Seminars in Cardiothoracic and Vascular Anesthesia 2019, Vol. 23(1) 11–19 © The Author(s) 2018 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1089253218792921 journals.sagepub.com/home/scv Article Background The terms secondary, functional, and ischemic mitral regur- gitation (MR) are often used interchangeably as a means to differentiate from primary or degenerative MR, which is defined as regurgitation caused by pathology of the mitral valve (MV) leaflets and/or supporting chordae. In pure sec- ondary MR, the MV leaflets and chords are themselves normal; 1 however, leaflet coaptation is hindered by struc- tural and functional abnormalities of the left ventricle. 1,2 Furthermore, annular dilation and reduced systolic closing force by the ailing left ventricle contribute to malcoaptation and secondary MR. 2,3 Table 1 summarizes the differences between primary and secondary MR. 2 Ischemic MR is a subset of secondary MR in which the etiology of left ven- tricular dysfunction is a result of coronary artery disease and associated myocardial ischemia and infarction. 1 Although ischemic MR will be the focus of this review, it is important to recognize that there are nonischemic causes of left ventricular dysfunction that can lead to secondary MR. The 2014 American Heart Association/American College of Cardiology (AHA/ACC) Guideline for the Management of Patients With Valvular Heart Disease stratified secondary MR into 4 stages: at risk of MR (Stage A), progressive MR (Stage B; asymptomatic, nonsevere MR), asymptomatic severe MR (Stage C), and symptom- atic severe MR (Stage D). 2 Stage D differs from stage C by the persistent symptoms of severe MR even after coronary revascularization and adherence to guideline-prescribed medical therapy. It is noteworthy that in the 2014 guide- lines, stages C and D secondary MR (ie, severe MR) were defined by quantitative valve hemodynamic thresholds of effective regurgitant orifice area (EROA) ⩾0.20 cm 2 , regurgitant volume ⩾30 mL, and regurgitant fraction ⩾50%. However, in the 2017 AHA/ACC Focused Update of the 2014 guidelines, the quantitative thresholds specify- ing severe secondary MR were redefined to match the val- ues of primary MR (EROA ⩾0.40 cm 2 , regurgitant volume ⩾60 mL, and regurgitant fraction ⩾50%). 4 Table 2 out- lines the differences between the 2014 and 2017 AHA/ ACC guidelines. 2,4 The intent of the 2014 guidelines to define severe sec- ondary MR with lower hemodynamic thresholds compared with primary MR appears to have been driven by a couple of factors. 5 First, studies such as ones by Rossi et al have shown worse outcomes in patients with severe secondary MR when defined as EROA ⩾0.20 cm 2 or regurgitant vol- ume ⩾30 mL compared with those with EROA <0.20 cm 2 or regurgitant volume <30 mL. 6 Second, the echocardio- graphic technique of assessing proximal isovelocity surface area (PISA) has long been the traditional method to measure 792921SCV XX X 10.1177/1089253218792921Seminars in Cardiothoracic and Vascular AnesthesiaNonaka and Fox research-article 2018 1 University of Texas Southwestern Medical Center, Dallas, TX, USA Corresponding Author: Daisuke F. Nonaka, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8894, USA. Email: [email protected] Ischemic Mitral Regurgitation: Repair, Replacement or Nothing Daisuke Francis Nonaka, MD 1 and Amanda Arlene Fox, MD, MPH 1 Abstract The treatment strategy for ischemic mitral regurgitation (MR) continues to evolve with the completion of multicenter trials and the advancement of surgical and percutaneous interventional techniques. This review defines ischemic MR, outlines key clinical trials that assess surgical and interventional approaches, and reports the main elements of recent national guidelines for decision making in treatment of ischemic MR. New findings in percutaneous mitral valve repair and replacement for ischemic MR will also be described. Effective perioperative care of patients with ischemic MR requires clinicians to be well versed in the most up-to-date recommendations and emerging technological developments. Keywords ischemic mitral regurgitation, cardiac anesthesia, mitral valve repair, mitral valve replacement, cardiac surgery
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Ischemic Mitral Regurgitation: Repair, Replacement or NothingSeminars in Cardiothoracic and Vascular Anesthesia 2019, Vol. 23(1) 11 –19 © The Author(s) 2018 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1089253218792921 journals.sagepub.com/home/scv
Article
Background
The terms secondary, functional, and ischemic mitral regur- gitation (MR) are often used interchangeably as a means to differentiate from primary or degenerative MR, which is defined as regurgitation caused by pathology of the mitral valve (MV) leaflets and/or supporting chordae. In pure sec- ondary MR, the MV leaflets and chords are themselves normal;1 however, leaflet coaptation is hindered by struc- tural and functional abnormalities of the left ventricle.1,2 Furthermore, annular dilation and reduced systolic closing force by the ailing left ventricle contribute to malcoaptation and secondary MR.2,3 Table 1 summarizes the differences between primary and secondary MR.2 Ischemic MR is a subset of secondary MR in which the etiology of left ven- tricular dysfunction is a result of coronary artery disease and associated myocardial ischemia and infarction.1 Although ischemic MR will be the focus of this review, it is important to recognize that there are nonischemic causes of left ventricular dysfunction that can lead to secondary MR.
The 2014 American Heart Association/American College of Cardiology (AHA/ACC) Guideline for the Management of Patients With Valvular Heart Disease stratified secondary MR into 4 stages: at risk of MR (Stage A), progressive MR (Stage B; asymptomatic, nonsevere MR), asymptomatic severe MR (Stage C), and symptom- atic severe MR (Stage D).2 Stage D differs from stage C by the persistent symptoms of severe MR even after coronary revascularization and adherence to guideline-prescribed
medical therapy. It is noteworthy that in the 2014 guide- lines, stages C and D secondary MR (ie, severe MR) were defined by quantitative valve hemodynamic thresholds of effective regurgitant orifice area (EROA) 0.20 cm2, regurgitant volume 30 mL, and regurgitant fraction 50%. However, in the 2017 AHA/ACC Focused Update of the 2014 guidelines, the quantitative thresholds specify- ing severe secondary MR were redefined to match the val- ues of primary MR (EROA 0.40 cm2, regurgitant volume 60 mL, and regurgitant fraction 50%).4 Table 2 out- lines the differences between the 2014 and 2017 AHA/ ACC guidelines.2,4
The intent of the 2014 guidelines to define severe sec- ondary MR with lower hemodynamic thresholds compared with primary MR appears to have been driven by a couple of factors.5 First, studies such as ones by Rossi et al have shown worse outcomes in patients with severe secondary MR when defined as EROA 0.20 cm2 or regurgitant vol- ume 30 mL compared with those with EROA <0.20 cm2 or regurgitant volume <30 mL.6 Second, the echocardio- graphic technique of assessing proximal isovelocity surface area (PISA) has long been the traditional method to measure
792921 SCVXXX10.1177/1089253218792921Seminars in Cardiothoracic and Vascular AnesthesiaNonaka and Fox research-article2018
1University of Texas Southwestern Medical Center, Dallas, TX, USA
Corresponding Author: Daisuke F. Nonaka, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8894, USA. Email: [email protected]
Ischemic Mitral Regurgitation: Repair, Replacement or Nothing
Daisuke Francis Nonaka, MD1 and Amanda Arlene Fox, MD, MPH1
Abstract The treatment strategy for ischemic mitral regurgitation (MR) continues to evolve with the completion of multicenter trials and the advancement of surgical and percutaneous interventional techniques. This review defines ischemic MR, outlines key clinical trials that assess surgical and interventional approaches, and reports the main elements of recent national guidelines for decision making in treatment of ischemic MR. New findings in percutaneous mitral valve repair and replacement for ischemic MR will also be described. Effective perioperative care of patients with ischemic MR requires clinicians to be well versed in the most up-to-date recommendations and emerging technological developments.
Keywords ischemic mitral regurgitation, cardiac anesthesia, mitral valve repair, mitral valve replacement, cardiac surgery
12 Seminars in Cardiothoracic and Vascular Anesthesia 23(1)
EROA in MR. However, PISA underestimates EROA in secondary MR,7 because this method assumes the flow con- vergence base in MR is spherical. EROA is based on a PISA calculation of 2πr2, where r is the radius of the sphere. Research has revealed EROA in secondary MR is not spher- ical, but rather crescentic in shape by measuring the vena contracta area (VCA) using 3D echocardiography.7 Therefore, the PISA method’s inherent assumption of a spherical regurgitant orifice in patients with secondary MR results in an underestimation of the actual EROA. An addi- tional pitfall of the PISA technique for measuring EROA in secondary MR is its biphasic pattern.5 The VCA of second- ary MR actually peaks in both early and late systole, and reaches a nadir in mid-systole.8 This biphasic pattern is due to a disequilibrium between the MV closing force generated by left ventricular (LV) contraction and MV opening force from tethering by the papillary muscles, chords, and LV wall.9 LV contracting force and pressure is lower at early and late systole causing the tethering force to prevail and maintain a larger EROA than during mid-systole when LV pressure and MV closing forces are greater. Thus, an EROA calculated by the PISA method during mid-systole would also underestimate the area.
When the 2014 AHA/ACC guideline published lower hemodynamic thresholds for severe secondary MR, some questioned the approach as haphazardly adapting to a sys- tems-based error in the PISA calculation. It was noted that measuring VCA to obtain the EROA could easily avoid the underestimation problem.5 The 2017 focused update responded to this concern by aligning the hemodynamic definition for quantifying severe secondary and primary MR to the same values, with the 2017 update also stating that for secondary MR “effective regurgitant orifice cutoff of >0.2 cm2 is more sensitive and >0.4 cm2 is more spe- cific for severe MR.”4 The 2017 guideline update empha- sized the importance of taking an integrative approach by incorporating both clinical and echocardiographic assess- ments in the decision making process for assessing sever- ity and treatment of secondary MR.
Surgical Therapy
In 2016 the Cardiothoracic Surgical Trials Network (CTSN) published the results of 2 landmark multicenter randomized trials on the surgical treatment of moderate and severe isch- emic MR.10,11 The following section reviews these trials
Table 1. Summary of Mitral Regurgitation (MR) Type.
Descriptive Name Common Etiologies Treatment
Primary MR Degenerative MR Mitral valve prolapse, Barlow’s valve, fibroelastic deficiency disease, connective tissue disorder, infective endocarditis, rheumatic heart disease, cleft mitral leaflet, history of chest radiation
Predominantly surgical or percutaneous interventions
Secondary MR Functional MR Ischemic heart disease (coronary disease) or nonischemic cardiomyopathy resulting in left ventricular dysfunction, papillary muscle displacement, leaflet tethering, and annular dilation
Medical optimization followed by possible surgical or percutaneous interventions
Table 2. Comparison of the 2014 Versus 2017 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease for Secondary MR.
Stage Definition 2014 AHA/ACC Valve
Hemodynamics 2017 AHA/ACC Valve
Hemodynamics
A At risk of MR No MR jet or small central jet area <20% LA on Doppler
No MR jet or small central jet area <20% LA on Doppler
Small vena contracta <0.30 cm Small vena contracta <0.30 cm B Progressive MR ERO <0.20 cm2 ERO <0.40 cm2
Regurgitant volume <30 mL Regurgitant volume <60 mL Regurgitant fraction <50% Regurgitant fraction <50% C Asymptomatic severe MR ERO 0.20 cm2 ERO 0.40 cm2
Regurgitant volume 30 mL Regurgitant volume 60 mL Regurgitant fraction 50% Regurgitant fraction 50% D Symptomatic severe MR ERO 0.20 cm2 ERO 0.40 cm2
Regurgitant volume 30 mL Regurgitant volume 60 mL Regurgitant fraction 50% Regurgitant fraction 50%
Abbreviations: AHA/ACC, American Heart Association/American College of Cardiology; MR, mitral regurgitation; LA, left atrium; ERO, effective regurgitant orifice.
Nonaka and Fox 13
and updated guidelines including the class of recommenda- tion and level of evidence.
Severe Ischemic MR
The CTSN performed a multicenter trial with 22 institu- tions where 251 patients with severe ischemic MR were randomized to either surgical MV repair or replacement and followed for 2 years.10 The primary outcome of this study was left ventricular end systolic volume index (LVESVI) at 1 year to measure left ventricular remodel- ing, and the secondary outcomes were a composite of major adverse cardiac or cerebrovascular events, death, serious adverse events, MR recurrence, rehospitalization, and quality of life. The investigators found no significant difference in reverse remodeling as measured by decrease in LVESVI between the 2 study groups. There was also no significant difference in incidence of death (19.0% in repair group and 23.2% in replacement group; P = .42), overall composite of serious adverse events, or need for any hospital admissions at the end of 2 years. However, a subanalysis revealed that the MV repair group had more frequent serious adverse events associated with heart fail- ure and cardiovascular hospital admissions. The MV repair group had significantly higher recurrence of moderate and severe MR (58.8% in the repair group vs 3.8% in the replacement group; P < .001), which is what presumably resulted in the increased incidence of heart failure and car- diovascular hospital admissions. Within those who had MV repair and suffered moderate or severe MR recur- rence, 14% had severe MR, while none of the patients in the MV replacement group had severe MR. In addition, 66% of all patients in both MV repair and replacement groups who did not have MR recurrence were found to have a higher quality of life score by the Minnesota Living with Heart Failure Questionnaire.
An interesting finding was that individuals who received MV repair and who stayed free from moderate or severe recurrent MR ended up with significantly improved reverse remodeling as assessed by decrease in LVESVI compared with those who developed moderate or severe recurrent MR (LVESVI, 42.7 ± 26.4 without MR recurrence and 62.6 ± 26.9 with MR recurrence, P < .001). These finding were detected in an earlier 1-year interval analysis of this study.3 The CTSN investigators pursued further studies to deter- mine whether MR recurrence after MV repair could be pre- dicted prior to surgery, as this would allow better selection for MV repair to those patients most likely to benefit from a durable repair.12 The investigators thus assessed the 116 patients who had been randomized to the MV repair arm of the study and assessed their clinical and preoperative echo- cardiographic data to develop a multivariable model for pre- dicting failure of MV repair defined as recurrent moderate or severe MR and death 2 years after surgery. In total, 76 out of 116 patients had MR recurrence or death. This model had
an excellent balance between sensitivity and specificity, with a c-index of 0.82. The model included 10 variables for predicting recurrent MR after MV repair: age, body mass index, sex, race, EROA, basal aneurysm or dyskinesis, New York Heart Association class, history of coronary artery bypass grafting (CABG), percutaneous coronary interven- tion (PCI), and ventricular arrhythmias. Only basal aneu- rysm/dyskinesis was found to be an independent predictor of MR recurrence and/or death (P < .001). Preoperative echo parameters that quantified the degree of leaflet tether- ing such as leaflet angle, tenting height and area, and LV volumes were not independently predictive.
The American Association for Thoracic Surgery (AATS) included the findings of the CTSN severe isch- emic MR trial and the additional MV repair arm study pre- dicting MR recurrence in their most recent 2016 guideline on ischemic MR.1 The 2016 AATS guideline states with regard to MV replacement:
MV replacement is reasonable in patients with severe ischemic MR who remain symptomatic despite guideline- directed medical and cardiac device therapy (ie, stage D), and who have a basal aneurysm/dyskinesis, significant leaflet tethering, and/or severe left ventricular dilatation (end diastolic diameter > 6.5 cm); (class of recommendation IIa, level of evidence B).
This guideline also gives a statement for MV repair:
MV repair with an undersized complete rigid annuloplasty ring may be considered in patients with severe ischemic MR who remain symptomatic despite guideline-directed medical and cardiac device therapy (ie, stage D) and who do not have a basal aneurysm/dyskinesis, significant leaflet tethering, or severe LV enlargement (end diastolic dimension>6.5 cm); (class of recommendation IIb, level of evidence B).
The difference between the 2 recommendations is the class of recommendation in MV replacement is IIa, while for MV repair it is the weaker IIb. The guideline emphasizes MV repair should be considered when a patient is not at predicted high risk for MR recurrence and reiterates the strong predictive value of basal aneurysm or dyskinesis from the CTSN study.
The 2017 AHA/ACC valve guideline update differs from the 2016 AATS guideline by combining MV repair and replacement into one recommendation:
Mitral valve repair or replacement may be considered for severely symptomatic patients (New York Heart Association class III to IV) with chronic severe secondary MR (stage D) who have persistent symptoms despite optimal guideline- directed medical therapy for heart failure. (Class of recommendation IIb, level of evidence B).
This recommendation has a class of recommendation IIb and not IIa from its incorporation of MV repair with
14 Seminars in Cardiothoracic and Vascular Anesthesia 23(1)
replacement. To resolve the difference in strength of rec- ommendation between MV replacement and repair, the 2017 AHA/ACC guideline update follows with the subse- quent statement:
It is reasonable to choose chordal-sparing MV replacement over downsized annuloplasty repair if operation is considered for severely symptomatic patients (New York Heart Association class III to IV) with chronic severe ischemic MR (stage D) and persistent symptoms despite guideline-directed medical therapy for heart failure. (Class of recommendation IIa, level of evidence B–Randomized).
This statement’s class of recommendation IIa in the AHA/ ACC guideline aligns itself with the AATS guideline form- ing a consistent endorsement of the recommended deci- sion-making process for patients with severe ischemic MR.
The clinician must be aware of which patients are appropriate candidates for surgery. The advent of trans- catheter mitral valve procedures has led to the publica- tion by the Mitral Valve Academic Research Consortium of clinical trial design principles. The purpose of this consensus document is to encourage consistency in forth- coming transcatheter mitral valve trials to allow compari- son between different studies.13 This document defines patients who are at high or prohibitive risk (ie, end-stage MV disease) for surgery as Society of Thoracic Surgeons predicted risk of mortality 8% for MV replacement, frailty, major organ system compromise, “severe mitral annular calcification, the presence of a hostile chest, pat- ent left internal mammary artery bypass graft crossing the midline, prior tracheotomy, and severe pulmonary hypertension with or without right ventricular dysfunc- tion.” Although the intent of the above definition of high or prohibitive risk for MV surgery was created to assist clinicians in determining who is appropriate to consider for candidacy for transcatheter mitral valve procedure studies, it may also help clinicians identify those who are unsuitable for surgical therapy in general. The remaining options for these patients include mandatory medical therapy (“angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, beta blockers and/or aldo- sterone antagonists”)2 and consideration for cardiac resynchronization therapy, which synchronizes papillary muscle contraction to increase MV closing force, and thus reducing MR.14,15
In summary, it is reasonable for patients with severe secondary MR (with symptoms, stage D) and have an increased predicted risk for MR recurrence after potential MV repair, to have a MV replacement. If a patient has stage D secondary MR, but is absent of predictive factors for MR recurrence, then MV repair may be considered. Both recommendations advocate for optimization of medi- cal and cardiac device therapy prior to surgery.
Severe Ischemic MR in Patients Scheduled for Other Cardiac Surgery
For patients with severe ischemic MR who are scheduled to undergo other cardiac surgery such as CABG or aortic valve surgery, the 2017 AHA/ACC guideline recommends the following: “Mitral valve surgery is reasonable for patients with chronic severe secondary MR (stages C and D) who are undergoing CABG or aortic valve replace- ment. (Class of recommendation IIa, level of evidence C).” The 2016 AATS guideline does not comment on con- current MV surgery with another cardiac surgery for severe ischemic MR. Whether to perform MV repair or replacement depends on the predicted risk of MR recur- rence as reviewed in the above section. Table 3 outlines the recommendations by both the AATS and AHA/ACC for severe ischemic MR.1,4
Moderate Ischemic MR in Patients Scheduled for Other Cardiac Surgery
Isolated moderate ischemic MR is considered stage B dis- ease and the recommendation by the 2017 AHA/ACC guideline is for periodic monitoring.4 However, many patients undergoing CABG have associated ischemic MR, and the decision to perform MV surgery for these individ- uals has been long debated. The CTSN performed another multicenter trial, enrolling 301 patients scheduled for CABG surgery for multi-vessel coronary artery disease who also had moderate ischemic MR. Patients were ran- domized to CABG-only or CABG plus MV repair with a rigid or semirigid complete ring.11 After 2 years, they found no significant difference between groups with regard to reverse remodeling assessed by LVESVI or death. The 2 groups were also similar with regard to hospi- tal readmission, serious adverse events, and a composite of major adverse cardiac and cerebrovascular events. The groups differed in the residual or recurrent rate of moder- ate or severe MR at 2-year follow-up, with the CABG- only group more susceptible (32.3% vs 11.2% for the CABG plus MV repair group, P < .001). Despite this sig- nificantly increased incidence of moderate or severe MR in the CABG-only group, there was no detectable increase in adverse events including heart failure events (84.0 events per 100 patient-years for CABG-only vs 92.0 events per 100 patient-years for CABG plus MV repair, P = .35). Comparing patients with and without moderate or severe MR at 2 years found that persistent MR was associated with decreased reverse remodeling and less improvement in LVESVI.
In the aforementioned study, the CABG plus MV repair group did have a significantly increased rate of neurologi- cal events (14 events in CABG plus MV repair group vs 4
Nonaka and Fox 15
events in CABG-only group, P = .02) and supraventricu- lar arrhythmias (24 events in CABG plus MV repair group vs 11 events in CABG-only group, P = .04). All of these events occurred within the first year after surgery.11,16 The authors postulate that the increase in neurological events was related to longer cardiopulmonary bypass and cross- clamp times, the cardiotomy, and atrial incision increasing risk of thromboembolism. The authors speculate that the higher incidence of supraventricular arrhythmias in the CABG plus MV repair group was related to the left atrial approach and corresponding incision needed to perform the MV repair.
As with the outcome from the CTSN severe ischemic MR trial that compared the outcomes of MV repairs ver- sus replacements, both the 2016 AATS and 2017 AHA/ ACC guidelines incorporated the findings of the CTSN moderate ischemic MR trial into their respective updates.1,4 The 2016 AATS guideline states: “In patients with moderate ischemic MR undergoing CABG, MV repair with an undersized complete rigid annuloplasty ring may be considered (class of recommendation IIb, level of evidence B).” The 2017 AHA/ACC update also published a statement with a similar class of recommen- dation IIb, level of evidence B–Randomized, but the text of their recommendation is slightly ambiguous: “In patients with chronic, moderate, ischemic MR (stage B) undergoing CABG, the usefulness of mitral valve repair is
uncertain,” and emphasized the weak evidence for the utility of concurrent MV repair with CABG. Table 3 sum- marizes the AATS and AHA/ACC guideline recommen- dations for moderate ischemic MR.1,4
The 2016 AATS updated guidelines acknowledges the challenge surgeons face when operating on a patient for CABG with moderate MR. The update suggests consider- ing whether the patient’s major clinical complaint appears to be of cardiac (angina) or pulmonary (shortness of breath) origins. If the…
Article
Background
The terms secondary, functional, and ischemic mitral regur- gitation (MR) are often used interchangeably as a means to differentiate from primary or degenerative MR, which is defined as regurgitation caused by pathology of the mitral valve (MV) leaflets and/or supporting chordae. In pure sec- ondary MR, the MV leaflets and chords are themselves normal;1 however, leaflet coaptation is hindered by struc- tural and functional abnormalities of the left ventricle.1,2 Furthermore, annular dilation and reduced systolic closing force by the ailing left ventricle contribute to malcoaptation and secondary MR.2,3 Table 1 summarizes the differences between primary and secondary MR.2 Ischemic MR is a subset of secondary MR in which the etiology of left ven- tricular dysfunction is a result of coronary artery disease and associated myocardial ischemia and infarction.1 Although ischemic MR will be the focus of this review, it is important to recognize that there are nonischemic causes of left ventricular dysfunction that can lead to secondary MR.
The 2014 American Heart Association/American College of Cardiology (AHA/ACC) Guideline for the Management of Patients With Valvular Heart Disease stratified secondary MR into 4 stages: at risk of MR (Stage A), progressive MR (Stage B; asymptomatic, nonsevere MR), asymptomatic severe MR (Stage C), and symptom- atic severe MR (Stage D).2 Stage D differs from stage C by the persistent symptoms of severe MR even after coronary revascularization and adherence to guideline-prescribed
medical therapy. It is noteworthy that in the 2014 guide- lines, stages C and D secondary MR (ie, severe MR) were defined by quantitative valve hemodynamic thresholds of effective regurgitant orifice area (EROA) 0.20 cm2, regurgitant volume 30 mL, and regurgitant fraction 50%. However, in the 2017 AHA/ACC Focused Update of the 2014 guidelines, the quantitative thresholds specify- ing severe secondary MR were redefined to match the val- ues of primary MR (EROA 0.40 cm2, regurgitant volume 60 mL, and regurgitant fraction 50%).4 Table 2 out- lines the differences between the 2014 and 2017 AHA/ ACC guidelines.2,4
The intent of the 2014 guidelines to define severe sec- ondary MR with lower hemodynamic thresholds compared with primary MR appears to have been driven by a couple of factors.5 First, studies such as ones by Rossi et al have shown worse outcomes in patients with severe secondary MR when defined as EROA 0.20 cm2 or regurgitant vol- ume 30 mL compared with those with EROA <0.20 cm2 or regurgitant volume <30 mL.6 Second, the echocardio- graphic technique of assessing proximal isovelocity surface area (PISA) has long been the traditional method to measure
792921 SCVXXX10.1177/1089253218792921Seminars in Cardiothoracic and Vascular AnesthesiaNonaka and Fox research-article2018
1University of Texas Southwestern Medical Center, Dallas, TX, USA
Corresponding Author: Daisuke F. Nonaka, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8894, USA. Email: [email protected]
Ischemic Mitral Regurgitation: Repair, Replacement or Nothing
Daisuke Francis Nonaka, MD1 and Amanda Arlene Fox, MD, MPH1
Abstract The treatment strategy for ischemic mitral regurgitation (MR) continues to evolve with the completion of multicenter trials and the advancement of surgical and percutaneous interventional techniques. This review defines ischemic MR, outlines key clinical trials that assess surgical and interventional approaches, and reports the main elements of recent national guidelines for decision making in treatment of ischemic MR. New findings in percutaneous mitral valve repair and replacement for ischemic MR will also be described. Effective perioperative care of patients with ischemic MR requires clinicians to be well versed in the most up-to-date recommendations and emerging technological developments.
Keywords ischemic mitral regurgitation, cardiac anesthesia, mitral valve repair, mitral valve replacement, cardiac surgery
12 Seminars in Cardiothoracic and Vascular Anesthesia 23(1)
EROA in MR. However, PISA underestimates EROA in secondary MR,7 because this method assumes the flow con- vergence base in MR is spherical. EROA is based on a PISA calculation of 2πr2, where r is the radius of the sphere. Research has revealed EROA in secondary MR is not spher- ical, but rather crescentic in shape by measuring the vena contracta area (VCA) using 3D echocardiography.7 Therefore, the PISA method’s inherent assumption of a spherical regurgitant orifice in patients with secondary MR results in an underestimation of the actual EROA. An addi- tional pitfall of the PISA technique for measuring EROA in secondary MR is its biphasic pattern.5 The VCA of second- ary MR actually peaks in both early and late systole, and reaches a nadir in mid-systole.8 This biphasic pattern is due to a disequilibrium between the MV closing force generated by left ventricular (LV) contraction and MV opening force from tethering by the papillary muscles, chords, and LV wall.9 LV contracting force and pressure is lower at early and late systole causing the tethering force to prevail and maintain a larger EROA than during mid-systole when LV pressure and MV closing forces are greater. Thus, an EROA calculated by the PISA method during mid-systole would also underestimate the area.
When the 2014 AHA/ACC guideline published lower hemodynamic thresholds for severe secondary MR, some questioned the approach as haphazardly adapting to a sys- tems-based error in the PISA calculation. It was noted that measuring VCA to obtain the EROA could easily avoid the underestimation problem.5 The 2017 focused update responded to this concern by aligning the hemodynamic definition for quantifying severe secondary and primary MR to the same values, with the 2017 update also stating that for secondary MR “effective regurgitant orifice cutoff of >0.2 cm2 is more sensitive and >0.4 cm2 is more spe- cific for severe MR.”4 The 2017 guideline update empha- sized the importance of taking an integrative approach by incorporating both clinical and echocardiographic assess- ments in the decision making process for assessing sever- ity and treatment of secondary MR.
Surgical Therapy
In 2016 the Cardiothoracic Surgical Trials Network (CTSN) published the results of 2 landmark multicenter randomized trials on the surgical treatment of moderate and severe isch- emic MR.10,11 The following section reviews these trials
Table 1. Summary of Mitral Regurgitation (MR) Type.
Descriptive Name Common Etiologies Treatment
Primary MR Degenerative MR Mitral valve prolapse, Barlow’s valve, fibroelastic deficiency disease, connective tissue disorder, infective endocarditis, rheumatic heart disease, cleft mitral leaflet, history of chest radiation
Predominantly surgical or percutaneous interventions
Secondary MR Functional MR Ischemic heart disease (coronary disease) or nonischemic cardiomyopathy resulting in left ventricular dysfunction, papillary muscle displacement, leaflet tethering, and annular dilation
Medical optimization followed by possible surgical or percutaneous interventions
Table 2. Comparison of the 2014 Versus 2017 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease for Secondary MR.
Stage Definition 2014 AHA/ACC Valve
Hemodynamics 2017 AHA/ACC Valve
Hemodynamics
A At risk of MR No MR jet or small central jet area <20% LA on Doppler
No MR jet or small central jet area <20% LA on Doppler
Small vena contracta <0.30 cm Small vena contracta <0.30 cm B Progressive MR ERO <0.20 cm2 ERO <0.40 cm2
Regurgitant volume <30 mL Regurgitant volume <60 mL Regurgitant fraction <50% Regurgitant fraction <50% C Asymptomatic severe MR ERO 0.20 cm2 ERO 0.40 cm2
Regurgitant volume 30 mL Regurgitant volume 60 mL Regurgitant fraction 50% Regurgitant fraction 50% D Symptomatic severe MR ERO 0.20 cm2 ERO 0.40 cm2
Regurgitant volume 30 mL Regurgitant volume 60 mL Regurgitant fraction 50% Regurgitant fraction 50%
Abbreviations: AHA/ACC, American Heart Association/American College of Cardiology; MR, mitral regurgitation; LA, left atrium; ERO, effective regurgitant orifice.
Nonaka and Fox 13
and updated guidelines including the class of recommenda- tion and level of evidence.
Severe Ischemic MR
The CTSN performed a multicenter trial with 22 institu- tions where 251 patients with severe ischemic MR were randomized to either surgical MV repair or replacement and followed for 2 years.10 The primary outcome of this study was left ventricular end systolic volume index (LVESVI) at 1 year to measure left ventricular remodel- ing, and the secondary outcomes were a composite of major adverse cardiac or cerebrovascular events, death, serious adverse events, MR recurrence, rehospitalization, and quality of life. The investigators found no significant difference in reverse remodeling as measured by decrease in LVESVI between the 2 study groups. There was also no significant difference in incidence of death (19.0% in repair group and 23.2% in replacement group; P = .42), overall composite of serious adverse events, or need for any hospital admissions at the end of 2 years. However, a subanalysis revealed that the MV repair group had more frequent serious adverse events associated with heart fail- ure and cardiovascular hospital admissions. The MV repair group had significantly higher recurrence of moderate and severe MR (58.8% in the repair group vs 3.8% in the replacement group; P < .001), which is what presumably resulted in the increased incidence of heart failure and car- diovascular hospital admissions. Within those who had MV repair and suffered moderate or severe MR recur- rence, 14% had severe MR, while none of the patients in the MV replacement group had severe MR. In addition, 66% of all patients in both MV repair and replacement groups who did not have MR recurrence were found to have a higher quality of life score by the Minnesota Living with Heart Failure Questionnaire.
An interesting finding was that individuals who received MV repair and who stayed free from moderate or severe recurrent MR ended up with significantly improved reverse remodeling as assessed by decrease in LVESVI compared with those who developed moderate or severe recurrent MR (LVESVI, 42.7 ± 26.4 without MR recurrence and 62.6 ± 26.9 with MR recurrence, P < .001). These finding were detected in an earlier 1-year interval analysis of this study.3 The CTSN investigators pursued further studies to deter- mine whether MR recurrence after MV repair could be pre- dicted prior to surgery, as this would allow better selection for MV repair to those patients most likely to benefit from a durable repair.12 The investigators thus assessed the 116 patients who had been randomized to the MV repair arm of the study and assessed their clinical and preoperative echo- cardiographic data to develop a multivariable model for pre- dicting failure of MV repair defined as recurrent moderate or severe MR and death 2 years after surgery. In total, 76 out of 116 patients had MR recurrence or death. This model had
an excellent balance between sensitivity and specificity, with a c-index of 0.82. The model included 10 variables for predicting recurrent MR after MV repair: age, body mass index, sex, race, EROA, basal aneurysm or dyskinesis, New York Heart Association class, history of coronary artery bypass grafting (CABG), percutaneous coronary interven- tion (PCI), and ventricular arrhythmias. Only basal aneu- rysm/dyskinesis was found to be an independent predictor of MR recurrence and/or death (P < .001). Preoperative echo parameters that quantified the degree of leaflet tether- ing such as leaflet angle, tenting height and area, and LV volumes were not independently predictive.
The American Association for Thoracic Surgery (AATS) included the findings of the CTSN severe isch- emic MR trial and the additional MV repair arm study pre- dicting MR recurrence in their most recent 2016 guideline on ischemic MR.1 The 2016 AATS guideline states with regard to MV replacement:
MV replacement is reasonable in patients with severe ischemic MR who remain symptomatic despite guideline- directed medical and cardiac device therapy (ie, stage D), and who have a basal aneurysm/dyskinesis, significant leaflet tethering, and/or severe left ventricular dilatation (end diastolic diameter > 6.5 cm); (class of recommendation IIa, level of evidence B).
This guideline also gives a statement for MV repair:
MV repair with an undersized complete rigid annuloplasty ring may be considered in patients with severe ischemic MR who remain symptomatic despite guideline-directed medical and cardiac device therapy (ie, stage D) and who do not have a basal aneurysm/dyskinesis, significant leaflet tethering, or severe LV enlargement (end diastolic dimension>6.5 cm); (class of recommendation IIb, level of evidence B).
The difference between the 2 recommendations is the class of recommendation in MV replacement is IIa, while for MV repair it is the weaker IIb. The guideline emphasizes MV repair should be considered when a patient is not at predicted high risk for MR recurrence and reiterates the strong predictive value of basal aneurysm or dyskinesis from the CTSN study.
The 2017 AHA/ACC valve guideline update differs from the 2016 AATS guideline by combining MV repair and replacement into one recommendation:
Mitral valve repair or replacement may be considered for severely symptomatic patients (New York Heart Association class III to IV) with chronic severe secondary MR (stage D) who have persistent symptoms despite optimal guideline- directed medical therapy for heart failure. (Class of recommendation IIb, level of evidence B).
This recommendation has a class of recommendation IIb and not IIa from its incorporation of MV repair with
14 Seminars in Cardiothoracic and Vascular Anesthesia 23(1)
replacement. To resolve the difference in strength of rec- ommendation between MV replacement and repair, the 2017 AHA/ACC guideline update follows with the subse- quent statement:
It is reasonable to choose chordal-sparing MV replacement over downsized annuloplasty repair if operation is considered for severely symptomatic patients (New York Heart Association class III to IV) with chronic severe ischemic MR (stage D) and persistent symptoms despite guideline-directed medical therapy for heart failure. (Class of recommendation IIa, level of evidence B–Randomized).
This statement’s class of recommendation IIa in the AHA/ ACC guideline aligns itself with the AATS guideline form- ing a consistent endorsement of the recommended deci- sion-making process for patients with severe ischemic MR.
The clinician must be aware of which patients are appropriate candidates for surgery. The advent of trans- catheter mitral valve procedures has led to the publica- tion by the Mitral Valve Academic Research Consortium of clinical trial design principles. The purpose of this consensus document is to encourage consistency in forth- coming transcatheter mitral valve trials to allow compari- son between different studies.13 This document defines patients who are at high or prohibitive risk (ie, end-stage MV disease) for surgery as Society of Thoracic Surgeons predicted risk of mortality 8% for MV replacement, frailty, major organ system compromise, “severe mitral annular calcification, the presence of a hostile chest, pat- ent left internal mammary artery bypass graft crossing the midline, prior tracheotomy, and severe pulmonary hypertension with or without right ventricular dysfunc- tion.” Although the intent of the above definition of high or prohibitive risk for MV surgery was created to assist clinicians in determining who is appropriate to consider for candidacy for transcatheter mitral valve procedure studies, it may also help clinicians identify those who are unsuitable for surgical therapy in general. The remaining options for these patients include mandatory medical therapy (“angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, beta blockers and/or aldo- sterone antagonists”)2 and consideration for cardiac resynchronization therapy, which synchronizes papillary muscle contraction to increase MV closing force, and thus reducing MR.14,15
In summary, it is reasonable for patients with severe secondary MR (with symptoms, stage D) and have an increased predicted risk for MR recurrence after potential MV repair, to have a MV replacement. If a patient has stage D secondary MR, but is absent of predictive factors for MR recurrence, then MV repair may be considered. Both recommendations advocate for optimization of medi- cal and cardiac device therapy prior to surgery.
Severe Ischemic MR in Patients Scheduled for Other Cardiac Surgery
For patients with severe ischemic MR who are scheduled to undergo other cardiac surgery such as CABG or aortic valve surgery, the 2017 AHA/ACC guideline recommends the following: “Mitral valve surgery is reasonable for patients with chronic severe secondary MR (stages C and D) who are undergoing CABG or aortic valve replace- ment. (Class of recommendation IIa, level of evidence C).” The 2016 AATS guideline does not comment on con- current MV surgery with another cardiac surgery for severe ischemic MR. Whether to perform MV repair or replacement depends on the predicted risk of MR recur- rence as reviewed in the above section. Table 3 outlines the recommendations by both the AATS and AHA/ACC for severe ischemic MR.1,4
Moderate Ischemic MR in Patients Scheduled for Other Cardiac Surgery
Isolated moderate ischemic MR is considered stage B dis- ease and the recommendation by the 2017 AHA/ACC guideline is for periodic monitoring.4 However, many patients undergoing CABG have associated ischemic MR, and the decision to perform MV surgery for these individ- uals has been long debated. The CTSN performed another multicenter trial, enrolling 301 patients scheduled for CABG surgery for multi-vessel coronary artery disease who also had moderate ischemic MR. Patients were ran- domized to CABG-only or CABG plus MV repair with a rigid or semirigid complete ring.11 After 2 years, they found no significant difference between groups with regard to reverse remodeling assessed by LVESVI or death. The 2 groups were also similar with regard to hospi- tal readmission, serious adverse events, and a composite of major adverse cardiac and cerebrovascular events. The groups differed in the residual or recurrent rate of moder- ate or severe MR at 2-year follow-up, with the CABG- only group more susceptible (32.3% vs 11.2% for the CABG plus MV repair group, P < .001). Despite this sig- nificantly increased incidence of moderate or severe MR in the CABG-only group, there was no detectable increase in adverse events including heart failure events (84.0 events per 100 patient-years for CABG-only vs 92.0 events per 100 patient-years for CABG plus MV repair, P = .35). Comparing patients with and without moderate or severe MR at 2 years found that persistent MR was associated with decreased reverse remodeling and less improvement in LVESVI.
In the aforementioned study, the CABG plus MV repair group did have a significantly increased rate of neurologi- cal events (14 events in CABG plus MV repair group vs 4
Nonaka and Fox 15
events in CABG-only group, P = .02) and supraventricu- lar arrhythmias (24 events in CABG plus MV repair group vs 11 events in CABG-only group, P = .04). All of these events occurred within the first year after surgery.11,16 The authors postulate that the increase in neurological events was related to longer cardiopulmonary bypass and cross- clamp times, the cardiotomy, and atrial incision increasing risk of thromboembolism. The authors speculate that the higher incidence of supraventricular arrhythmias in the CABG plus MV repair group was related to the left atrial approach and corresponding incision needed to perform the MV repair.
As with the outcome from the CTSN severe ischemic MR trial that compared the outcomes of MV repairs ver- sus replacements, both the 2016 AATS and 2017 AHA/ ACC guidelines incorporated the findings of the CTSN moderate ischemic MR trial into their respective updates.1,4 The 2016 AATS guideline states: “In patients with moderate ischemic MR undergoing CABG, MV repair with an undersized complete rigid annuloplasty ring may be considered (class of recommendation IIb, level of evidence B).” The 2017 AHA/ACC update also published a statement with a similar class of recommen- dation IIb, level of evidence B–Randomized, but the text of their recommendation is slightly ambiguous: “In patients with chronic, moderate, ischemic MR (stage B) undergoing CABG, the usefulness of mitral valve repair is
uncertain,” and emphasized the weak evidence for the utility of concurrent MV repair with CABG. Table 3 sum- marizes the AATS and AHA/ACC guideline recommen- dations for moderate ischemic MR.1,4
The 2016 AATS updated guidelines acknowledges the challenge surgeons face when operating on a patient for CABG with moderate MR. The update suggests consider- ing whether the patient’s major clinical complaint appears to be of cardiac (angina) or pulmonary (shortness of breath) origins. If the…
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