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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 28  |  Issue : 4  |  Page : 207-217

Mitral prolapse: An old mysterious entity – The incremental role of multimodality imaging in sports eligibility


1 Luigi Vanvitelli University, Monaldi Hospital, AORN Ospedali Dei Colli, Naples, Italy
2 Rummo Hospital, Benevento, Italy
3 Department of Advanced Biomedical Sciences, Federico Ii University of Naples, Naples, Italy

Date of Web Publication24-Dec-2018

Correspondence Address:
Antonello D’Andrea
Corso Vittorio Emanuele 121A, 80121, Naples
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcecho.jcecho_42_18

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  Abstract 


Mitral valve prolapse is generally a benign condition characterized by fibromyxomatous changes of the mitral leaflet with displacement into the left atrium and late-systolic regurgitation. Although it is an old clinical entity, it still arouses perplexity in diagnosis and clinical management. Complications, such as mitral regurgitation (MR), atrial fibrillation, congestive heart failure, endocarditis, ventricular arrhythmias, and sudden cardiac death (SCD), have been reported. A large proportion of the overall causes of SCD in young competitive athletes is explained by mitral valve prolapse. Recent studies have shown the fibrosis of the papillary muscles and inferobasal left ventricular wall in mitral valve prolapse, suggesting a possible origin of ventricular fatal arrhythmias. Athletes with mitral valve prolapse and MR should undergo annual evaluations including physical examination, echocardiogram, and exercise stress testing to evaluate the cardiovascular risks of competitive sports and obtain the eligibility. In this setting, multimodality imaging techniques – echocardiography, cardiac magnetic resonance, and cardiac computed tomography – should provide a broad spectrum of information, from diagnosis to clinical management of the major clinical profiles of the disease.

Keywords: Athletes, cardiac magnetic resonance, echocardiography, mitral valve prolapse, sport eligibility


How to cite this article:
Carbone A, D’Andrea A, Scognamiglio G, Scarafile R, Tocci G, Sperlongano S, Martone F, Radmilovic J, D’Amato M, Liccardo B, Scherillo M, Galderisi M, Golino P. Mitral prolapse: An old mysterious entity – The incremental role of multimodality imaging in sports eligibility. J Cardiovasc Echography 2018;28:207-17

How to cite this URL:
Carbone A, D’Andrea A, Scognamiglio G, Scarafile R, Tocci G, Sperlongano S, Martone F, Radmilovic J, D’Amato M, Liccardo B, Scherillo M, Galderisi M, Golino P. Mitral prolapse: An old mysterious entity – The incremental role of multimodality imaging in sports eligibility. J Cardiovasc Echography [serial online] 2018 [cited 2019 Sep 17];28:207-17. Available from: http://www.jcecho.org/text.asp?2018/28/4/207/248410




  Introduction Top


Mitral valve prolapse (MVP) was first identified, as a pathological entity, in the 1960s when the mid-systolic click and the late-systolic murmur were correlated with the demonstration of angiographic protrusion of the mitral leaflets into the left atrium (LA) and late-systolic regurgitation.[1] The cause of this anomalies remains controversial, and many theories have been proposed. Although MVP is generally a benign condition, the outcome is widely heterogeneous, and complications, such as mitral regurgitation (MR), atrial fibrillation, congestive heart failure (CHF), endocarditis, ventricular arrhythmias, and sudden cardiac death (SCD), have been reported.[2],[3],[4] Particularly, MVP has been reported to explain for a large proportion (as high as 11%) of the overall causes of SCD in young competitive athletes.[4] In this review, we summarize our current knowledge of the diagnosis, pathophysiology, genetics, epidemiology, and prognosis and MVP, with a focus on potential implications in sports eligibility.


  Mitral Valve Prolapse: A single Definition? Top


MVP is present in approximately 4% of the general population and is most prevalent in young women.[5] MVP is a clinical entity characterized by typical fibromyxomatous changes in the mitral leaflet tissue with superior displacement of one or both leaflets into the LA.[3],[6] Barlow entered in the international cardiology scene in 1963, with his observations on the mid-systolic click and late-systolic murmur associated with billowing of the mitral valve (MV) leaflets and MR, which was subsequently known as the Barlow syndrome.[7] Barlow never liked using the term “prolapse” and preferred the term “billowing” of the mitral leaflet. In 1966, Criley et al. introduced the term “prolapse,” recognizing cine-angiographically an MR [Figure 1], which occurs in association with a murmur in the latter part of systole or marked accentuation of a soft holosystolic murmur in late systole.[8] He sustained that the difference between billowing and prolapse might merely be semantic or only a matter of degree, with one condition merging into the other.[8] The introduction of the term “prolapse” has contributed to the general confusion. Then, Alain Carpentier defined the essential differences between prolapse and billowing: he restricted the use of the term “prolapse” to the failure of the leaflet edges to oppose normally.[9] Such partial loss of apposition may occur with or without abnormal billowing of the bellies of the leaflets, and MR, albeit mild, or even minimal, will inevitably result. If the billowing of the mitral leaflet is extreme with very voluminous leaflets and elongated chordae, the term “floppy” is appropriate.[9] Leaflet “flail” implies coaptation failure with eversion of the free edge of a leaflet into the LA, usually consequent to chordal rupture.[9],[10] When symptoms, electrocardiographic changes, arrhythmias, or other features occur, the recognition of a syndrome is justified.[9]
Figure 1: Cine-angiographically mitral regurgitation in MVP. Left heart cineangiocardiography demonstrated aneurysmal bulging of one or both leaflets of the mitral valve into the left atrium in early systole, followed by mitral regurgitation in the latter part of systole. *Mitral regurgitation

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In the early days of 2D echocardiography, the MVP was overdiagnosed, in part for the erroneous assumption that the MV was planar. In the late 1980s, using 3-dimensional echocardiographic imaging, Levine and colleagues established that the mitral annulus was saddle shaped and in four-chamber view, the leaflets can appear to “break” the annular plane (creating the appearance of prolapse) when they are normal.[11] Echocardiographic MVP has since been defined as single-leaflet or bileaflet prolapse of at least 2 mm beyond the long-axis annular plane, with or without mitral leaflet thickening. Prolapse with thickening of the leaflets >5 mm is called classic prolapse whereas prolapse with lesser degrees of leaflet thickening is regarded as nonclassic prolapse.[3],[11]


  Pathophysiology and Histology Top


There is a variety of biological, biochemical, and biomechanical factors involved in the development of MVP. Morphologic alteration of the MV apparatus leads to enhancement of localized stress and tissue degeneration. The underlying mechanisms for the development of MVP and MR in association with MV tissue remodeling are still unclear. Myxomatous transformation is the most important mechanism responsible for MVP and the associated click.[1] It is characterized by disruption and loss of normal valvular architecture with thickening of the spongiosa, which is rich in acid mucopolysaccharides. The thickened spongiosa encroaches on the fibrosa, interrupting it focally and causing a basic weakness of this supporting structure, and leading to redundancy and prolapse.[12] Similarly, myxoid replacement of the collagen of chordae tendineae is frequent, leading to their rupture.[6] Furthermore, the expression of proteoglycans and catabolic enzymes is increased, included matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13) that contribute to the fragmentation of elastin and collagen fibers.[10] Myxomatous MV tissue generally exhibits lower stiffness values with lower failure stresses compared to normal MV tissue. The MV annulus is usually enlarged.[13] The so-called “Barlow disease” is an extreme form of degenerative mitral valve disease, characterized by excess connective tissue, redundant, thickened leaflets, marked annular dilatation, elongated, and thin (or thick/calcified) chordae.[10] On the other side, the fibroelastic deficiency is associated with thin, translucent leaflets, with collagen, elastin, and proteoglycans deficiency, moderate annular dilatation, and focal chordal elongation or rupture.[14]

Many studies in patients with MVP who died suddenly have shown a possible role for annular circumference, leaflet length and thickness, and the presence of endocardial plaques in the SCD.[15],[16] More recently, Basso et al. have shown that fibrosis of the papillary muscles and inferobasal left ventricular (LV) wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark of ventricular arrhythmias origin and contrast-enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification.[17]


  Classification of Mitral Valve Prolapse Top


MVP can be distinguished into primary MVP and secondary or syndromic MVP, in the presence of connective tissue disorders such as Marfan syndrome (MFS), Loeys–Dietz syndrome, Ehlers–Danlos syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, and the recently reported aneurysms-osteoarthritis syndrome.[3],[18],[19],[20],[21],[22] MVP has also been observed in hypertrophic cardiomyopathy.[23]

MFS is a multisystemic genetic condition affecting connective tissue. It has a worldwide prevalence of about 1 in 5000 and affects all races equally.[24] It results from heterozygous mutation in the gene that encodes fibrillin-1, which is the most important component of the extracellular matrix.[10] The connective tissue is “weak,” which accounted for the dilatation of the sinuses of Valsalva, aortic dissection, dislocation of the lens, scoliosis, and pneumothoraces. Patients with MFS often have MV elongation and thickening-like Barlow disease morphology.[25] Reports demonstrate that MV dysfunction is present in 80% of patients with MFS, and by age 30 years, moderate to MV occurs in 1 in 8 of them.[26],[27] If severe, MVP and regurgitation may evolve as progressive LV dilation and dysfunction and eventually, heart failure. Mas-Stachurska et al. showed increased collagen deposition and fibrosis in the LV myocardium of Marfan mice.[28] They demonstrated, in the murine model, the positive impact of moderate dynamic exercise on Marfan cardiomyopathy as evidenced by an antihypertrophic effect and the absence of deleterious effects on LV myocardial fibrosis.[28] Athletes with MFS can participate in low and moderate static/low dynamic competitive sports if they do not have aortic root dilatation, moderate-to-severe MR, and family history of dissection or SCD in a Marfan relative.[29]

Loeys–Dietz syndrome, which has phenotypic overlap with MFS, is characterized by aortic aneurysm, dissection, arterial tortuosity, hypertelorism and often long-bone overgrowth, and MVP.[10] It is associated with mutations of gene encoding the components of family of TGF-beta receptors.[10] Aneurysms-osteoarthritis syndrome is a very similar condition, associated with mutations of gene encoding Smad3 proteins, in which MVP is reported in 50% of patients.[30],[31]


  Clinical and Electrocardiographic Findings Top


MVP is usually asymptomatic and with benign natural history. Chest pain, dyspnea, fatigue, dizziness, palpitation, and neuropsychiatric disorders are encountered in patients with MVP[1] and might originate from neuroendocrine and autonomic dysfunction. This neurophysiological association of the heart in case of MVP, renal, and adrenal function with the autonomic nervous system is described in the literature as a “neuroendocrine cardiovascular process,” which may explain many symptoms including heart rhythm disorders.[32]

Auscultatory findings

There are seven major auscultatory manifestations of MVP as follows: isolated mid-systolic click, mid-systolic click followed by a late-systolic murmur, early systolic click, isolated late-systolic murmur, pansystolic murmur, precordial honk, and “silent” form. Physiologic and pharmacologic maneuvers can alter the timing of the click and murmur.[1] The mid-to-late systolic click is generally accepted as the diagnostic hallmark of this syndrome.[1] The general physical appearance in MVP may be entirely normal. However, certain features, that is, asthenic body habitus, high-arched palate, and thoracic skeletal abnormalities (straight back, pectus excavatum, and scoliosis), are frequently noted and heighten suspicion of this condition.[33]

Electrocardiographic findings

Initially, inverted or totally inverted T waves with or without ST-segment depression, primarily in the inferior limb leads might be present in the electrocardiogram of MVP patients. Biphasic or negative T waves might be present but are not uncommon in the athletes and are not necessarily due to MVP.[1] Ventricular and atrial arrhythmias are probably the most common manifestation of MVP. Ventricular fibrillation is the probable mechanism of SCD, a rare occurrence in MVP;[17] however, its mechanism is not clear.

The classical MVP was followed by more frequent and potentially malignant cardiac rhythm disorders compared to the nonclassical primary prolapse of the mitral valve.[32] Recently, Caselli et al. have analyzed twenty-four-hour ambulatory ECG monitoring of 188 athletes with MVP.[34] They have noted that ventricular arrhythmias, which were detected in 29% of MVP athletes, were likely an epiphenomenon of increased myocardial stress and hemodynamic load, as suggested by the larger LV and LA size, mild increase in pulmonary artery systolic pressure, and more frequent MR.[34]


  Noninvasive Imaging Top


Transthoracic echocardiography

MVP is defined by abnormal systolic bulging or “billowing” of one or both leaflets toward the LA with displacement of coaptation point into the LA (>2 mm beyond a line connecting the annular hinge point, ideally in parasternal long-axis view) [Figure 2]. The diagnosis of MVP should be avoided in the apical four-or two-chamber windows as these windows image the MV annulus along the low points of the saddle-shaped MV annulus, falsely making the leaflets appear to be displaced into the LA from the annular plane.[35],[36] MVP regurgitation is typically in mid-to-late systole, while functional MR is often seen during early-to-mid systole.[37] Other findings might be evaluated by transthoracic echocardiography (TTE):
Figure 2: Transthoracic echocardiography parasternal long-axis view with and without color Doppler. Mitral valve prolapse (A2 and P2 scallops) with severe mitral regurgitation

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  • Leaflet length and thickness: normal length is 22–23 mm for the anterior leaflet and 12–13 mm for the posterior. The thickness should be calculated in the parasternal long-axis view in tele-diastole and normally is 2–3 mm. In patients with MVP, leaflets are generally elongated and thickened. “Classic MVP” is characterized by a leaflet thickening >5 mm[10]
  • Mitral annulus diameter: normal value is between 28 and 30 mm.[10] In patients with MVP, the annulus is usually enlarged.[10] Fukuda et al. demonstrated the basal predominance of LV dilatation and reduced contraction in MVP using 2-dimensional TTE and speckle tracking.[38] They showed that the reduction of basal wall motion was proportional to the annular dilatation but not associated with LV ejection fraction or MR volume, suggesting that annular dilatation is associated with basal LV abnormality and annuloplasty might improve the basal LV wall motion.[38] Annular dilatation is also associated with annular flattening[39] and mitral annular disjunction (MAD) [Figure 3]. The normal annulus contracts and increases in saddle-shaped planarity during systole, but in MVP annular flattening increases stress on the leaflets and chordae, which can accelerate the degenerative processes. Normally, the motion of the annulus is passively determined by contraction and relaxation of adjacent ventricular musculature and by the motion of the aortic root.[40] MAD is an anatomic abnormality of the annulus described pathologically as a wide separation between the atrium–MV junction and the LV attachment that is appreciable on both gross and histologic examination.[40] During the surgery, MAD can be detected as superior displacement or atrialization of the posterior leaflet base, and both TTE and transesophageal echocardiography (TEE) can recognize it[40],[41],[42],[43]
  • MR severity: a determination of MR severity is important since mild regurgitation does not lead to remodeling of cardiac chambers and has a benign clinical course, whereas severe regurgitation is associated with significant remodeling, morbidity, and high mortality.[37] According to recent guidelines, MR evaluation is possible through color Doppler (regurgitant jet area, vena contracta, and flow convergence PISA), continuous wave Doppler, and pulsed wave Doppler.[37],[44] Color Doppler M-mode is useful for determine temporal variations of the extension of the proximal flow convergence region due to variations of the regurgitant orifice area throughout systole in MR depending largely on the mechanism of regurgitation: in MVP, there is a small proximal flow convergence region during early systole that increased during midsystole and reached a typical maximum in late systole.[45],[46] To evaluating the hemodynamics consequences of MR, the pulmonary veins flow, and the assessment of LA and LV volumes are necessary.[37] LA dilation is also an expected consequence of severe MR. A normal LA size generally excludes severe chronic MR.[37] LV and LA deformation parameters could help unmask incipient myocardial dysfunction in patients with MVP especially in those with severe MR and yet normal LVEF.[47],[48],[49],[50]
Figure 3: The scheme shows mitral annular disjunction. Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus and is pathologically defined by a separation between the atrial wall-mitral valve junction and the left ventricular attachment. Mitral annular disjunction can cause hypermobility of the mitral valve apparatus and is often associated with mitral valve prolapse

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Although his limited use for the diagnosis of MVP, on M-mode pansystolic sagging (hammocking) or late-systolic dipping of the mitral valve echo are the characteristic findings. Hammocking is affected by the position of the transducer, being induced by a high position, and masked by a low position.[35],[37]

A flail leaflet is part of the MVP spectrum and occurs most commonly from rupture of the marginal chords: the leaflet edge is located in the LA with free motion. A flail leaflet almost always denotes severe MR and is clearly associated with adverse outcomes.[37],[51]

Recently, Muthukumar et al. have described that the “Pickelhaube sign,” the high-velocity systolic signal with tissue Doppler imaging resembling a spiked helmet, was an indicator of a malignant phenotype in MVP.[52] They hypothesize that the tugging of the posteromedial papillary muscle in midsystole by the myxomatous prolapsing leaflets causes the adjacent posterobasal LV wall to be pulled sharply toward the apex, resulting in the observed spiked configuration of the lateral annular velocities.[52] It is possible that this mechanical traction is arrhythmogenic with early electrical dysfunction being recognized during electrophysiological studies even in the absence of gadolinium enhancement on CMR.[53] [Table 1] shows the MVP “spectrum”.
Table 1: The table shows the mitral valve prolapse spectrum

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Transesophageal echocardiography

TEE is indicated to evaluate MR severity in patients in whom TTE is inconclusive or technically difficult, to identify the localization of MVP and for planning MV surgery or percutaneous valve procedures.[37] More recently, in several studies, it has been demonstrated that three-dimensional (3D)-TEE may be more easy and accurate to identify the locations of MVP [Figure 4]. With 3D-TEE, the entire MV can be visualized in a single image, making it possible to examine both leaflets from the left atrial (surgical) perspective, and allowing more definitive identification of prolapse of individual scallops and segments.[54],[55] Furthermore, TEE has been used as the primary imaging modality for guiding the various steps of percutaneous catheter-based edge-to-edge mitral valve repair with a mitral clip. TEE has been shown to be essential for transseptal puncture guidance, optimal clip positioning, and assessment of the severity of MR before and after final deployment of the clip.[56] In the procedural guidance, 3D TEE has the unique ability to depict the whole scenario in which the procedure takes place in a single 3D, real-time, and easily understandable perspective [Figure 5].[56]
Figure 4: Two-dimensional transesophageal echocardiography: MVP (A2 and P2 scallops). (a-c) midesophageal views, 120°, 0°, 90°, respectively; (d) 0° and 90° midesophageal views with X-plane technique; (e) 90° midesophageal view with and without color flow; (f) transgastric view 90° with and without color flow. These images show A2 and P2 significant prolapse with severe mitral insufficiency

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Figure 5: Transesophageal echocardiography: Three-dimensional presentation of mitral valve – “en-face” view: mitral valve displayed centrally with the aortic valve placed superiorly. Prolapse of P2 segment

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Exercise stress echocardiography

In primary asymptomatic MR, exercise testing allows symptom assessment, confident link of symptoms to valve disease severity, safe deferral of surgery for the next 1 year in patients with preserved exercise capacity, insights into the mechanism of exercise-induced dyspnea, and helps in individual risk stratification.[57] Exercise may unmask the presence of symptoms and establish functional capacity in patients who are sedentary or have equivocal symptoms. Failure of LVEF to increase normally with exercise predicts worse postoperative LV function in primary MR.[58] Increased pulmonary artery pressure during exercise (>60 mmHg) may be important in asymptomatic severe primary MR.[37],[58] Furthermore, the assessment of LV contractile reserve may be useful to improve risk stratification and clinical decision-making in patients with asymptomatic primary MR and seems to be better assessed using exercise-induced changes in LV myocardial longitudinal function rather than in LVEF. In patients with preserved LV function, the absence of LV contractile reserve is independently associated with a two-fold increase in the risk of cardiac events.[59]

Cardiac magnetic resonance

Cardiac magnetic resonance (CMR) is a useful tool for the evaluation of MR severity when an assessment by echocardiography is felt to be unsatisfactory or when there is a discrepancy between MR severity and clinical findings. It has been suggested that CMR is more accurate than echocardiography in assessing organic MR severity, and the CMR-derived quantification portends outcome information.[60],[61],[62] However, the long-term prognostic data associated with the MRI-derived assessment of organic MR are scarce; however, CMR should be considered in those patients when MR severity as assessed by echocardiography is influencing important clinical decisions such as the decision to undergo MR surgery in complex situations.

CMR may provide additional information about the mechanism of MR and myocardial viability, provides quantitative evaluation of chamber size, regurgitant volume, and fraction.[37] The presence of billowing, prolapse or flail segments can be identified by dedicated cine imaging performed through the different scallops of the MV leaflets [Figure 6].[37] In MVP, it is possible to detect myocardial fibrosis, the presence of the so-called “curling,” defined as an unusual systolic motion of the posterior mitral ring on the adjacent myocardium. Marra et al. have shown that MAD and systolic curling of the posterior MV leaflet are associated with LV fibrosis, accounting for the excessive mobility of the MV apparatus, and systolic stretch of the myocardium closely linked to the valve.[63] They found, in their arrhythmic MVP patients, relative hypertrophy and fibrosis of inferobasal wall at CMR, as a substrate of electric instability.[63] They showed an association between MAD, curling, and LV fibrosis. The LV fibrosis was detected by CMR in MVP patients with an arrhythmic malignant profile and confirmed by histology in SCD patients with MVP.[63] Furthermore, papillary muscle fibrosis was identified using late gadolinium enhancement in patients with MVP with a history of ventricular arrhythmias and at least moderate MR.[64]
Figure 6: Mitral valve prolapse at cardiac magnetic resonance and end-systolic four-chamber view. Evidence of bileaflet mitral valve prolapse

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Cardiac multidetector computed tomography

Cardiac multidetector computed tomography has been mainly applied for the diagnosis of valvular heart morphology and function, with simultaneously evaluation of coronary artery. Few studies are available on the diagnostic accuracy for MVP using this tool.[65],[66],[67] Radiation exposure and poor temporal resolution are some of the important limits of cardiac MDTC for the evaluation of MVP.


  Long-Term Outcome and Treatment Top


The outcome of MVP was controversial for a long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of them were also published to late ‘80 of the last century till early ‘00. More studies are needed to identify what patients with MVP are at risk for complications. Although MVP is generally a benign condition,[68],[69] complications, such as MR, atrial fibrillation, CHF, endocarditis, and stroke, are well known. Ventricular arrhythmias and SCD have been reported.[70]

The estimated rate of SCD in MVP ranges from 0.2%/years to 0.4%/years in prospective follow-up studies.[17],[71] LV dysfunction resulting from severe MR identifies a patient subgroup at high risk of SCD.[17] However, life-threatening ventricular arrhythmias also occur in patients with MVP with trivial or absent MR.[17] Basso et al. have shown that the patient with MVP and ventricular arrhythmias at risk of SCD is usually a young adult woman with a mid-systolic click at auscultation, bileaflet involvement of the mitral valve, T-wave abnormalities on inferior leads, and right bundle branch block-type or polymorphic ventricular arrhythmias on electrocardiogram and fibrosis of papillary muscles and inferobasal LV free wall, which correlates well with arrhythmia morphology, pointing to a myocardial stretch by the prolapsing leaflets and elongated chordae.[17]

Several studies have shown that MVP might infrequently become complicated by transient ischemic attacks that are thought to be due to platelet and fibrin embolization originating from the mitral valve especially among young patients.[72],[73] These studies are very dated, and the MVP diagnosis was based on single-dimensional (M-mode) echocardiographic criteria.[73] It is necessary to reconsider the previously describe associations with two- and three-dimensional echocardiographic criteria. Therefore, Gilon et al. have not demonstrated an association between the presence of MVP and acute ischemic neurologic events in young people with new echocardiographic criteria.[74] Orencia et al., in a cohort study, showed that in the absence of ischemic heart disease, CHF, and diabetes mellitus, there was no increase in the risk of stroke in MVP patient compared with the general population.[75]

Infective endocarditis (IE) is a serious condition associated with severe complications including CHF, stroke, systemic emboli, abscess formation, and death in up to 25% of patients.[76] Dated studies have suggested that patients with MVP exhibit an increased risk of IE; however, these risks have never been directly compared with the general population.[71],[77],[78] Moreover, these studies were performed at a time when MVP was overdiagnosed due to imprecise echocardiographic criteria. Recently, Katan et al. have identified all adult Olmsted County residents with MVP diagnosed by echocardiography from January 1989 to December 1998 and cross-matched them with the Rochester Epidemiologic Project-identified Olmsted County cases of IE from January 1986 to December 2006 and have retrospectively analyzed and de novo confirmed each IE case using the modified Duke criteria.[79] They concluded that MVP patients with ≥ moderate mitral MR or a flail leaflet are at notable risk of developing IE compared to those without MR.[79]

A subset of patients with MVP develops CHF secondary to progressive MR.[80] Valvular lesions in MVP can worsen with time, regardless of initial clinical and echocardiographic presentation, although older age and higher initial grade of MR were associated with greater risk for progression.[81]

Treatment

According to the European Society of Cardiology (ESC), urgent surgery is indicated in patients with acute severe MR. In the case of papillary muscle rupture as the underlying disease, valve replacement is in general required. In chronic severe MR surgery is indicated in symptomatic patients with severe primary MR with LV ejection fraction (LVEF) ≥30% and in asymptomatic patients with LV dysfunction (LV diastolic diameter [LVESD] ≥45 mm and/or LVEF ≤60%/≥40 mm for the American College of Cardiology/American Heart Association).[82] Surgery should be considered in asymptomatic patients with preserved LV function (LVESD45 mm and LVEF >60%) and atrial fibrillation secondary to MR or pulmonary hypertension.[83] In patients with flail leaflet, an LVESD of 40–44 mm has been reported to predict a worse outcome compared with LVESD <40 mm, and then in these cases, surgery should be considered in asymptomatic patients with preserved LVEF (>60%) and LVESD 40–44 mm when a durable repair is likely, surgical risk is low, and the repair is performed in a heart valve center.[83] Percutaneous edge-to-edge procedure may be considered in patients with symptomatic severe primary MR who fulfill the echocardiographic criteria of eligibility and are judged inoperable or at high surgical risk by the heart team.[83] When feasible, valve repair is the preferred treatment.[83] When surgery is not possible, medical treatment (vasodilators, diuretics, and angiotensin-converting enzyme inhibitors) should be considered for the management of MR and CHF.[82],[84]


  Exercise Performance in Patients with Mitral Valve Prolapse Top


During exercise, recruitment in LV function allows to adequately adapt LV forward stroke volume and cardiac output to central and peripheral demands. In addition to chronotropic adaptation, LV improves contractility with an increase in longitudinal shortening, circumferential, and radial thickening. Patients with dynamic primary MR may have intermittent increase in MR. Hence, MR severity evaluated at rest does not correspond to MR severity experienced in daily life activities.[59]

Data on the effects of exercise on LV performance in patients with severe MR secondary to MVP are limited and dated. Moreover, previous studies of exercise responses in patients with severe MR and MVP have included heterogeneous patient populations. Tischler et al. have shown in asymptomatic patients with chronic, severe MR and normal LVEF at rest, there is an improvement in LV function and an increase in forward stroke volume during exercise. These effects are comparable to those observed in normal controls.[85] Gottdiener et al. have analyzed 39 patients with MVP and no significant MR or coronary artery disease (CAD). They observed that the exercise EF was below the lower limits of normal in 23% of the patients. They also observed that chest pain, arrhythmias, and the pattern and extent of MVP by echocardiography are not independently associated with impairment of LV reserve.[86] In the study of Newman et al., the EF response to exercise was considered normal in 12 patients with MVP and angiographically normal coronary arteries and in 11 patients with MVP and low pretest probability of CAD.[87] These studies did not explore the relationship between age and gender to the EF response to exercise. Iskandrian et al. have demonstrated that patients with MVP have an abnormal LVEF response to exercise in the absence of clinically important MR and in the absence of associated CAD. Furthermore, the abnormality in LV functional reserve is related to both age and gender.[88] More recent data have shown that organic MR due to MVP does not have the dynamic component that characterizes ischemic MR. The effective regurgitant orifice (ERO) in MVP patients was stable during exercise and is a major determinant of survival in patients with asymptomatic organic MR.[89],[90]


  Eligibility in Competitive Sports Top


In 2005, the American Heart Association (AHA) and the American College of Cardiology (ACC) released the following recommendations regarding athletic participation in patients with MVP:[29]

  • Athletes with MVP can engage in all competitive sports without any of the following features: prior syncope, judged probably to be arrhythmogenic in origin; sustained or repetitive and nonsustained supraventricular tachycardia or frequent and/or complex ventricular tachyarrhythmias on ambulatory Holter monitoring; severe MR assessed with color-flow imaging; LV systolic dysfunction (EF <50%); prior embolic event; and family history of MVP-related sudden death.


Athletes with MVP and any of the aforementioned disease features can participate in low-intensity competitive sports only (Class IA). Examples include bowling, golf, and riflery.[29]

The ESC not only released similar recommendations for participation in competitive sports but also added that those with long QT interval should not engage in competitive sports.[91] All athletes with MVP should have annual follow-up with cardiology to monitor for any of the above high-risk features or progression of MR.

Beta-blockers can be used for symptom relief from premature atrial or ventricular contractions. Palpitations should be evaluated with ambulatory electrocardiographic monitoring, and the detection of ventricular tachycardia should be followed by electrophysiology testing to determine the need for an implantable cardioverter defibrillator.[91]

Athletes with MR should undergo annual evaluations, including physical examination, echocardiogram, and exercise stress testing, that simulate the amount of activity, they will be participating in.[92] In 2015, the AHA and ACC released the following recommendations regarding athletes with MR:[92]

  • Athletes with MR should be evaluated annually to determine whether sports participation can continue (Class I; Level of Evidence C)
  • Exercise testing to at least the level of activity achieved in competition and the training regimen is useful in confirming asymptomatic status in patients with MR (Class I; Level of Evidence C)
  • Athletes with mild-to-moderate MR who are in sinus rhythm with normal LV size and function and with normal pulmonary artery pressures can participate in all competitive sports (Class I; Level of Evidence C)
  • It is reasonable for athletes with moderate MR in sinus rhythm with normal LV systolic function at rest and mild LV enlargement (compatible with that which may result solely from athletic training [LVEDD <60 mm or <35 mm/m2 in men or <40 mm/m2 in women]) to participate in all competitive sports (Class IIa; Level of Evidence C)
  • Athletes with severe MR in sinus rhythm with normal LV systolic function at rest and mild LV enlargement (compatible with that which may result solely from athletic training [LVEDD <60 mm or <35.3 mm/m2 in men or <40 mm/m2 in women]) can participate in low-intensity and some moderate-intensity sports (Classes IA, IIA, and IB) (Class IIb; Level of Evidence C)
  • Athletes with MR and definite LV enlargement (LVEDD ≥65 mm or ≥35.3 mm/m2 [men] or ≥40 mm/m2 [women]), pulmonary hypertension, or any degree of LV systolic dysfunction at rest (LV ejection fraction <60% or LVESD >40 mm) should not participate in any competitive sports, with the possible exception of low-intensity Class IA sports (Class III; Level of Evidence C)
  • Athletes with a history of atrial fibrillation who are receiving long-term anticoagulation should not engage in sports involving any risk of bodily contact (Class III; Level of Evidence C).


These recommendations are all Level of Evidence C and reflect expert opinion. They, therefore, should be used within the context of individual cases for any discussions and shared decision-making on restriction from athletic participation. Further study is needed to elucidate the significance of mitral valve disease in athletes.[92] In evaluating the young athlete with MVP, MFS should be ruled out because the risk of aortic rupture and dissection in this syndrome represents a contraindication to competitive activities and contact sports particularly if dilation of the ascending aorta is present.[92]

In Italy since 1982, every athlete had to undergo a clinical evaluation to obtain eligibility for competitive sports.[93] The goal of preparticipation screening of the athletic population is to identify athletes who have cardiovascular abnormalities and consequently to reduce the risk of sudden death during sports activity.[93] According to these guidelines, athletes with MVP should be prohibited from participating in competitive sports if they show the following conditions:

  • Unexplained syncope, family history of juvenile sudden death, and long QT syndrome
  • Moderate-to-severe MR
  • Recurrent supraventricular tachyarrhythmias or complex ventricular arrhythmias at rest and/or during exercise and/or with right bundle branch block morphology[94]
  • Negative T waves in inferior or lateral electrocardiographic leads.[94]


A 6-month eligibility period for competitive sports activities of Groups A and B (horse riding and sailing) may be considered in athletes with mild MR with redundant or myxomatous leaflets. The above-mentioned exclusion criteria also apply when tricuspid valve prolapse coexists.[93],[94] [Table 2] summarizes the most important eligibility criteria, according to the international societies of cardiology [Table 2].
Table 2: Criteria of competitive sport eligibility according to the most important societies of cardiology

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  Conclusions Top


MVP is usually a benign condition that does not require treatment and specific management. SCD is a rare complication, more common in patients with LV dysfunction resulting from severe MR, although recent studies have shown LV and papillary muscles fibrosis in patients with MVP and without moderate-to-severe MR. The American and European societies of cardiology have created recommendations for athletes with MVP, for screening, follow-up, assessment of cardiovascular risks, and progression of MR. In this setting, multimodality imaging techniques have a central role and should provide a broad spectrum of structural and functional information.

Acknowledgments

The authors stated that they had no interests which might be perceived as posing a conflict or bias.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jeresaty RM. Mitral valve prolapse: Definition and implications in athletes. J Am Coll Cardiol 1986;7:231-6.  Back to cited text no. 1
    
2.
Pelliccia A, Caselli S, Sharma S, Basso C, Bax JJ, Corrado D, et al. European Association of Preventive Cardiology (EAPC) and European Association of Cardiovascular Imaging (EACVI) Joint Position Statement: Recommendations for the indication and interpretation of cardiovascular imaging in the evaluation of the athlete's heart. Eur Heart J 2018;39:1949-69.  Back to cited text no. 2
    
3.
Delling FN, Vasan RS. Epidemiology and pathophysiology of mitral valve prolapse: New insights into disease progression, genetics, and molecular basis. Circulation 2014;129:2158-70.  Back to cited text no. 3
    
4.
Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol 2003;42:1959-63.  Back to cited text no. 4
    
5.
Farb A, Tang AL, Atkinson JB, McCarthy WF, Virmani R. Comparison of cardiac findings in patients with mitral valve prolapse who die suddenly to those who have congestive heart failure from mitral regurgitation and to those with fatal noncardiac conditions. Am J Cardiol 1992;70:234-9.  Back to cited text no. 5
    
6.
Rabkin E, Aikawa M, Stone JR, Fukumoto Y, Libby P, Schoen FJ, et al. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation 2001;104:2525-32.  Back to cited text no. 6
    
7.
Cheng TO. John B. Barlow: The man and his syndrome. Int J Cardiol 2014;177:311-6.  Back to cited text no. 7
    
8.
Criley JM, Lewis KB, Humphries JO, Ross RS. Prolapse of the mitral valve: Clinical and cine-angiocardiographic findings. Br Heart J 1966;28:488-96.  Back to cited text no. 8
    
9.
Barlow JB, Pocock WA. Billowing, floppy, prolapsed or flail mitral valves? Am J Cardiol 1985;55:501-2.  Back to cited text no. 9
    
10.
Levine RA, Hagége AA, Judge DP, Padala M, Dal-Bianco JP, Aikawa E, et al. Mitral valve disease – Morphology and mechanisms. Nat Rev Cardiol 2015;12:689-710.  Back to cited text no. 10
    
11.
Levine RA, Stathogiannis E, Newell JB, Harrigan P, Weyman AE. Reconsideration of echocardiographic standards for mitral valve prolapse: Lack of association between leaflet displacement isolated to the apical four chamber view and independent echocardiographic evidence of abnormality. J Am Coll Cardiol 1988;11:1010-9.  Back to cited text no. 11
    
12.
Guthrie RB, Edwards JE. Pathology of the myxomatous mitral value. Nature, secondary changes and complications. Minn Med 1976;59:637-47.  Back to cited text no. 12
    
13.
Choi A, McPherson DD, Kim H. Biomechanical evaluation of the pathophysiologic developmental mechanisms of mitral valve prolapse: Effect of valvular morphologic alteration. Med Biol Eng Comput 2016;54:799-809.  Back to cited text no. 13
    
14.
Fornes P, Heudes D, Fuzellier JF, Tixier D, Bruneval P, Carpentier A, et al. Correlation between clinical and histologic patterns of degenerative mitral valve insufficiency: A histomorphometric study of 130 excised segments. Cardiovasc Pathol 1999;8:81-92.  Back to cited text no. 14
    
15.
Davies MJ, Moore BP, Braimbridge MV. The floppy mitral valve. Study of incidence, pathology, and complications in surgical, necropsy, and forensic material. Br Heart J 1978;40:468-81.  Back to cited text no. 15
    
16.
Chesler E, King RA, Edwards JE. The myxomatous mitral valve and sudden death. Circulation 1983;67:632-9.  Back to cited text no. 16
    
17.
Basso C, Perazzolo Marra M, Rizzo S, De Lazzari M, Giorgi B, Cipriani A, et al. Arrhythmic mitral valve prolapse and sudden cardiac death. Circulation 2015;132:556-66.  Back to cited text no. 17
    
18.
Abdul Wahab A, Janahi IA, Eltohami A, Zeid A, Faiyaz Ul Haque M, Teebi AS, et al. A new type of ehlers-danlos syndrome associated with tortuous systemic arteries in a large kindred from qatar. Acta Paediatr 2003;92:456-62.  Back to cited text no. 18
    
19.
Hortop J, Tsipouras P, Hanley JA, Maron BJ, Shapiro JR. Cardiovascular involvement in osteogenesis imperfecta. Circulation 1986;73:54-61.  Back to cited text no. 19
    
20.
Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006;355:788-98.  Back to cited text no. 20
    
21.
Roman MJ, Devereux RB, Kramer-Fox R, Spitzer MC. Comparison of cardiovascular and skeletal features of primary mitral valve prolapse and Marfan syndrome. Am J Cardiol 1989;63:317-21.  Back to cited text no. 21
    
22.
Rubegni P, Mondillo S, De Aloe G, Agricola E, Bardelli AM, Fimiani M, et al. Mitral valve prolapse in healthy relatives of patients with familial pseudoxanthoma elasticum. Am J Cardiol 2000;85:1268-71.  Back to cited text no. 22
    
23.
Maron BJ, Epstein SE. Hypertrophic cardiomyopathy. Recent observations regarding the specificity of three hallmarks of the disease: Asymmetric septal hypertrophy, septal disorganization and systolic anterior motion of the anterior mitral leaflet. Am J Cardiol 1980;45:141-54.  Back to cited text no. 23
    
24.
Chan YC, Ting CW, Ho P, Poon JT, Cheung GC, Cheng SW, et al. Ten-year epidemiological review of in-hospital patients with Marfan syndrome. Ann Vasc Surg 2008;22:608-12.  Back to cited text no. 24
    
25.
Thacoor A. Mitral valve prolapse and Marfan syndrome. Congenit Heart Dis 2017;12:430-4.  Back to cited text no. 25
    
26.
Pyeritz RE, Wappel MA. Mitral valve dysfunction in the Marfan syndrome. Clinical and echocardiographic study of prevalence and natural history. Am J Med 1983;74:797-807.  Back to cited text no. 26
    
27.
Pyeritz RE. Etiology and pathogenesis of the Marfan syndrome: Current understanding. Ann Cardiothorac Surg 2017;6:595-8.  Back to cited text no. 27
    
28.
Mas-Stachurska A, Siegert AM, Batlle M, Gorbenko Del Blanco D, Meirelles T, Rubies C, et al. Cardiovascular benefits of moderate exercise training in Marfan syndrome: Insights from an animal model. J Am Heart Assoc 2017;6. pii: e006438.  Back to cited text no. 28
    
29.
Maron BJ, Ackerman MJ, Nishimura RA, Pyeritz RE, Towbin JA, Udelson JE, et al. Task force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 2005;45:1340-5.  Back to cited text no. 29
    
30.
van de Laar IM, van der Linde D, Oei EH, Bos PK, Bessems JH, Bierma-Zeinstra SM, et al. Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome. J Med Genet 2012;49:47-57.  Back to cited text no. 30
    
31.
van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, et al. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nat Genet 2011;43:121-6.  Back to cited text no. 31
    
32.
Hodzic E. Assesment of rhythm disorders in classical and nonclassical mitral valve prolapse. Med Arch 2018;72:9-12.  Back to cited text no. 32
    
33.
Criley JM, Heger J. Prolapsed mitral leaflet syndrome. Cardiovasc Clin 1979;10:213-33.  Back to cited text no. 33
    
34.
Caselli S, Mango F, Clark J, Pandian NG, Corrado D, Autore C, et al. Prevalence and clinical outcome of athletes with mitral valve prolapse. Circulation 2018;137:2080-2.  Back to cited text no. 34
    
35.
Waller BF, Maron BJ, Del Negro AA, Gottdiener JS, Roberts WC. Frequency and significance of M-mode echocardiographic evidence of mitral valve prolapse in clinically isolated pure mitral regurgitation: Analysis of 65 patients having mitral valve replacement. Am J Cardiol 1984;53:139-47.  Back to cited text no. 35
    
36.
Correction. Circulation 2015;131:e535.  Back to cited text no. 36
    
37.
El-Tallawi KC, Messika-Zeitoun D, Zoghbi WA. Assessment of the severity of native mitral valve regurgitation. Prog Cardiovasc Dis 2017;60:322-33.  Back to cited text no. 37
    
38.
Fukuda S, Song JK, Mahara K, Kuwaki H, Jang JY, Takeuchi M, et al. Basal left ventricular dilatation and reduced contraction in patients with mitral valve prolapse can be secondary to annular dilatation: Preoperative and postoperative speckle-tracking echocardiographic study on left ventricle and mitral valve annulus interaction. Circ Cardiovasc Imaging 2016;9. pii: e005113.  Back to cited text no. 38
    
39.
Lee AP, Hsiung MC, Salgo IS, Fang F, Xie JM, Zhang YC, et al. Quantitative analysis of mitral valve morphology in mitral valve prolapse with real-time 3-dimensional echocardiography: Importance of annular saddle shape in the pathogenesis of mitral regurgitation. Circulation 2013;127:832-41.  Back to cited text no. 39
    
40.
Lee AP, Jin CN, Fan Y, Wong RH, Underwood MJ, Wan S, et al. Functional implication of mitral annular disjunction in mitral valve prolapse: A Quantitative dynamic 3D echocardiographic study. JACC Cardiovasc Imaging 2017;10:1424-33.  Back to cited text no. 40
    
41.
Eriksson MJ, Bitkover CY, Omran AS, David TE, Ivanov J, Ali MJ, et al. Mitral annular disjunction in advanced myxomatous mitral valve disease: Echocardiographic detection and surgical correction. J Am Soc Echocardiogr 2005;18:1014-22.  Back to cited text no. 41
    
42.
Newcomb AE, David TE, Lad VS, Bobiarski J, Armstrong S, Maganti M, et al. Mitral valve repair for advanced myxomatous degeneration with posterior displacement of the mitral annulus. J Thorac Cardiovasc Surg 2008;136:1503-9.  Back to cited text no. 42
    
43.
Carmo P, Andrade MJ, Aguiar C, Rodrigues R, Gouveia R, Silva JA, et al. Mitral annular disjunction in myxomatous mitral valve disease: A relevant abnormality recognizable by transthoracic echocardiography. Cardiovasc Ultrasound 2010;8:53.  Back to cited text no. 43
    
44.
Falk V, Baumgartner H, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur J Cardiothorac Surg 2017;52:616-64.  Back to cited text no. 44
    
45.
Grossmann G, Giesler M, Stein M, Kochs M, Höher M, Hombach V, et al. Quantification of mitral and tricuspid regurgitation by the proximal flow convergence method using two-dimensional colour doppler and colour Doppler M-mode: Influence of the mechanism of regurgitation. Int J Cardiol 1998;66:299-307.  Back to cited text no. 45
    
46.
Schwammenthal E, Chen C, Benning F, Block M, Breithardt G, Levine RA, et al. Dynamics of mitral regurgitant flow and orifice area. Physiologic application of the proximal flow convergence method: Clinical data and experimental testing. Circulation 1994;90:307-22.  Back to cited text no. 46
    
47.
Zito C, Carerj S, Todaro MC, Cusmà-Piccione M, Caprino A, Di Bella G, et al. Myocardial deformation and rotational profiles in mitral valve prolapse. Am J Cardiol 2013;112:984-90.  Back to cited text no. 47
    
48.
Cameli M, Lisi M, Righini FM, Focardi M, Alfieri O, Mondillo S, et al. Left atrial speckle tracking analysis in patients with mitral insufficiency and history of paroxysmal atrial fibrillation. Int J Cardiovasc Imaging 2012;28:1663-70.  Back to cited text no. 48
    
49.
Cameli M, Lisi M, Righini FM, Massoni A, Natali BM, Focardi M, et al. Usefulness of atrial deformation analysis to predict left atrial fibrosis and endocardial thickness in patients undergoing mitral valve operations for severe mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol 2013;111:595-601.  Back to cited text no. 49
    
50.
Longobardo L, Todaro MC, Zito C, Piccione MC, Di Bella G, Oreto L, et al. Role of imaging in assessment of atrial fibrosis in patients with atrial fibrillation: State-of-the-art review. Eur Heart J Cardiovasc Imaging 2014;15:1-5.  Back to cited text no. 50
    
51.
Enriquez-Sarano M, Avierinos JF, Ling LH, Grigioni F, Mohty D, Trihouilloy C, et al. Surgical treatment of degenerative mitral regurgitation: Should we approach differently patients with flail leaflets of simple mitral valve prolapse? Adv Cardiol 2004;41:95-107.  Back to cited text no. 51
    
52.
Muthukumar L, Rahman F, Jan MF, Shaikh A, Kalvin L, Dhala A, et al. The pickelhaube sign: Novel echocardiographic risk marker for malignant mitral valve prolapse syndrome. JACC Cardiovasc Imaging 2017;10:1078-80.  Back to cited text no. 52
    
53.
Syed FF, Ackerman MJ, McLeod CJ, Kapa S, Mulpuru SK, Sriram CS, et al. Sites of successful ventricular fibrillation ablation in bileaflet mitral valve prolapse syndrome. Circ Arrhythm Electrophysiol 2016;9. pii: e004005.  Back to cited text no. 53
    
54.
de Groot-de Laat LE, Ren B, McGhie J, Oei FB, Strachinaru M, Kirschbaum SW, et al. The role of experience in echocardiographic identification of location and extent of mitral valve prolapse with 2D and 3D echocardiography. Int J Cardiovasc Imaging 2016;32:1171-7.  Back to cited text no. 54
    
55.
Faletra FF, Demertzis S, Pedrazzini G, Murzilli R, Pasotti E, Muzzarelli S, et al. Three-dimensional transesophageal echocardiography in degenerative mitral regurgitation. J Am Soc Echocardiogr 2015;28:437-48.  Back to cited text no. 55
    
56.
Faletra FF, Pedrazzini G, Pasotti E, Petrova I, Drasutiene A, Dequarti MC, et al. Role of real-time three dimensional transoesophageal echocardiography as guidance imaging modality during catheter based edge-to-edge mitral valve repair. Heart 2013;99:1204-15.  Back to cited text no. 56
    
57.
Dulgheru R, Marchetta S, Sugimoto T, Go YY, Girbea A, Oury C, et al. Exercise testing in mitral regurgitation. Prog Cardiovasc Dis 2017;60:342-50.  Back to cited text no. 57
    
58.
Leung DY, Griffin BP, Stewart WJ, Cosgrove DM 3rd, Thomas JD, Marwick TH, et al. Left ventricular function after valve repair for chronic mitral regurgitation: Predictive value of preoperative assessment of contractile reserve by exercise echocardiography. J Am Coll Cardiol 1996;28:1198-205.  Back to cited text no. 58
    
59.
Magne J, Mahjoub H, Dulgheru R, Pibarot P, Pierard LA, Lancellotti P, et al. Left ventricular contractile reserve in asymptomatic primary mitral regurgitation. Eur Heart J 2014;35:1608-16.  Back to cited text no. 59
    
60.
Penicka M, Vecera J, Mirica DC, Kotrc M, Kockova R, Van Camp G, et al. Prognostic implications of magnetic resonance-derived quantification in asymptomatic patients with organic mitral regurgitation: Comparison with Doppler echocardiography-derived integrative approach. Circulation 2018;137:1349-60.  Back to cited text no. 60
    
61.
Uretsky S, Gillam L, Lang R, Chaudhry FA, Argulian E, Supariwala A, et al. Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: A prospective multicenter trial. J Am Coll Cardiol 2015;65:1078-88.  Back to cited text no. 61
    
62.
Myerson SG, d'Arcy J, Christiansen JP, Dobson LE, Mohiaddin R, Francis JM, et al. Determination of clinical outcome in mitral regurgitation with cardiovascular magnetic resonance quantification. Circulation 2016;133:2287-96.  Back to cited text no. 62
    
63.
Perazzolo Marra M, Basso C, De Lazzari M, Rizzo S, Cipriani A, Giorgi B, et al. Morphofunctional abnormalities of mitral annulus and arrhythmic mitral valve prolapse. Circ Cardiovasc Imaging 2016;9:e005030.  Back to cited text no. 63
    
64.
Han Y, Peters DC, Salton CJ, Bzymek D, Nezafat R, Goddu B, et al. Cardiovascular magnetic resonance characterization of mitral valve prolapse. JACC Cardiovasc Imaging 2008;1:294-303.  Back to cited text no. 64
    
65.
Alkadhi H, Wildermuth S, Bettex DA, Plass A, Baumert B, Leschka S, et al. Mitral regurgitation: Quantification with 16-detector row CT – Initial experience. Radiology 2006;238:454-63.  Back to cited text no. 65
    
66.
Moradi M, Nazari M, Khajouei AS, Esfahani MA. Comparison of the accuracy of cardiac computed tomography angiography and transthoracic echocardiography in the diagnosis of mitral valve prolapse. Adv Biomed Res 2015;4:221.  Back to cited text no. 66
[PUBMED]  [Full text]  
67.
Feuchtner GM, Alkadhi H, Karlo C, Sarwar A, Meier A, Dichtl W, et al. Cardiac CT angiography for the diagnosis of mitral valve prolapse: Comparison with echocardiography1. Radiology 2010;254:374-83.  Back to cited text no. 67
    
68.
Freed LA, Levy D, Levine RA, Larson MG, Evans JC, Fuller DL, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1-7.  Back to cited text no. 68
    
69.
Freed LA, Benjamin EJ, Levy D, Larson MG, Evans JC, Fuller DL, et al. Mitral valve prolapse in the general population: The benign nature of echocardiographic features in the framingham heart study. J Am Coll Cardiol 2002;40:1298-304.  Back to cited text no. 69
    
70.
Avierinos JF, Gersh BJ, Melton LJ 3rd, Bailey KR, Shub C, Nishimura RA, et al. Natural history of asymptomatic mitral valve prolapse in the community. Circulation 2002;106:1355-61.  Back to cited text no. 70
    
71.
Nishimura RA, McGoon MD, Shub C, Miller FA Jr., Ilstrup DM, Tajik AJ, et al. Echocardiographically documented mitral-valve prolapse. Long-term follow-up of 237 patients. N Engl J Med 1985;313:1305-9.  Back to cited text no. 71
    
72.
Barnett HJ, Boughner DR, Taylor DW, Cooper PE, Kostuk WJ, Nichol PM, et al. Further evidence relating mitral-valve prolapse to cerebral ischemic events. N Engl J Med 1980;302:139-44.  Back to cited text no. 72
    
73.
Kouvaras G, Bacoulas G. Association of mitral valve leaflet prolapse with cerebral ischaemic events in the young and early middle-aged patient. Q J Med 1985;56:387-92.  Back to cited text no. 73
    
74.
Gilon D, Buonanno FS, Joffe MM, Leavitt M, Marshall JE, Kistler JP, et al. Lack of evidence of an association between mitral-valve prolapse and stroke in young patients. N Engl J Med 1999;341:8-13.  Back to cited text no. 74
    
75.
Orencia AJ, Petty GW, Khandheria BK, Annegers JF, Ballard DJ, Sicks JD, et al. Risk of stroke with mitral valve prolapse in population-based cohort study. Stroke 1995;26:7-13.  Back to cited text no. 75
    
76.
Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med 2001;345:1318-30.  Back to cited text no. 76
    
77.
Marks AR, Choong CY, Sanfilippo AJ, Ferré M, Weyman AE. Identification of high-risk and low-risk subgroups of patients with mitral-valve prolapse. N Engl J Med 1989;320:1031-6.  Back to cited text no. 77
    
78.
MacMahon SW, Hickey AJ, Wilcken DE, Wittes JT, Feneley MP, Hickie JB, et al. Risk of infective endocarditis in mitral valve prolapse with and without precordial systolic murmurs. Am J Cardiol 1987;59:105-8.  Back to cited text no. 78
    
79.
Katan O, Michelena HI, Avierinos JF, Mahoney DW, DeSimone DC, Baddour LM, et al. Incidence and predictors of infective endocarditis in mitral valve prolapse: A population-based study. Mayo Clin Proc 2016;91:336-42.  Back to cited text no. 79
    
80.
Mills P, Rose J, Hollingsworth J, Amara I, Craige E. Long-term prognosis of mitral-valve prolapse. N Engl J Med 1977;297:13-8.  Back to cited text no. 80
    
81.
Avierinos JF, Detaint D, Messika-Zeitoun D, Mohty D, Enriquez-Sarano M. Risk, determinants, and outcome implications of progression of mitral regurgitation after diagnosis of mitral valve prolapse in a single community. Am J Cardiol 2008;101:662-7.  Back to cited text no. 81
    
82.
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular Heart disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;70:252-89.  Back to cited text no. 82
    
83.
Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2017;38:2739-91.  Back to cited text no. 83
    
84.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 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 Heart J 2016;37:2129-200.  Back to cited text no. 84
    
85.
Tischler MD, Battle RW, Ashikaga T, Niggel J, Rowen M, LeWinter MM, et al. Effects of exercise on left ventricular performance determined by echocardiography in chronic, severe mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol 1996;77:397-402.  Back to cited text no. 85
    
86.
Gottdiener JS, Borer JS, Bacharach SL, Green MV, Epstein SE. Left ventricular function in mitral valve prolapse: Assessment with radionuclide cineangiography. Am J Cardiol 1981;47:7-13.  Back to cited text no. 86
    
87.
Newman GE, Gibbons RJ, Jones RH. Cardiac function during rest and exercise in patients with mitral valve prolapse. Role of radionuclear angiocardiography. Am J Cardiol 1981;47:14-9.  Back to cited text no. 87
    
88.
Iskandrian AS, Heo J, Hakki AH, Mandler JM. Age- and gender-related changes in exercise left ventricular function in mitral valve prolapse. Am J Cardiol 1986;58:117-20.  Back to cited text no. 88
    
89.
Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, Detaint D, Capps M, Nkomo V, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med 2005;352:875-83.  Back to cited text no. 89
    
90.
Pecini R, Dalsgaard M, Møller DV, Jensen MS, Kofoed KF, Nielsen W, et al. Moderate exercise does not increase the severity of mitral regurgitation due to mitral valve prolapse. Echocardiography 2010;27:1031-7.  Back to cited text no. 90
    
91.
Pelliccia A, Fagard R, Bjørnstad HH, Anastassakis A, Arbustini E, Assanelli D, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: A consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005;26:1422-45.  Back to cited text no. 91
    
92.
Bonow RO, Nishimura RA, Thompson PD; Udelson JE, American Heart Association Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and American College of Cardiology. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task force 5: Valvular heart disease: A Scientific Statement from the American Heart Association and American College of Cardiology. Circulation 2015;132:e292-7.  Back to cited text no. 92
    
93.
Biffi A, Delise P, Zeppilli P, Giada F, Pelliccia A, Penco M, et al. Italian cardiological guidelines for sports eligibility in athletes with heart disease: Part 1. J Cardiovasc Med (Hagerstown) 2013;14:477-99.  Back to cited text no. 93
    
94.
Cardiological committee for the sport eligibility. Cardiological protocols for the assessment of competitive sport eligibility 2017. Fifth edition 2017.  Back to cited text no. 94
    


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