MR” and it is mostly commonly seen in persistent or long-
5
standing persistent AF or in restrictive cardiomyopathies, such as that due to amyloid.
6
Once leaflet morphology is characterized, leaflet motion should be described using
7
Carpentier’s classification system (31). Normal leaflet motion (Type I) may be seen in
8
primary MR due to endocarditis, perforation, or clefts and in primary or secondary MR
9
due to isolated annular dilation. Excessive leaflet motion (Type II) is most commonly
10
seen with mitral valve prolapse or flail leaflet. Leaflet prolapse occurs when the leaflet
11
body moves above the saddle-shaped annulus in systole; leaflet flail occurs when a focal
12
portion of the leaflet edge moves above the annulus and zone of coaptation. With flail
13
leaflets, torn chords are usually visible and are associated with adverse prognosis.
14
Restricted leaflet motion (Type III) is sub-classified into restriction during both systole
15
and diastole (IIIA) or during systole only (IIIB). The former is classic for rheumatic
16
mitral valve disease, radiation or drug-induced injury, or other inflammatory conditions.
17
The latter is typical of MR secondary to ischemic or nonischemic cardiomyopathy. It is
18
also important to note that mixed pathology can and does occur. Untreated primary MR
19
eventually results in irreversible LV dilation/dysfunction in which both leaflet prolapse
20
and tethering may coexist. Other examples include patients with long-standing secondary
21
MR due to ischemic heart disease or AF who subsequently rupture a chord, or patients
22
with mitral valve prolapse who have a myocardial infarction or develop a
23
cardiomyopathy. A common mistake in clinical practice is to misconstrue anterior leaflet
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override as prolapse. In Type IIIB leaflet motion, the posterior leaflet is often severely
2
tethered and the anterior leaflet overrides it (Figure 3) but does not move above the
3
annular plane. This finding does not equate with anterior leaflet prolapse, nor mixed
4
etiology MR. MR jet direction by color flow Doppler (CFD) provides an important clue
5
to the mechanism of MR. An anteriorly directed jet is most commonly due to posterior
6
leaflet prolapse/flail or anterior leaflet restriction, whereas a posteriorly directed jet is
7
typically due to anterior leaflet prolapse/flail or posterior leaflet restriction. If the jet
8
direction is eccentric, but the mechanism uncertain, TEE is indicated to clarify leaflet
9
pathology and motion. Table 1 lists the descriptors of MR mechanism and severity that
10
should be included in standardized echocardiographic reports.
11
12
13
Table 1. Suggested Qualitative and Quantitative Parameters for Standardized Echo
Reporting
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Figure 3. Anterior Leaflet Override in Functional MR
LV
PML
AML
LA
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5
6
7
8
9
10
11
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Figure 3. Anterior leaflet override in secondary MR due to ischemic cardiomyopathy. Apical
long-axis views showing fixed posterior mitral leaflet (PML, blue arrow) with an overriding
anterior mitral leaflet (AML, yellow arrow). Coaptation is absent with a large “wrap-around”
color Doppler jet directed posteriorly by the fixed PML (right panel). This is commonly
misdiagnosed as mitral valve prolapse, but cannot be such because the AML never moves
superiorly to the mitral annulus (dotted line). LV = left ventricle; LA = left atrium.
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6.3.1. Spectrum of Functional MR
Functional MR occurs along a spectrum of severity of LV dysfunction. At one end of the
15
spectrum is a severely dilated, spherical LV with markedly depressed LV systolic
16
function and functional MR. Treatment of MR may not improve symptoms, quality of
17
life, or result in reverse LV remodeling because the primary problem is severe LV
18
dysfunction. Heart transplant or destination LV assist device therapy may be more
19
effective treatment strategies than mitral valve surgery in this context. At the other end
20
of the spectrum, a patient with an isolated inferobasal myocardial infarction may develop
21
severe functional MR due to posterior leaflet tethering, despite normal LV size and
22
ejection fraction. In such patients, the severe MR is the cause of heart failure and surgery
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may be indicated for symptom relief. In the middle of the spectrum, it can be very hard
2
to distinguish whether MR, LV dysfunction, or both are contributing to heart failure
3
symptoms.
4
6.4. Assessment of MR Severity
5
6
6.4.1 Color Flow Doppler (CFD) Jet Size
Severity of MR is most commonly assessed using CFD during TTE or TEE. CFD is a
7
misnomer because it is not actually a flow image. It is an image of the spatial distribution
8
of velocities within the image plane, and is profoundly affected by instrument settings
9
and hemodynamic factors (2). If these are held constant, the size of a jet through a given
10
effective regurgitant orifice area (EROA) is determined by its momentum flux, ρ AV2,
11
where ρ is blood density, A is orifice area and V2 is velocity squared (32). Thus, a 6.0
12
m/s MR jet appears 44% larger than a 5.0 m/s MR jet on CFD. High velocity MR jets,
13
such as occur with hypertension, aortic stenosis or LV outflow tract obstruction, will
14
therefore make MR appear worse on CFD (Figure 4) and this should be recognized by
15
the interpreting physician. Accordingly, it is crucial to record blood pressure, estimated
16
LV systolic pressure in the presence of aortic stenosis or LV outflow obstruction, heart
17
rate, and rhythm at the time of TTE and consider them when grading MR severity (2).
18
The tendency for CFD to overestimate MR severity has recently been shown in a study
19
comparing TTE to cardiac magnetic resonance (CMR) for quantitation (33) and also
20
explains why healthy individuals with no heart murmur often have mild MR on CFD
21
(34). On the other hand, MR can be significantly underestimated when jets have a low
22
driving velocity or are markedly eccentric as momentum is transferred to the LA wall
23
(35). Low velocity jets (i.e. 4 m/s) suggest high LA pressure and low LV pressure and
22
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
therefore indicate severe MR with hemodynamic compromise (assuming proper
2
alignment of the CW Doppler beam with the MR jet). In addition to jet driving velocity
3
and eccentricity, CFD jet size is affected by multiple other technical and hemodynamic
4
factors (36). Thus, both U.S. and European guidelines recommend that MR jet size by
5
CFD not be used alone to assess MR severity (32,37).
6
7
8
Figure 4. Effect of Driving Velocity on Size and Penetration of Color Doppler MR
Jet
9
10
11
12
13
14
15
16
17
18
19
Figure 4. Example of the effect of driving velocity on size and penetration of MR jets. Top
panels. Large MR jet (white arrows) penetrating deep into LA in apical 4- (left) and 2- (right)
chamber views. In both views, the jet origin is narrow with a tiny proximal flow convergence
zone (yellow arrows). Bottom left. CW Doppler of MR jet shows a very high velocity 6.5 m/s,
corresponding to a LV-LA pressure gradient 170 mmHg. In this patient, severe aortic stenosis
was present, leading to a very high LV systolic pressure. Bottom right. PISA confirms mild MR
with EROA 0.10 cm2 and RVol 23 ml.
23
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1
2
3
6.4.2. Quantitative Parameters
Calculation of EROA, a marker of lesion severity, as well as RVol and regurgitant
4
fraction (RF), is strongly recommended by ASE Guidelines for assessing MR severity
5
(2). They can be measured by several techniques including the proximal isovelocity
6
surface area (PISA) method, volumetric methods and 3D imaging. It is crucial to
7
recognize the technical limitations and imprecision of each method and the overlap of
8
values obtained. Volumetric methods (including those with CMR) suffer from
9
multiplication of the errors inherent in measurement of stroke volumes at different
10
locations, but account for the whole of MR over the duration of systole. Single frame
11
measurements, such as with PISA or vena contracta width or area, can markedly
12
overestimate MR severity when the jet is limited to early or late systole (Figure 5) (38).
13
When MR is holosystolic, properly measured values of EROA ≥ 0.4 cm2, RVol ≥ 60 ml
14
or RF ≥50% are highly specific for severe MR. Properly measured values of EROA ≤ 0.2
15
cm2, RVol ≤ 30 ml or RF < 30% are highly specific for mild MR. Intermediate values
16
can occur in severe MR, but lack specificity. An example wherein lower values of
17
EROA and RVol may represent severe MR include markedly crescentic orifice geometry
18
in secondary MR, where PISA yields a falsely low value for EROA due to its inherent
19
assumption of a round orifice (Figure 6) (39-48). Another example is when multiple MR
20
jets are present, such that a measured EROA from a single jet does not reflect the totality
21
of MR severity. Addition of multiple EROA or vena contracta areas should be accurate,
22
but has not been well validated. It is also common to find lower quantitative values in the
23
setting of flail leaflets or with relatively smaller LV volumes (i.e. women). In such cases,
24
there are usually other signs of severe MR.
24
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
3
4
5
6
7
8
9
10
11
Figure 5. MR Limited to Late Systole in Mitral Valve Prolapse
Figure 5. Example of non-holosystolic MR in mitral valve prolapse. Top panels show no MR
by color Doppler in early systole (top left) and mid-systole (top right). Late systolic MR is
present by color Doppler (bottom left) and continuous wave Doppler (bottom right). EROA
calculated as 0.24 cm2 with RVol 17 ml. LA volume, LV size and systolic function and
pulmonary vein flow were normal in this patient with mild MR. However, relying only on the
single frame EROA in this case would overestimate MR severity.
25
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
3
4
5
6
7
8
9
10
11
12
13
Figure 6. Example of Underestimation of EROA by 2D PISA in a Patient with
Secondary MR and a Markedly Crescentic Orifice Shape
Figure 6. Underestimation of EROA and RVol by 2D PISA due to markedly crescentic orifice
shape. Top Panel: TEE Image with 2D PISA EROA 0.25 cm2. Bottom Panel: 3D Reconstruction
of the Vena Contracta Showing Larger Orifice of 0.5 cm2. Left panels show PISA radius (top
left) and CW velocity of MR (bottom left) by TEE. EROA and RVol calculate to values of 0.17
cm2 and 22 ml, respectively. Middle and Right panels show 3D reconstruction of the vena
contracta (bottom middle), which is crescentic in shape with measured area (VCA) 0.52 cm2 and
calculated RVol 67 ml. The PISA values (which assume circular orifice geometry) indicate mild
MR; the 3D VCA severe MR.
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1
6.4.3. Integration of Multiple Parameters
2
3
Figure 7. Decision Tree for Assessing Severity of MR by TTE
4
5
27
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1
A comprehensive approach is recommended whereby multiple parameters are evaluated
2
and integrated to form a final determination of MR severity (2,37). The strengths and
3
limitations of these parameters are listed in Table 2 and have been described in detail in
4
the ASE Guidelines for Assessment of Native Valve Regurgitation (2). Evaluation of MR
5
severity requires a comprehensive TTE study that includes assessment of these
6
parameters. It is important to emphasize that no single echocardiographic parameter has
7
the measurement precision or reproducibility to serve as the sole arbiter of MR severity.
8
Moreover, MR severity is notoriously dynamic (49-51). Therefore, the effects of chronic
9
MR on LV and LA volumes and pulmonary artery pressure must be considered in an
10
integrative fashion. Nevertheless, it is recognized that most physicians interpreting an
11
echocardiogram look at CFD to identify the presence of MR and form an initial
12
impression of its severity. This type of assessment should be considered only a starting
13
point that requires further confirmation using a Bayesian approach that integrates
14
multiple factors to arrive at a final determination (Figure 7). After an initial impression
15
of MR severity is formed, one should next consider whether LA and LV sizes are normal
16
and whether the MR is holosystolic. For example, if one assesses MR as severe based on
17
a large CFD jet, but LA and LV sizes are normal and the MR is limited to late systole, the
18
initial impression is most likely an overestimate. One should consider common reasons
19
for overestimation of MR, such as high MR driving velocity (Figure 4) and MR duration
20
limited to very early or very late systole (Figure 5). When multiple specific parameters
21
for mild or severe MR align with the initial impression of MR severity, MR can be
22
correctly graded with high probability of being accurate. Fortunately, this scenario is
23
relatively common in practice, especially with the finding of mild MR and a structurally
28
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
normal mitral valve. However, when different parameters are discordant among
2
themselves or with the clinical findings, MR severity should be considered uncertain and
3
further testing pursued. In such cases, TEE may be sufficient to define leaflet pathology
4
and quantitate MR severity. CMR is generally more accurate and reproducible for
5
quantitating RVol and RF, as well as LV volumes and LVEF (52-56).
6
7
8
Table 2. Strengths and Limitations of Common Echocardiographic Parameters of
MR Severity
Parameter
Strengths
Weaknesses
Valve Morphology
Flail leaflets or ruptured
papillary muscles are specific
for severe MR
Other findings are nonspecific
Regurgitant Color Flow
Easy to use, evaluates spatial
orientation of MR jet,
differentiates mild versus
severe
Subject to technical and
hemodynamic variation; can
be underestimated with wallimpinging jets (Coanda
effect); image qualitydependent
Vena Contracta Width
Quick and easy to use;
independent of hemodynamic
and instrumentation factors;
applies to eccentric jets; can
differentiate mild versus
severe MR
Not applicable to multiple jets,
intermediate values require
confirmation; small
measurement errors can lead
to big changes; 2D measure of
a 3D structure
Proximal Isovelocity Surface
Area (PISA)
Can be applied to eccentric
jets (when angle corrected);
not affected by etiology of
MR; quantitative: provides
both lesion severity (EROA)
and volume data (R Vol); flow
convergence at Nyquist limit
of 50–60 cm/s alerts reader to
significant MR
Not valid with multiple jets;
provides peak flow and
maximal EROA; interobserver variability; errors in
radius measurement are
squared; multiple potential
sources of measurement error
Flow Quantitation–PW
Quantitative; valid in multiple
jets and eccentric jets;
Time consuming;
measurement of flow at MV
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provides both lesion severity
(EROA, RF) and volume data
(RVol)
annulus less reliable with
calcified MV and/or annulus;
not valid with concomitant
significant AR unless
pulmonic site is used; requires
measurement at multiple sites,
which introduces errors
Jet Profile–CW
Simple, readily available
Qualitative; complementary
data; complete signal difficult
to obtain in eccentric jet; gain
dependent
Peak Mitral E Velocity
Simple, readily available, Awave dominance excludes
severe MR
Influenced by LA pressure,
LV relaxation, MV area, and
AF; complementary data only,
does not quantify MR severity
Pulmonary Vein Flow
Simple; systolic flow reversal
is specific for severe MR
Influenced by LA pressure,
AF; not accurate if MR jet
directed into the sampled vein;
absence does not rule out
severe MR
LA and LV Size
Enlargement sensitive for
chronic severe MR, important
for outcomes; normal size
virtually excludes severe
chronic MR
Enlargement seen in other
conditions (non-specific); may
be normal in acute severe MR
1
2
3
Abbreviations: AF = atrial fibrillation; AR = aortic regurgitation; CW = continuous wave; EROA = effective
regurgitant orifice area; LA = left atrium; LV = left ventricle; MR = mitral regurgitation; MV = mitral valve; RF =
regurgitant fraction; RVol = regurgitant volume
4
Right and left heart catheterization may be indicated to assess hemodynamics;
5
despite its known limitations, a high quality biplane LV angiogram can also be helpful in
6
resolving uncertainty. Invasive measurement of pressures, cardiac output and pulmonary
7
vascular resistance allows a comprehensive assessment, results of which can be
8
correlated with symptoms and response to medical therapy. Stress echocardiography can
9
also be a valuable tool to assess any discrepancies between non-invasive and clinical
10
findings and help define symptoms, exercise capacity, MR severity, pulmonary artery
30
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
systolic pressure and LV/RV responses to exercise. High quality CMR can be very
2
helpful in many patients in whom MR severity is unclear, though the technology is not
3
widely available. Consideration should be given to referring such patients to a
4
comprehensive valve center for multidisciplinary evaluation and treatment.
5
An evidence-based algorithm for the evaluation and management of patients with
6
MR is outlined in Figure 8. Based on the 2014 ACC/AHA Guidelines for the
7
Management of Patients with Valvular Heart Disease (1), this algorithm attempts to
8
mitigate any potential gaps in the clinical approach to MR (19). Decisions as to when to
9
follow and when to refer patients with MR for further assessment or valve intervention
10
can be challenging. Once the diagnosis of MR is established by TTE, the next steps are to
11
establish the clinical context and symptomatology, the etiology of MR (primary vs.
12
secondary vs. mixed), and its severity using the integrative methods previously outlined.
13
This expert consensus algorithm provides a roadmap for the clinician to navigate
14
decision-making for additional testing or referral for definitive treatment. The latter is
15
discussed further below.
16
17
31
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1
Figure 8. Clinical Algorithm for the Management of MR based on TTE
2
3
4
5
Note: Please see another attachment for the high resolution image
32
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
6.4.4 Dynamic Nature of MR
MR is a dynamic condition and its severity can change with LV load (49). Sedation and
3
reduced blood pressure during TEE may result in a significant reduction in MR severity,
4
compared to an assessment with TTE in the awake state. Patients with hypertensive
5
urgency can present with moderate or severe MR that resolves completely with control of
6
blood pressure. On the other hand, MR severity can increase with maneuvers that
7
decrease LV afterload in patients with mitral valve prolapse (57) or hypertrophic
8
obstructive cardiomyopathy. Guideline-directed medical therapy, revascularization, and
9
cardiac resynchronization may improve MR severity in functional MR, particularly if
10
such interventions result in reverse LV remodeling or improved regional wall motion. In
11
addition to changing over time, MR severity is dynamic within the cardiac cycle (50,51).
12
The classic example is late systolic MR due to prolapse. It is important to recognize this
13
phenomenon because single frame measurements on TTE or TEE may overestimate MR
14
severity. In such circumstances, EROA or RVol should be measured with volumetric
15
techniques that include all of systole (38). It is possible to correct EROA for duration of
16
systole, but this method has not been validated. In secondary MR, a biphasic pattern can
17
be seen in which MR improves during mid-systole when LV pressure (i.e. closing force)
18
is at its maximum (50). It is important for the sonographer not to “overgain” the machine
19
to make this phenomenon disappear. It is also important to measure PISA radius and MR
20
peak velocity at the same point in the cardiac cycle (2). CFD measures of MR severity
21
can vary significantly during rapid AF or with large variations in the R-R interval.
22
Likewise, caution must be used to avoid measuring MR during PVCs or post-PVC beats.
23
Early systolic or late diastolic MR can occur with conduction system abnormalities and
33
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
this should be recognized as a potential source of overestimating MR severity by single-
2
frame technique (58).
3
4
6.4.5 Differences in Assessing MR Severity in Primary vs. Secondary MR
Primary MR is generally easier to evaluate because of the morphological abnormalities of
5
the mitral leaflets or chordae. Some morphological abnormalities, such as a flail leaflet
6
with torn chords, severe leaflet retraction without visible coaptation, or leaflet destruction
7
and perforation due to endocarditis, are specific markers of severe MR. LV or LA
8
dilation in chronic primary MR is most often a consequence of the MR and a strong clue
9
that the MR is severe. Exceptions could occur if a patient with long-standing mitral valve
10
prolapse and mild MR develops an ischemic or nonischemic cardiomyopathy. On the
11
other hand, when MR is primary and LV and LA size are normal, severe MR is very
12
unlikely. Secondary MR is more difficult to grade because morphological abnormalities
13
of the leaflets and chords are absent. Symptoms, pulmonary congestion on exam or chest
14
x-ray, elevated BNP or NT-pro-BNP and adjunctive findings on TTE or TEE, such as LV
15
or LA dilation and systolic blunting of the pulmonary venous flow pattern may be due to
16
the underlying cardiomyopathy and therefore are less helpful in grading MR severity.
17
Further confounding this situation is the fact that in secondary MR, the shape of the
18
regurgitant orifice is often markedly crescentic, which leads to underestimation of EROA
19
by the PISA method because the latter assumes a round orifice (39-48). This inaccuracy
20
can be ameliorated by 3D PISA measurements or direct 3D measurement of EROA by
21
TTE or TEE. Such measurements have been validated against CMR (45,47).
22
Importantly, EROA and RVol thresholds that constitute severe MR are related to LV
23
volumes (59). As an example, consider two patients with LVEF 30%, but LV end-
24
diastolic volumes of 200 mL and 400 mL, respectively. The former has a total stroke
34
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
volume of 60 mL; the latter 120 mL. In the former patient, an EROA of 0.3 cm2 with a
2
MR velocity-time integral of 150 cm yields an RVol of 45 mL. Although these values
3
are in the traditional range of moderate MR, they constitute a RF of 75% (45mL/60mL),
4
consistent with severe MR and loss of 3/4ths of forward cardiac output into the LA. In
5
the latter patient, the same values (EROA 0.3 cm2 and RVol 45 ml) would yield a RF of
6
37.5%, consistent with moderate MR. Thus, consideration of quantitative values for MR
7
severity should also account for LV volumes and ejection fraction.
8
9
6.4.6 Prognosis in MR
Table 3 lists prognostic variables important in the assessment of primary MR. Some of
10
these are clinical (age, heart failure, coronary artery disease, and functional class).
11
Others relate to MR itself or the effects of MR on the LV or LA. LVEF < 60%, LV end-
12
systolic diameter > 0.4 cm, or LA systolic volume index > 60 mL/m2 have all been
13
associated with worse prognosis (60-63). Flail leaflet itself is associated with an adverse
14
prognosis and is usually a specific sign for severe MR (5,60,61), although occasionally
15
patients with flail leaflets only have moderate MR by integrative assessment. Rare
16
patients with flail leaflet may experience sudden cardiac death (64) and consideration
17
could be given to earlier treatment referral. Secondary MR has been associated with an
18
adverse prognosis in multiple studies (10-17). In ischemic cardiomyopathy, the presence
19
of MR of any grade results in worse long-term prognosis, but severe ischemic MR is also
20
an indicator of short-term mortality. An EROA ≥ 0.2 cm2 has been shown to be a
21
predictor of adverse outcomes in some but not all studies of patients with functional MR
22
(11,14,16). Importantly, it appears that secondary MR is an independent marker of
23
adverse prognosis, even when LV volumes, LVEF, renal function, and other parameters
35
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
are included in multivariable analysis (12,15). Surgical correction of secondary MR may
2
improve symptoms and quality of life, but has not been shown to improve survival (65).
3
Table 3. Factors Affecting Prognosis in Primary MR
Primary MR
1. Factors related to the LV or LA



2. Clinical factors




Systolic dysfunction (EF < 60%)
LV enlargement (LVESD > 4cm)
LA enlargement (LA systolic
volume index ≥ 60 ml/m2)
Age
Presence/absence heart failure
Functional class
Presence/absence CAD
3. Hemodynamic (other) factors


AF
Pulmonary hypertension
4. Factors related to the MR

Severity of regurgitation flail
leaflet
Delay in MV intervention

4
5
Abbreviations: AF = atrial fibrillation; CAD = coronary artery disease; EF = ejection fraction; LA = left atrium; LV =
left ventricle; LVESD = left ventricular end-systolic diameter; MR = mitral regurgitation; MV = mitral valve
6
6.5. Treatment of Chronic Mitral Regurgitation
7
8
Deciding on the optimal treatment of chronic MR is based on multiple variables
9
including MR type and severity, hemodynamic consequences, disease stage, patient co-
10
morbidities and the experience of the managing physician/surgeon (66). Evidence-based
11
management may be aided by use of the algorithm in Figure 8. Reporting
12
echocardiographic findings using standardized nomenclature helps guide
13
surgical/interventional decision-making (31). The anterior and posterior leaflets are
14
divided into three anatomic sections from lateral to medial (A1, A2, A3, and P1, P2, P3,
15
respectively). The two leaflets meet at the lateral and medial commissures, where focal
16
pathology (e.g., calcification) may occur. The chordal structures may have excess or
36
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
restricted motion and are defined by their leaflet insertion as primary (leading edge
2
insertion), secondary (mid-scallop insertion), and tertiary (basal insertion). A well-
3
performed TTE is sufficient for treatment planning in most instances. The majority of
4
information needed to complete surgical/interventional planning can be obtained with 4
5
conventional TEE views: the mid-esophageal 4-chamber, long-axis 2-chamber, mid-
6
commissural 2-chamber and the basal short-axis view. Though focused use of CFD at a
7
Nyquist of 50-60 cm/sec may aid in mechanism confirmation, planning for intervention
8
should be based on imaging without color in each of these views.
9
The principal treatment modality for primary MR is surgery. Transcatheter mitral
10
repair using an edge-to-edge clip has a very limited role at present for the treatment of
11
patients with primary MR and severe symptoms who are felt to be poor surgical
12
candidates. Surgical treatment for secondary MR is undertaken only after appropriate
13
medical and device therapies have been instituted. Transcatheter repair systems other
14
than the edge-to-edge clip, as well as transcatheter mitral valve replacement devices,
15
currently are not approved for clinical use in the United States but remain the subject of
16
clinical trial investigation.
17
18
6.5.1. Surgical Treatment of Mitral Regurgitation
Mitral valve surgery is indicated in patients with primary severe MR and EF > 30% who
19
are symptomatic (Stage D) or when asymptomatic but with LVEF 30%-60% or LV end-
20
systolic dimension > 4.0cm (Stage C2) (1). Mitral valve repair is strongly preferred over
21
replacement for primary MR whenever anatomically feasible and as dictated by the
22
experience and skill of the operating surgeon. Mitral valve repair is reasonable in patients
23
with primary MR and preserved LV size and systolic function when AF has recently (< 3
24
months) intervened or when resting PA pressures are elevated (>50 mm Hg at rest).
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EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
Mitral valve repair is also reasonable for asymptomatic patients with normal LV size and
2
function when the likelihood of a successful and durable repair without residual MR
3
exceeds 95% and operation can be performed with <1% mortality at a comprehensive
4
heart valve center. Short- and long-term outcomes of successful valve repair for primary
5
MR exceed those for valve replacement across all age ranges. Successful repair at the
6
indicated time results in long-term survival equivalent to that of the normal age-matched
7
population (67,68). Timely surgical referral for primary MR must take into account the
8
feasibility of repair and knowledge of surgeon and institutional outcomes. The latter is
9
particularly relevant when considering referral of an asymptomatic patient.
10
Indications for mitral valve surgery for moderate or severe functional MR are
11
more limited, in part related to the recognition that valve intervention in this patient
12
group may improve symptoms and quality of life, but does not currently equate with
13
improved survival. Mitral valve repair (usually with an under-sized annuloplasty ring)
14
may be considered at the time of other cardiac surgery (e.g., CABG) for patients with
15
moderate functional MR. In patients with severe functional MR, mitral valve surgery
16
(either replacement or repair) is reasonable at the time of other cardiac surgery (e.g.,
17
CABG) and can be considered as an isolated procedure for patients with advanced
18
NYHA class despite guideline-directed medical therapy and cardiac resynchronization
19
when indicated. The decision to replace or repair the valve can be challenging (65) and is
20
deferred to an experienced surgeon in consultation with the heart valve team.
38
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
6.5.2. Feasibility of Surgical Repair
2
3
4
Figure 9. Decision Tree for Determining Surgical Mitral Valve Repair vs.
Replacement in Patients with Severe MR
5
39
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1
Mitral valve repair is a complex operation comprising a wide spectrum of available
2
techniques to achieve durable success (69). The principal goals of mitral valve repair are
3
to restore leaflet coaptation depth to greater than 5 mm, stabilize and remodel the
4
annulus, restore normal leaflet motion, and eliminate MR. The major factors determining
5
repair feasibility are pathoanatomy and surgeon experience.
6
The surgical spectrum of primary MR with Carpentier type II motion ranges from
7
focal prolapse in the setting of an otherwise anatomically normal mitral valve, known as
8
fibroelastic deficiency, to a more diffuse process with excess, redundant, billowing tissue
9
as noted in Barlow’s syndrome (70) or an intermediate between these 2 extremes referred
10
to as a forme fruste. In primary MR with Carpentier type IIIA motion, the surgical
11
spectrum includes focal or diffuse leaflet and subvalvular thickening and commissural
12
fusion due to rheumatic heart disease, prior radiation or other inflammatory conditions.
13
Both of these causes of primary MR may occur in the same patient, potentially affecting
14
repair feasibility, and highlighting the critical importance of preoperative imaging.
15
Common techniques of mitral valve repair are listed in Table 4 and include construction
16
of artificial neochordae with polytetrafluoroethylene or limited triangular resection as
17
applied in cases of focal prolapse or fibroelastic deficiency, and extensive posterior
18
leaflet resection and remodeling in cases of diffuse myxomatous degeneration and
19
echocardiographic predictors of post-operative systolic anterior motion of the anterior
20
mitral valve leaflet. A suggested approach to determine the feasibility and complexity of
21
repair is described in Table 5. Patients presenting with echocardiographic findings of
22
focal posterior prolapse or flail without annular or leaflet calcium often have a high
23
success rate for durable repair by the majority of experienced valve surgeons. However,
40
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
once additional annular, commissural or bileaflet pathoanatomic complexities arise, in
2
isolation or combination, more specific experience with mitral valve repair may often be
3
required to achieve a technically successful and durable result. Other confounding factors
4
impacting reparability that may necessitate advanced mitral surgical evaluation include
5
mitral reoperations, prior mitral endocarditis, basal septal hypertrophy with
6
echocardiographic predictors of post-operative systolic anterior motion of the anterior
7
mitral leaflet and congenital anomalies. Patients who have a single segment flail of the
8
posterior leaflet due to fibroelastic deficiency in the absence of calcification of the
9
annulus or leaflets have the highest chance of technically successful and durable valve
10
repair. These patients should not undergo valve replacement (1). Alternatively, patients
11
with severe anterior, bileaflet, Barlow’s or mixed disease that may require extensive and
12
complex reparative techniques should be preferentially referred to an experienced mitral
13
valve surgeon at a high volume institution. There is a small subgroup of patients with
14
primary MR in whom valve replacement may be preferred over valve repair, such as
15
those who have had prior cardiac operation or prior chest radiation, in whom any
16
subsequent operation for a failed repair would be undertaken at substantially increased
17
risk. Figure 9 provides a more detailed guide to decision-making for mitral repair or
18
replacement based on Carpentier’s classification. Figure 10 shows echocardiographic
19
examples of mitral valve morphologies that are likely, possible or challenging for
20
successful and durable mitral valve repair. Surgeon experience has been recognized as a
21
primary determinant of successful mitral valve repair. Registry data from 2005 to 2007
22
estimated a nearly 3-fold likelihood of repair when surgeon experience was over 100
23
cases per year compared to 5-10 per year, with a threshold for frequency of successful
41
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
repair being over 50 mitral surgical cases per year (repair or replacement) (71). However,
2
data from the last 5 years have shown a doubling of the frequency of mitral valve repair
3
over replacement, and the initial success rate for isolated mitral valve repair for primary
4
MR is now over 75% across the United States (69,72). Nevertheless, for asymptomatic
5
Stage C1 patients or for those with complex mitral pathoanatomy, or for patients who
6
desire a minimally invasive or robotic approach, consideration should be given to referral
7
to an experienced mitral surgeon at a comprehensive valve center (1).
8
9
10
Table 4: Pathoanatomically Directed Contemporary Surgical Techniques for Mitral
Regurgitation
Primary Mitral Regurgitation
1.
Non-resection techniques using polytetrafluorethylene (PTFE) neochord reconstruction
with annuloplasty ring
 May be used for focal leaflet flail or bileaflet prolapse
 May be used for forme fruste* diffuse myxomatous disease of the posterior leaflet
 May be used for isolated anterior leaflet prolapse
2.
Focal triangular resection with annuloplasty ring
 May be used for focal leaflet flail of the posterior or commissural leaflet
3.
Sliding leaflet valvuloplasty with annuloplasty ring
 May be used for forme fruste* diffuse posterior leaflet myxomatous disease
 May be used in the setting of bileaflet prolapse with excess posterior leaflet
 May be used in any of the above with significant echocardiographic predictors of
systolic anterior motion of the anterior mitral valve leaflet
Secondary Mitral Regurgitation
11
12
13
14
1.
Restrictive remodeling rigid annuloplasty ring
 May be used as primary modality for annular dilatation mechanism
 May be used in conjunction with secondary or tertiary chordal cutting
 May be used with other adjunctive procedures (i.e., papillary muscle sling)
 Avoided as sole therapy in setting of Carpentier Type IIIB mechanism with left
ventricular inferobasal aneurysm
2.
Chord-sparing mitral valve replacement
 May be used as primary modality for annular dilatation with severe leaflet tethering
(i.e., ≥ 10 mm tenting height) or presence of inferobasal aneurysm
* See text. Forme fruste refers to a pathoanatomic form of primary MR intermediate between fibroelastic deficiency
and Barlow’s disease.
42
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
Table 5. Feasibility of Transcatheter Edge-to-Edge Clip Repair
3
4
Abbreviations: BSA = body surface area; EROA = effective regurgitant orifice area; HOCM = hypertrophic obstructive cardiomyopathy; MAC = mitral annular calcification.
5
Note: Transcatheter edge-to-edge clip repair is approved for use in the United States only for patients with primary MR, severe symptoms and high or prohibitive operative risk.
6
Adapted from Hahn, R (73).
43
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Figure 10. Examples of Valve Morphology that is Amenable to Surgical Repair in
Patients with Primary MR
Figure 10. TEE images showing examples of primary mitral valve pathology with different
likelihood of durable surgical repair. Long-axis views (left panels), bicommissural views (middle
panels) and 3D en face views (right panels) are shown. At top, durable surgical repair is likely
with thin, pliable leaflets (yellow arrow, left panel) with torn chords to the posterior middle
scallop (P2) seen in the middle (blue arrow) and right panels (yellow arrows). Durable surgical
repair is possible in the middle panel. Both anterior and posterior leaflets exhibit marked
prolapse (yellow arrows, left panel) involving multiple scallops with torn chords (middle panel,
blue arrow, right panel, yellow arrows). The annulus is severely dilated. The bottom panel
shows a patient for whom durable repair is challenging due to severe mitral annular and leaflet
calcification (yellow arrows) with restricted leaflet excursion (right panel). In addition to severe
MR, this patient had a mean transmitral gradient 14 mmHg at a resting heart rate of 68 min-1.
18
19
6.5.3. Determination of Risk for Surgery
When a patient is being evaluated for treatment of MR, a key component is an assessment
20
of the individual’s risk for surgical mitral valve repair or replacement. Evaluation
21
includes the use of a standardized Predicted Risk of Mortality (PROM) developed by The
44
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
Society of Thoracic Surgeons based on the outcomes of large numbers of patients who
2
have undergone surgery (72,74). There are additional factors not included in this risk
3
score that contribute to procedural and post-procedural risk including liver disease,
4
pulmonary hypertension, porcelain aorta and post-radiation scarring, as well as the
5
patient’s ability to recover from the trauma of surgery due to frailty. Measures of frailty
6
such as the 5-meter or 6-minute walk test and hand grip strength have become part of the
7
routine evaluation of elderly patients in whom recommendations must be made
8
considering surgical and transcatheter approaches incorporating the clinical judgment of
9
the heart team. The AHA/ACC 2014 Guideline for the Management of Patients with
10
Valvular Heart Disease include a risk assessment tool that incorporates these
11
considerations.
12
13
6.5.4. Transcatheter Treatment of Mitral Regurgitation
The desirability of transcatheter options for the treatment of mitral regurgitation is driven
14
by the increasing prevalence of this valve lesion among an aging population with
15
significant co-morbidities that render many patients poor candidates for surgical
16
intervention. Lower risk procedures that effectively reduce the severity of mitral
17
regurgitation and provide a means to improved clinical outcomes are the goals of
18
transcatheter interventions.
19
The complex, functional anatomy of the mitral apparatus has challenged the
20
development of effective transcatheter strategies for the management of MR. There is
21
wide inter-patient variability in the individual contributions of each component (leaflets,
22
annulus, chordae, papillary muscles and subjacent myocardium) to the emergence and
23
progression of MR. Transcatheter repair techniques can be targeted to the leaflets,
45
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
annulus or chordae, either solely or in combination. Transcatheter mitral valve
2
replacement remains investigational (75-77). At present, edge-to-edge mitral leaflet
3
coaptation using a clip to approximate opposing segments of the anterior and posterior
4
leaflets is the only FDA-approved system for transcatheter repair in the United States
5
(78,79). Furthermore, its use is restricted to the management of symptomatic (NYHA
6
Class III or IV) patients with severe, primary MR, reasonable life expectancy and
7
prohibitive surgical risk due to co-morbidities (1,79). The safety and efficacy of this
8
technology for the treatment of patients with symptomatic, severe functional MR is being
9
studied in a randomized controlled trial [Cardiovascular Outcomes Assessment of the
10
MitraClip Percutaneous Therapy (COAPT) Trial (NCT 01626079)], results of which are
11
expected in 2020. Edge-to-edge leaflet repair for patients with functional MR is used
12
more frequently in centers outside the United States (80). Several other transcatheter
13
repair systems are in development (e.g., annular devices) but are not currently available
14
for clinical use (76). This area is likely to change rapidly over time.
15
16
6.5.5. Edge-to-Edge Leaflet Coaptation
Transcatheter edge-to-edge leaflet coaptation using a clip is based on the surgical
17
technique described by Alfieri (81) and results in creation of a double orifice mitral valve
18
and reduction in the severity of MR (Figure 11). Successful deployment can result in
19
improved hemodynamics and patient outcomes. Appropriate patient selection is critically
20
dependent on rigorous clinical and echocardiographic assessment (Figure 12). Intra- and
21
post-procedural management algorithms facilitate best practices. Operator and
22
institutional criteria for the performance of transcatheter mitral valve repair have been
23
published in a joint, multi-societal expert consensus document (3).
24
46
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
Figure 11. Transcatheter Edge-to-Edge Mitral Valve Clip
3
4
5
6
7
8
9
Figure 11. Transcatheter edge-to-edge mitral valve clip. Top left. 3D en face view showing flail
anterior leaflet with torn chord (arrow). Top right. Transcatheter edge-to-edge clip creates tissue
bridge between anterior and posterior leaflets (arrow). Bottom left. Color flow image showing
severe MR at beginning of case. Bottom right. Reduction of MR from severe to trace after
transcatheter edge-to-edge clip placement.
10
47
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
Figure 12. Algorithm for Determining Eligibility for Transcatheter Edge-to-Edge
Mitral Valve Clip
3
4
5
6.5.6. Feasibility of Edge-to-Edge Leaflet Coaptation
Figure 13 and Table 1 include the key echocardiographic parameters used to assess
6
suitability for transcatheter edge-to-edge repair (73). The procedure is usually performed
7
by 1or 2 operators in a cardiac catheterization laboratory or hybrid suite. A multi-
8
disciplinary team, which includes at a minimum a clinical heart valve specialist, multi-
9
modality cardiac imaging expert, interventional cardiologist and cardiac surgeon, is
10
required for patient evaluation, selection and periprocedural management. Other
11
transcatheter mitral valve repair systems for primary MR may become available for
12
clinical use in future years and dictate new requirements for patient assessment and
13
selection.
48
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
Figure 13. Transcatheter Edge-to-Edge Mitral Valve Clip
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Figure 13. TEE images showing examples of mitral anatomy with varying degrees of difficulty
for transcatheter edge-to-edge clip therapy. Top Left: 3D en face View Showing Flail Anterior
Leaflet with Torn Chord (Arrow). Top Right: Transcatheter Edge-to-Edge Clip Creates Tissue
Bridge between Anterior and Posterior Leaflets (Arrow). Bottom Left: Color Flow Image
Showing Severe MR at Beginning of Case. Bottom Right: Reduction of MR from Severe to
Trace after Transcatheter Edge-to-Edge Clip Placement. Left panels are long-axis view, middle
panels bicommissural views, and right panels 3D en face views. The top panel shows anatomy
for which successful repair is likely. The posterior middle scallop (P2) is flail (arrows) with
normal leaflet thickness and no mitral annular calcification. The middle panel is a challenging
case with no significant pathology of the middle segments (long-axis) but flail P1 and P3
2
segments (arrows). The diastolic mitral area was 4.8 cm , allowing room for clips in both
commissures. The bottom panel shows a patient with severe mitral annular calcification (yellow
2
arrows) and a flail P3 segment (blue arrows). The mitral valve area was 2.8 cm , which is below
2
the threshold value (4.0 cm ) and would likely result in mitral stenosis.
7. DISCUSSION AND IMPLICATION OF PATHWAY
21
22
The last several years have witnessed important advances in the evaluation and
23
management of patients with chronic MR. Building upon the 2014 AHA/ACC Guideline
24
for the Management of Patients with Valvular Heart Disease, the material in this expert
49
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
consensus document serves to provide the clinician with additional tools to improve the
2
care of MR patients. Multidisciplinary heart teams composed of experienced surgeons,
3
interventionalists, expert imagers and others are vital to the provision of advanced care to
4
challenging patients at comprehensive valve centers. Closing the existing knowledge and
5
treatment gaps in the management of these patients, as well as the achievement of high
6
value care, requires ongoing close collaboration across primary care, cardiology and
7
cardiac surgical communities, as emerging technologies for the treatment of mitral valve
8
disease are evaluated with a dedicated focus on high quality outcomes.
9
Key Points
10

11
12
using quantitative echocardiography and other testing as indicated.

13
14

The prognostic, evaluative and management differences between primary and
secondary (functional) MR should be recognized.

17
18
Standardized echocardiographic reporting is critical for informed patient
management.
15
16
Once MR is recognized, its etiology, mechanism and severity should be defined
A heart valve team consensus treatment recommendation should be discussed
with the patient and family to enable shared decision-making.

The indications for and techniques utilized in surgical treatment of primary and
19
secondary MR differ. For patients with severe primary MR, referral for repair to
20
an experienced mitral valve surgeon at a comprehensive valve center should be
21
considered when pathoanatomic findings include lesions other than isolated
22
posterior segment pathology.
50
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1

Current use of the edge-to-edge clip in the United States for transcatheter mitral
2
valve repair is limited to symptomatic patients with primary, severe MR who are
3
poor operative candidates. Other transcatheter systems are under investigation.
4

5
6
7
Evidence-based medical therapy should be optimized in patients with secondary
(functional) MR before decision-making for surgical intervention.

Long-term follow-up of patients after surgical or transcatheter intervention is
critical for assessment of durability, functional outcomes and survival.
51
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
1
2
3
4
5
6
7
8
9
10
11
PRESIDENTS AND STAFF
Richard Chazal, MD, FACC, President
Shalom Jacobovitz, Chief Executive Officer
William J. Oetgen, MD, MBA, FACC, Executive Vice President, Science, Education,
Quality, and Publications
Joseph M. Allen, MA, Team Leader, Clinical Policy and Pathways
Lea G. Binder, MA, Team Leader, Physician Clinical Pathways
Sahisna Bhatia, MPH, Project Manager, Clinical Policy and Pathways
Amelia Scholtz, PhD, Publications Manager, Science, Education, Quality, and
Publications
52
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
APPENDIX 1: Author Relationships With Industry and Other Entities (Relevant) — 2017 ACC Expert Consensus
Decision Pathway on the Assessment of Mitral Regurgitation
Relationships with Industry and Other Entities
To avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests
among the writing committee, all members of the writing committee, as well as peer reviewers of the document, are asked to disclose
all current healthcare-related relationships, including those existing 12 months before initiation of the writing effort. The ACC Task
Force on Clinical Expert Consensus Documents reviews these disclosures to determine what companies make products (on market or
in development) that pertain to the document under development. Based on this information, a writing committee is formed to include
a majority of members with no relevant relationships with industry (RWI), led by a chair with no relevant RWI. RWI is reviewed on
all conference calls and updated as changes occur. Author RWI pertinent to this document is disclosed in the table below and peer
reviewer RWI is disclosed in Appendix B. Additionally, to ensure complete transparency, authors’ comprehensive disclosure
information— including RWI not pertinent to this document—is available online (see Online Appendix). Disclosure information for
the ACC Task Force on Clinical Expert Consensus Documents is also available online at http://www.acc.org/guidelines/aboutguidelines-and-clinical-documents/guidelines-and-documents-task-forces, as well as the ACC disclosure policy for document
development at http://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy.
Committee
Member
Patrick T.
O’Gara
(Chair)
Employment
Consultant
Harvard Medical School—
Professor of Medicine;
Brigham and Women’s
Hospital—Director,
Clinical Cardiology
 National
Institutes of
Health*
Speakers
Bureau
None
Ownership/
Partnership/
Principal
None
53
Personal
Research
None
Institutional,
Organizational, or
Other Financial
Benefit
None
Expert Witness
None
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
Committee
Member
Employment
Paul A.
Grayburn
(Vice-Chair)
Baylor Heart and Vascular
Institute—Director,
Cardiology Research
 Abbott
Vascular*
 American
Journal of
Cardiology
 Bracco
 Tendyne
None
None
 Abbott
Vascular†
 Edwards†
 Guided Delivery
Systems†
 Medtronic†
 Tendyne†
Valtech Cardio†
Vinay
Badhwar
(Vice-Chair)
West Virginia University—
Gordon F. Murray
Professor and Chair,
Department of
Cardiovascular & Thoracic
Surgery; Executive Chair
WVU Heart & Vascular
Institute
Wayne State University,
Division of Cardiology—
Professor of Medicine
None
None
None
None
 On-X Technologies None
 Edwards
Lifesciences
 Abbott
Vascular/Tendyne
Inc.
 Zoll Medical None
Corporation†
None
None
None
University of Colorado
Denver—Professor of
Medicine; Director,
 Philips
Healthcare*
 St. Jude
None
 Evalve/Abbott*
 Philips
Healthcare*
None
Luis C.
Afonso
John D.
Carroll
Consultant
Speakers
Bureau
None
Ownership/
Partnership/
Principal
54
Personal
Research
Institutional,
Organizational, or
Other Financial
Benefit
 Abbott Vascular*
 Baylor Healthcare
System
Foundation*
 Guided Delivery
Systems*
 Medtronic*
 National Institutes
of Health*
Valtech Cardio*
Expert Witness
None
 Third Party,
fatal stroke
post
operatively
after hip
replacement,
2014
None
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
Committee
Member
Employment
Interventional Cardiology
Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Medical*
Sammy
Elmariah
Massachusetts General
Hospital—Cardiologist,
Department of Medicine
None
None
None
Aaron P.
Kithcart
Brigham and Women’s
Hospital, Division of
Cardiovascular Medicine—
Cardiovascular Disease
Fellow
None
None
None
Rick A.
Nishimura
Mayo Clinic, Division of
Cardiovascular Disease—
Judd and Mary Morris
Leighton Professor of
Medicine
None
None
Thomas
John Ryan
Ohio State Heart and
Vascular Center
None
None
Personal
Research
 St. Jude
Medical*
 Tendyne
(DSMB) †
 Siemens
Healthcare*
Institutional,
Organizational, or
Other Financial
Benefit
Expert Witness
None
None
None
None
None
None
None
None
None
None
 core lab for
RCTs*
 Edwards
Lifesciences
 Medtronic
 ABIM
None
Ross Heart Hospital—John
G. and Jeanne Bonnet
McCoy Chair in
55
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
Committee
Member
Employment
Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational, or
Other Financial
Benefit
Expert Witness
Cardiovascular Medicine;
Director
Allan
Schwartz
Columbia University—
Chief, Division of
Cardiology
None
None
None
None
None
None
Lynn
Warner
Stevenson
Brigham and Women’s
Hospital—Director,
Cardiomyopathy and Heart
Failure Program
 St. Jude
Medical
 American
Heart
Association†
None
None
 St. Jude
Medical†
 NHLBI
INTERMACS–
Co-PI†
 NHLBI †
None
None
This table represents all relationships of committee members with industry and other entities that were reported by authors, including those not deemed to be relevant to this document, at the
time this document was under development. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a
business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of ≥$5,000 of the fair market value of the business entity; or if funds
received by the person from the business entity exceed 5% of the person’s gross income for the previous year. Relationships that exist with no financial benefit are also included for the
purpose of transparency. Relationships in this table are modest unless otherwise noted. Please refer to http://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationshipswith-industry-policy for definitions of disclosure categories or additional information about the ACC Disclosure Policy for Writing Committees.
*Significant relationship.
†No financial benefit.
ACC indicates American College of Cardiology; DSMB, Data Safety Monitoring Board; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; NHLBI,
National Heart, Lung, and Blood Institute.
56
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
APPENDIX 2: Peer Reviewer Relevant RWI
[TO BE ADDED BY STAFF]
57
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
APPENDIX 3: Abbreviations
ACC = American College of Cardiology
AF = Atrial Fibrillation
CFD = Color Flow Doppler
ECDP = Expert Consensus Decision Pathways
EROA = Effective Regurgitant Orifice Area
LA = Left Atrial
LV = Left Ventricular
LVEF = Left Ventricular Ejection Fraction
MR = Mitral Regurgitation
RVol = Regurgitant Volume
TEE = Transesophageal Echocardiography
TTE = Transthoracic Echocardiography
58
EXPERT CONSENSUS DECISION PATHWAY – CONFIDENTIAL AND EMBARGOED
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