December 18, 2020 via Mojtaba Chardoli
Post Peer Reviewed by:Reza Moazzeni, M.D. and Shahriar Lahouti, M.D.
- MV anatomy
- Mitral Regurgitation
- Differential diagnosis
- Bedside echocardiography in evaluation of severe MR in ED
- Going Further
Abbreviations: 2D, two-dimensional; ACC,American college of cardiology; ACS, acute coronary syndrome; AF, atrial fibrillation; ASE,American Society of Echocardiography; AV, aortic valve; AR, aortic regurgitation; AS, aortic stenosis; CM, cardiomyopathy; CWD, Continuous wave Doppler; CFD, color flow Doppler; EAE, European Association of Echocardiography; EF, ejection fraction; EROA, Effective regurgitant orifice area ;LA, left atrium; LAE, left atrial enlargement; LAP, left atrial pressure; LV, left ventricle; LVE, left ventricle enlargement ; LVOTO, left ventricular outflow tract obstruction; MV, mitral valve; MS, mitral stenosis; MR, mitral regurgitation; MVP, mitral valve prolapse; PAP, pulmonary arterial pressure; PH, pulmonary hypertension; POCUS, point of care ultrasound; PWD, pulse wave Doppler; RA, right atrium; RV, right ventricle; TTE, transthoracic echocardiography; TEE, transesophageal echocardiography; TV, tricuspid valve; TR, tricuspid regurgitation; VHD, valvular heart disease; VC, Vena contracta; VCA, Vena contracta area; VCW, Vena contracta width.
Introduction with a case
In a busy shift; a 45-year old woman with no significant past medical history presented to the hospital with acute onset of shortness of the breath and scattered cough (which she admits to cigarette smoking). Initial vitals BP140/95mm Hg, HR120, RR 28, SO2 91% room air. EKG was unremarkable. No fever, leg swelling or size discrepancy noticed. My enthusiastic resident put the patient on typical protocol for COPD exacerbation and gave a 500cc of bolus crystalloid as well. Two hours later her clinical condition deteriorated. She was sitting bolt upright, and looked pale and struggling for breath. Despite receiving oxygen and medications, her oxygen saturation trended down to 88%. What could have been done for this patient upon entry?
Patients who present with a clinical picture of cardiorespiratory failure require an expedited and precise assessment at the bedside. In such patients bedside echo is crucially important and can shift the diagnostic paradigm. Evaluation of the LV and RV systolic and diastolic function, heart rate and rhythm and preload are intertwined with valvular examination. Since the essence of POCUS is to expeditiously identify life threatening conditions, screening for valvular pathologies in the ED is mostly focused on identifying those valvular diseases which can put your patient’s life at risk. The purpose of these series of discussions is to review bedside echocardiographic evaluation of adult valvular emergencies in ED. At the end of the day, you should feel comfortable in evaluation of critical valvular lesions! 😀👏
Scope Of The Discussion
The major concern in ED is to rapidly identify life threatening valvular lesions. Three essential questions should be beared in mind when screening for valvular emergencies in ED:
- Is there a “severe” valvular dysfunction?
- Does this explain my patient’s clinical presentation?
- How has this finding changed my management plan?
In the following discussion, The MR is explored in detail.
Mitral Valve Apparatus
- Mitral annulus: A fibroelastic structure separating LA from LV (figure 1.C)
- Mitral leaflets: There are two thin leaflets. One is located anteriorly and is thicker and larger. The other is posteriorly located and is thinner & more flexible (figure 1.A,B)
- Comissures: Is the sites where the leaflets insert and joint to annulus (figure 2.A)
- Tendinous chords: Fibrous strings that attach specific portions of mitral leaflets to papillary muscle tips (figure 2.B,C). There are three types of chords based on the location of insertion:
- Primary (marginal): attaches at the leaflet tip. It’s primary function is to maintain coaptation of leaflets. Failure of the primary chords, either elongated which leads to leaflet prolapse, or primary chord rupture leading to flail leaflet are concerning.
- Secondary: attaches at mid-body of leaflets.
- Tertiary: attaches at base of leaflets and provides structural support.
- Papillary muscles (PM): Large trabeculated muscles that connect tendinous chords to the mitral leaflets (figure 3. A,B)
- Anterolateral PM (APM): The anatomic location is shown below. It receives dual blood supply (LAD & Cx) and therefore is relatively resistant to ischemia.
- Posteromedial PM (PPM): It receives single blood supply (either RCA or LCX) and is prone to injury from ischemia.
- Coaptation: Denotes how well the leaflets come together and touch each other. In healthy state, the leaflets nicely coapts and there’s no gap between them during systole. Coaptation zone on the leaflet surface shown below (figure 4). Poor coaptation results in regurgitation.
- Excursion: Denotes how smoothly and freely leaflets open up well during diastole. Poor excursion can be seen in stenotic valvular lesions.
- MV billowing: In normal MV, the leaflet tips meet each other (coaptation zone) beyond the annular plane (figure 5.A). Billowing MV is defined when a part of the MV body protrude into the LA (figure 5.B).
- MVP: Prolapse is defined as a severe billowing of the MV (≧ 2mm) into the LA (figure 5.C). It can occur in one or both leaflets (figure 5.D).
- Flail valve: It occurs when the leaflet edge protrudes into the LA (figure 5.E). Most commonly it is due to rupture of marginal chord, so that the leaflet tip is no longer being supported and it freely moves into the LA during systole. Presence of a flail valve always denotes a severe regurgitation. Papillary muscle rupture is an extreme form of flail valve wherein both leaflet tip and papillary muscle move freely into the LA during systole.
Leaflet Tethering: In a Normal MV, the leaflets tip come into close contact during systole. As mentioned earlier, the leaflets are supported by tendinous chords and papillary muscles (figure 6.A). When LV remodeling happens (e.g. after MI), the LV geometry is altered which results in displacement of papillary muscles. This will put excessive force on the corresponding leaflet (tethers the leaflet) and prevent complete closure (mal-coaptation) of MV during systole (figure 6.B). Depending on the involved etiology, tethering can be asymmetric (figure 6.C) as following ‘MI’ 5 or symmetric (figure 6.D) as in global LV remodeling secondary to ‘dilated CM’.
Definition: MR is defined as blood regurgitation from LV to LA during systole due to poor coaptation of the MV leaflets.
Clinical presentation: The clinical presentation of MR is variable. Development of signs and symptoms depends on multiple factors including mechanism and etiology, course of the disease (rate of progression), “severity” of MR, hemodynamic impact of MR and presence of other coexisting cardiac disease.
By enlarge, clinical presentation ranges from asymptomatic patients to those with exercise intolerance and in severe cases full blown pulmonary edema and cardiogenic shock. Other symptoms such as thromboembolism, hemoptysis, and right-sided heart failure do occur, but are less common than with mitral stenosis. However, there is an increased risk of infective endocarditis in patients with moderate to severe MR.
Clinical question #1: Let’s say that you have a patient who complains of acute dyspnea and POCUS reveals MR. Does this finding explain your patient’s symptom?🤔 Let’s walk through and define each piece of the puzzle which you need to answer this key question.
Mechanism of MR: Identification of the MR mechanism is important and has therapeutic implication. Since the MV is an active valve (in contrast to aortic valve, which is passive) with aforementioned muscles and chords originating from the left ventricle and supporting mitral leaflets, the dysfunction of the mitral valve can happen either primarily due to intrinsic valve pathology or secondary to left ventricular disease. Defining the mechanism of MR6 involves explaining how MV dysfunction has happened. Accordingly MR is classified as (figure 7):
- Primary (organic): Intrinsic leaflet pathology is the culprit mechanism of poor coaptation. Primary MR is suggested in 2D echo by visualizing: 👁🗨
- Presence of leaflet thickening, calcification, prolapse or flail
- Preserved annulus dynamic function
- Absence of tethering pattern
- Secondary (functional): A non-valvular heart disease (e.g. cardiomyopathy etc.) can primarily alter LV geometry (LV dilation) via remodeling process.This causes displacement of papillary muscles with resulting an imbalance between closure and tethering force on the MV as well as dilatation of the MV annulus7. Secondary MR is suggested in 2D echo by the presence of the following findings:
- Absent or mild leaflet thickening, calcification, prolapse of flail
- Impaired or even absence of annulus dynamic function
- Presence of tethering pattern (figure 6)
👉Patients with primary MR become symptomatic late in the course of the disease.
👉Primary and secondary MR may coexist.
💌Bonus: The definition of MV prolapse is explored earlier. Prolapse of the MV can be due to a variety of
etiologies classified as primary or secondary:
- Primary MVP: Is the most common cause of primary MR. Primary MVP is a myxomatous degenerative disease which involves the MV leaflets either in focal or diffuse fashion.
- Focal disease: In the focal form, there’s fibroelastic deficiency which results in focal and segmental leaflet thinning. Frequent associated findings include chordal rupture and mild annular enlargement.
- Diffuse (Barlow’s disease): This results in diffuse thickening with redundant leaflets. Associated findings include chordal elongation and rupture and severe annular dilation.
- Secondary MVP: Valve prolapse can happen following myocardial infarction, acute rheumatic fever, hypertrophic CM, annular calcification.
👉Primary AF can cause annular dilation, contributing to development of functional MR.8
Etiology of MR: Always consider what possible pathologic process (e.g. Infectious, inflammatory, ischemic, degenerative) could be involved in development of MR.
👉Some etiologies of MR are concerning as they can cause acute severe MR, resulting in cardiogenic shock. The etiology of acute and chronic MR is briefed below (figure 8).
👉Spontaneous rupture of the tendinous chord has been reported in several studies9 as well!
Severity of MR: The essential component of bedside evaluation of VHD in ED is to determine the severity of the disease (more on this below). Patient’s tolerance to MR is contingent upon acuteness of the process and severity of the MR among the list. Acute Severe MR is Not tolerable and development of acute pulmonary edema and,or cardiogenic shock is inevitable.
👉Patients with pre-existing systolic heart failure are more prone to become unstable by even a less severe degree of acute MR (i.e. moderate MR).
Course of the disease and rate of progression:
An acute severe MR is a devastating illness. On the other hand chronic MR often progresses through a time course. Patients with compensated chronic MR are mildly symptomatic, while those with decompensated chronic MR present with pulmonary edema. There’s a stage in between among patients with chronic MR, which is called transitional stage. Such patients greatly benefit from possible corrective operation before their cardiac geometry becomes severely altered.
💌Bonus: The natural history of degenerative primary MVP is often benign and complications (e.g. sudden cardiac death, endocarditis, requirement for surgery, cerebrovascular accident) rarely develop.
Hemodynamic impact of MR: The burden of MR on the heart is volume overload.
- In Acute Severe MR, this surplus of volume within LA, builds up a high pressure and therefore LAP is acutely increased, leading to development of acute pulmonary edema and cardiogenic shock.
- In Chronic MR, cardiac remodeling takes place over time as a compensatory mechanism in response to chronic volume overload and LAE, LVE develop. The more severe the MR, the more severe LV geometry alteration would be. While during earlier stages of chronic MR, the remodeling process is accommodative and patients remain asymptomatic (at the expense of left-chambers dilation), later on during advanced stages of chronic MR, the high build-up of pressure within the enlarged chambers puts patient at risk of developing acute pulmonary edema and cardiogenic shock following a clinical trigger.
👉In Chronic Primary MR, presence of the following factors imply Severity of the MR:
- LAE, LVE
- PH (type 2)
Presence of other cardiovascular disease: Presence of preexisting cardiopulmonary disorders have great impact on patient’s tolerance to mitral regurgitation. Patients with poor physiologic reserve or those with systolic dysfunction of the heart cannot tolerate even a moderate degree of new MR and clinical deterioration happens.
Patients with MR present with varying degrees of signs and symptoms of heart failure. Acute heart failure syndrome (AHFS) is synonymous with pulmonary edema in ED and most commonly manifests with shortness of the breath. AHFS has different hemodynamic phenotypes (figure 9).
Having different phenotypes with a myriad of etiologies make AHFS a challenging condition as the treatment is different for each corresponding etiology. The DDx of dyspnea and cardiogenic shock 10 is mentioned below. (figure 10). Despite this long list of differentials, POCUS is your friend 😘and can significantly help you to identify the culprit etiology and manage your patient appropriately.
Acute life threatening VHD is often overlooked in clinical practice because the clinical history may mimic other disease entities such as acute pulmonary process (e.g. pneumonia, ARDS).
Physicians should include acute valvular disease in the differential diagnosis of any patient presenting with cardiopulmonary decompensation and consider bedside echocardiography promptly to exclude or confirm this possibility.
Bedside echocardiography in evaluation of severe MR in ED
Scope of the examination: There are several qualitative and quantitative methods for comprehensive assessment of valvular dysfunction (guidelines from ASE 11 and EAE12 ), however these require both time and expertise. Moreover it is claimed that a comprehensive exam (quantitative assessment) rarely adds to the acute management of a severe valvular dysfunction that is readily apparent by a qualitative assessment13. The best approach to diagnose severe native valve failure in the ED is ‘practical, simple’ and incorporates 2D, CFD and PWD echocardiography which is explored below.
2D exam: It is your first tool. Try to obtain a focused window of the interested valve (MV) in multiple views and catch the possible valvular pathologies by eyeball 👁🗨. In 2D examination the following pathologies can be discerned:
- Leaflets: Pay specific attention and look for:
- Morphology: Leaflet thickening, calcifications, vegetation?
- Leaflets Motion: Valve coaptation, Prolapse, flail, restriction, leaflet tethering?
- Annulus: Size, dilation, motion
👉Other echocardiographic data which can be discerned in 2D: LV and RV size, function, and hypertrophy, Left and right atrial size. This information as explored earlier can help you to solve more pieces of your puzzle.
CFD assessment: It is the most essential part of examination for any suspected valvular lesions (especially regurgitation). However clinicians must be aware of important considerations and common pitfalls when using this mode. Understanding key concepts, such as Nyquist limit, and aliasing (figure.11) are requisite starting points before using CFD.
The following recommendations can help optimize the performance and accuracy when assessing regurgitation with CFD:
- Minimize imaging depth
- Narrow image sector size
- Set color gain appropriately: Use gain bottom to adjust the gain. Turn gain down; If you have too much color outside of the vessel, or too much aliasing. Turn up that color gain to get random speckles. When you see speckles, turn it down until speckles disappear.
- Align the imaging plane to be parallel with blood flow
- Set the Nyquist limit to 40–70 cm/s
- Use the smallest color box that reasonably includes the valve and receiving chamber of interest
The effect of color gain, Nyquisit time, and transducer frequency on color jet area is shown below (figure.12)
CFD identifies the presence of the regurgitant flow as well as its direction and provides valuable information regarding severity of regurgitation. In evaluating severity of the MR by CDF, always evaluate the three components of the jet (Jet area, VC, flow convergence; shown in figure 13) and the direction of the MR (central, eccentric, multiple jets in unpredictable directions).
Presence of regurgitant flow: CFD is able to directly display the high velocity backflow of blood into the LA in the form of a jet. The dominant color of the jet corresponds to the direction of flow (BART, standing for Blue away and Red toward the transducer). As velocities in such jets exceed the Nyquist limit and because of turbulent flow, there will also be an array of other colors in the jet. It is this aliased flow that makes jets easily visible.The various components of a regurgitant jet are described below (figure 14).
👉Flow convergence zone: It is the zone of increased flow velocity before the regurgitant orifice just like the swirls of water one sees in a bathtub close to the outlet. The velocity of flow increases towards the regurgitant orifice in concentric shells, causing a more or less semicircular region of aliased flow. The size of this region corresponds to the magnitude of blood flow and the size of the regurgitant orifice. Thus, it can be used to quantify the severity of regurgitation. The actual measurement of this area is somehow difficult, but one can make a crude estimate of this zone as:
- Absence of flow convergence zone: Implies mild MR
- Visible but small (<4 mm) flow convergence zone: Moderate MR
- Large (>1.0 cm) flow convergence zone: Suggests severe MR
👉Vena contracta (VC): It corresponds to the region in which blood passes through the valve. Velocity is highest here. The width of the vena contracta is a good marker of the severity of MR because it corresponds to the diameter of the regurgitant orifice area. The vena contracta width (VCW) is measured perpendicular to the color flow jet in the neck between the proximal flow convergence (PFC) and distal jet expansion.
- VCW ≧ 0.7cm indicates severe MR
- VCW <0.3cm indicates mild MR
VCW is a measurement largely independent of driving pressures and flow rates for a fixed orifices however, its accuracy with multiple jets is uncertain.
👉Jet body: The portion of the jet that is seen in the receiving chamber (LA) is the jet body. Its size also corresponds to the severity of MR. The jet area (the area that the jet body captures in the receiving chamber; the LA) can be estimated roughly by eyeball although assessment of the jet area is dependent on several variables (figure 15) and is not highly accurate. A large central jet (occupying >50% of the LA) can suggest severe MR.
👉Direction of the regurgitant flow: The jet body is directed into the receiving chamber (LA) in one of the following patterns. Identifying the direction of the jet not only can assess severity, but also can give you a hint regarding possible mechanism and etiology of MR.
- Centrally directed jet: often seen in MR associated with global LV dysfunction (functional MR).
- Eccentric jet: The jet body is directed towards the left atrial walls. Presence of an eccentric jet (of variable size) is a more accurate measure for defining severity of MR than jet area.
👉An eccentric jet suggests severe MR with high probability.
- Multiple jets in unpredictable directions: often is seen in endocarditis.
PWD assessment: Pulsed Doppler of pulmonary venous flow is a useful adjunct to evaluating the hemodynamic consequences of MR. The normal Doppler tracing of pulmonary venous flow shows dominant systolic components (figure 17). With increasing severity of MR, there is reduced systolic velocity and in severe MR systolic flow reversal is seen (more on this here)The limitation of this technique is mentioned in the table below (figure 18).
Bottom line: Since each echocardiographic parameter has its own advantages and limitations, try to evaluate and determine severity of MR by multiple methods. The following table (figure 18) summarizes the usefulness and limitations of each method.
Clinical question #2: I have performed POCUS in my critically ill patient and other diagnostic possibilities are less likely. Valvular dysfunction is on top of my differential diagnosis list. Is this a severe MR?
In the presence of ≧4 following strong parameters, MR is defined as severe and no further sophisticated and time consuming quantitative assessment is warranted.😀
- In 2D echo: Specific valvular lesions with high positive predictive value for a severe MR include any of the following: Flail leaflet, ruptured papillary muscle (figure 19), severe retraction, large perforation and tethering leaflet.
- Keep in mind that these findings are highly specific but their absence does not exclude presence of severe MR.
- In CFD: presence of the following findings are specific for a severe MR:
- VCW ≧ 0.7cm
- Flow convergence: Large flow convergence present throughout systole
- Jet area: An eccentric jet adhering, swirling and reaching posterior wall of the LA or a Large central jet occupying > 50% of the LA
- In PWD: Pulmonary vein flow tracing of systolic flow reversal pattern
Figure 19. Severe MR, Ruptured papillary muscle
In the presence of ≧4 following strong parameters, MR is defined mild and no further quantitative assessment is needed 😀
- 2D: Presence of following finding are valuable:
- Normal or mild leaflet abnormality (Mild thickening, calcification, or prolapse)
- Color flow jet area is small, central, narrow, often brief
- Flow convergence: Not visible, transient of small
- VC <0.3
- Mitral inflow: A-wave dominant
- PWD: Pulmonary vein flow tracing of systolic dominance pattern (may be blunted in LV dysfunction or AF)
👉If 2-3 criteria for either mild or severe MR were met, then it’s “probably” moderate and further quantitative assessment is required which are beyond the scope of our discussion.
👉Keep in mind that in the absence of coexisting cardiopulmonary disease, a mild-moderate valvular dysfunction is Not often the main problem of your critical patient. Look for other possible diagnoses!
The case revisited: Perform POCUS for any patients with signs and symptoms of cardiorespiratory dysfunction and do not attribute shortness of the breath to common diagnosis such as COPD exacerbation or pneumonia despite presence of clinical risk factors. In this case, POCUS (figure below) showed flail anterior MV. A flail leaflet in 2D is a concerning finding for severe MR. Lung US showed bilateral B-profile.
Management: General Strategy in ED
Clinical question #3: How has my management plan been changed by identifying a severe MR?
Acute severe MR with low blood pressure (cold and wet16):
- Oxygenation: Patients in cardiogenic shock often respond to BiPAP. It has been shown in several studies that BiPAP reduces intubation and mortality. It also reduces cardiac preload and afterload which are deserved in severe MR. Put your patient acutely on BiPAP and titrate up the pressure as tolerated. The possible up-titration of pressure is exemplified as:
- Start: iPAP 10 cmH2O / ePAP 5 cmH2O
- Increase: iPAP 15 cmH2O / ePAP 10 cmH2O
- Increase: iPAP 18 cmH2O / ePAP 14 cmH2O
Intubation: Intubation in cardiogenic shock has high risk of hypotension and cardiac arrest. If you’re in doubt about the need for intubation, initiate BiPAP and resuscitate before intubation.
- Protect MAP: Hypotension requires prompt treatment to defend the coronary and end-organ perfusion.
- Norepinephrine: Although it can improve the BP, it carries the risk that excessive afterload will increase the regurgitant flow back into the LA and worsens pulmonary edema.
- Low dose epinephrine (e.g <8mcg/min): it works predominantly as an inotrope. However, unlike dobutamine, epinephrine doesn’t cause vasodilation and hypotension. The net effect of low-dose epinephrine is often an improvement in blood pressure and cardiac output, without affecting systemic vascular resistance much.
- Pure inotrop (e.g dobutamine): If a patient does not respond to the above tier of treatments, it may be used for patients with reduced ejection fraction and refractory cardiogenic shock.
- Dysrhythmias: Patient with cardiogenic shock does not tolerate arrhythmias. AF may need to be terminated by cardioversion. Digoxin can be considered. It has inotropic properties, though with intravenous loading, improvement may occur over several hours!
Acute severe MR with normal blood pressure (Warm and wet):
- Oxygenation: The same rules are applied here as mentioned above.
- Reduce preload and afterload: Afterload reduction reduces regurgitant flow into the LA, and improves cardiac output. In the acute phase, a high-dose nitroglycerine infusion is the safest vasodilator. High doses (up to 250 mcg/min) may be needed to achieve arterial vasodilation, titrated against the patient’s blood pressure.
- Dysrhythmias: Try to terminate dysrhythmia.
👉Involve Cardiothoracic Surgery early in patients with severe valvular disease.
👉Consult Interventional Cardiology for possible intra-aortic balloon pump in patients with acute severe MR as a temporizing measure.
- ACS: Patients with acute MR due to ACS will benefit from revascularization. This may be sufficient to reverse acute MR, with the exception of MR caused by tendinous chord/papillary muscle rupture. Consult Interventional cardiology early for possible left heart catheterization and revascularization if indicated and possible 17 18.
- Endocarditis: Patients with acute MR due to endocarditis require broad-spectrum antibiotic treatment. Operative intervention may be required as well19.
Acute decompensation of chronic MR
While the same principle of management as mentioned above would be applied here, pay attention and try to Identify and correct possible clinical factors that may have triggered decompensation of chronic MR.
- Factors that can trigger acute decompensation of chronic MR include:
- New onset arrhythmia such as AF
- Decompensated coexisting condition such as pulmonary hypertension: These patients benefit from inhaled pulmonary vasodilators.
- Volume overload
- New insult to myocardial systolic performance such as AMI
Silverman NH. Echocardiography of congenital mitral valve disorders: echocardiographic-morphological comparisons. Cardiol Young. 2014 Dec;24(6):1030-48. doi: 10.1017/S1047951114002157. PMID: 25647377.
Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, Weissman NJ. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2017 Apr;30(4):303-371. doi: 10.1016/j.echo.2017.01.007. Epub 2017 Mar 14. PMID: 28314623.
Lancellotti P, Tribouilloy C, Hagendorff A, Popescu BA, Edvardsen T, Pierard LA, Badano L, Zamorano JL; Scientific Document Committee of the European Association of Cardiovascular Imaging. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2013 Jul;14(7):611-44. doi: 10.1093/ehjci/jet105. Epub 2013 Jun 3. PMID: 23733442.
Lancellotti P, Moura L, Pierard LA, Agricola E, Popescu BA, Tribouilloy C, Hagendorff A, Monin JL, Badano L, Zamorano JL; European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echocardiogr. 2010 May;11(4):307-32. doi: 10.1093/ejechocard/jeq031. PMID: 20435783
American Association For Thoracic Surgery Ischemic Mitral Regurgitation Consensus Guidelines Writing Committee, Kron IL, LaPar DJ, Acker MA, Adams DH, Ailawadi G, Bolling SF, Hung JW, Lim DS, Mack MJ, O’Gara PT, Parides MK, Puskas JD. 2016 update to The American Association for Thoracic Surgery consensus guidelines: Ischemic mitral valve regurgitation. J Thorac Cardiovasc Surg. 2017 May;153(5):1076-1079. doi: 10.1016/j.jtcvs.2016.11.068. Epub 2017 Jan 17. PMID: 28190606.
Dal-Bianco JP, Beaudoin J, Handschumacher MD, Levine RA. Basic mechanisms of mitral regurgitation. Can J Cardiol. 2014;30(9):971-981. doi:10.1016/j.cjca.2014.06.022
Silbiger JJ. Mechanistic insights into atrial functional mitral regurgitation: Far more complicated than just left atrial remodeling. Echocardiography. 2019 Jan;36(1):164-169. doi: 10.1111/echo.14249. PMID: 30620100
Gertz ZM, Raina A, Saghy L, Zado ES, Callans DJ, Marchlinski FE, Keane MG, Silvestry FE. Evidence of atrial functional mitral regurgitation due to atrial fibrillation: reversal with arrhythmia control. J Am Coll Cardiol. 2011 Sep 27;58(14):1474-81. doi: 10.1016/j.jacc.2011.06.032. PMID: 21939832.
Gabbay U, Yosefy C. The underlying causes of chordae tendinae rupture: a systematic review. Int J Cardiol. 2010 Aug 20;143(2):113-8. doi: 10.1016/j.ijcard.2010.02.011. Epub 2010 Mar 7. PMID: 20207434
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891-975. doi: 10.1002/ejhf.592. Epub 2016 May 20. PMID: 27207191
Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, Horton K, Ogunyankin KO, Palma RA, Velazquez EJ. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2019 Jan;32(1):1-64. doi: 10.1016/j.echo.2018.06.004. Epub 2018 Oct 1. PMID: 30282592
Lancellotti P, Price S, Edvardsen T, Cosyns B, Neskovic AN, Dulgheru R, Flachskampf FA, Hassager C, Pasquet A, Gargani L, Galderisi M, Cardim N, Haugaa KH, Ancion A, Zamorano JL, Donal E, Bueno H, Habib G. The use of echocardiography in acute cardiovascular care: recommendations of the European Association of Cardiovascular Imaging and the Acute Cardiovascular Care Association. Eur Heart J Acute Cardiovasc Care. 2015 Feb;4(1):3-5. doi: 10.1177/2048872614568073. Epub 2015 Jan 29. PMID: 25635106
Stout KK, Verrier ED. Acute valvular regurgitation. Circulation. 2009 Jun 30;119(25):3232-41. doi: 10.1161/CIRCULATIONAHA.108.782292. PMID: 19564568
Thiele H, Ohman EM, Desch S, Eitel I, de Waha S. Management of cardiogenic shock. Eur Heart J. 2015 May 21;36(20):1223-30. doi: 10.1093/eurheartj/ehv051. Epub 2015 Mar 1. PMID: 25732762
van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Mission: Lifeline. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017 Oct 17;136(16):e232-e268. doi: 10.1161/CIR.0000000000000525. Epub 2017 Sep 18. PMID: 28923988
Baran DA, Grines CL, Bailey S, Burkhoff D, Hall SA, Henry TD, Hollenberg SM, Kapur NK, O’Neill W, Ornato JP, Stelling K, Thiele H, van Diepen S, Naidu SS. SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheter Cardiovasc Interv. 2019 Jul 1;94(1):29-37. doi: 10.1002/ccd.28329. Epub 2019 May 19. PMID: 31104355
Rab T, Ratanapo S, Kern KB, Basir MB, McDaniel M, Meraj P, King SB 3rd, O’Neill W. Cardiac Shock Care Centers: JACC Review Topic of the Week. J Am Coll Cardiol. 2018 Oct 16;72(16):1972-1980. doi: 10.1016/j.jacc.2018.07.074. Erratum in: J Am Coll Cardiol. 2018 Nov 27;72(21):2685. PMID: 30309475
Truesdell AG, Tehrani B, Singh R, et al. ‘Combat’ Approach to Cardiogenic Shock. Interv Cardiol. 2018;13(2):81-86. doi:10.15420/icr.2017:35:3
Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, Dulgheru R, El Khoury G, Erba PA, Iung B, Miro JM, Mulder BJ, Plonska-Gosciniak E, Price S, Roos-Hesselink J, Snygg-Martin U, Thuny F, Tornos Mas P, Vilacosta I, Zamorano JL; ESC Scientific Document Group. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015 Nov 21;36(44):3075-3128. doi: 10.1093/eurheartj/ehv319. Epub 2015 Aug 29. PMID: 26320109