How to manage an athlete with mitral valve prolapse

Abstract

Introduction

Under the term degenerative mitral valve prolapse different pathophysiological and clinical entities coexist in a spectrum ranging from Barlow’s disease to fibroelastic deficiency, and represent the most common cause of mitral regurgitation in the general population and in athletes. Carrying a mitral valve prolapse is usually considered a benign condition for athletes, but recently the scientific literature has focused on the malignant, thus rare, arrhythmic mitral valve prolapse and its dramatic association with sudden cardiac death, so that specific features should be considered a red flag and prompt additional exams before clear for competition.

Discussion

As the athlete’s heart is morphologically accompanied by remodelling and dilatation of the cardiac chambers induced by exercise, it may be challenging to differentiate the degree of left ventricular and atrial dilation induced by significant mitral regurgitation from physiological remodelling, especially in endurance athletes.

Conclusion

This how-to article provides clinical and useful data to manage athletes with mitral valve prolapse and to distinguish high-risk athletes carrying the features of arrhythmic mitral valve prolapse.

Degenerative mitral valve prolapse (MVP) is the most common cause of mitral valve (MV) regurgitation in the general population (including athletes) with a prevalence of 2–3%,¹ and tends to be mostly benign. The term ‘mitral valve prolapse’ covers a variety of different pathophysiological and clinical entities, as initially described by Carpentier,² ranging from Barlow’s disease to fibroelastic deficiency, and as such the natural history of MVP can prove highly heterogeneous in nature. Although MVP is usually asymptomatic, complications may occur as the condition progresses towards significant mitral regurgitation (MR), leading to an increased risk of infective endocarditis and heart failure as well as worsening of pulmonary hypertension and right ventricular dilation. However, the most dramatic complication in the athletic population is the risk of ventricular arrhythmias (VAs) leading to sudden cardiac death (SCD). Early identification of athletes affected by MVP is therefore of paramount importance, particularly if high-risk features of potential adverse outcomes are present, which may indeed affect their sports eligibility.

Pathophysiology of MVP

MVP is defined as greater than 2 mm systolic displacement of one or both MV leaflets beyond the annulus into the left atrium. This can result from an isolated elongation or chordal rupture of a single scallop in an otherwise normal valve or in a collagen-deficient valve (fibroelastic deficiency), to a multi-scallop prolapse of one or both leaflets in a valve with diffuse myxomatous excessive tissue and increased annular size, characteristic of Barlow’s disease.³ Molecular changes in the collagen and in the elastic fibres, together with proteoglycan accretion, lead to annular dilation, leaflet redundancy and the presence of excessive tissue. Activated metalloproteinases within the valvular interstitial cells are responsible for extracellular matrix protein disruption, with a consequent increase in mucopolysaccharides.^3–5 Connective tissue diseases such as Marfan syndrome, Ehler–Danlos syndrome and osteogenesis imperfecta may also be associated with excessive MV tissue.

Diagnosis of MVP

History and clinical findings

Athletes affected by MVP are usually asymptomatic at presentation and MVP may be discovered incidentally on auscultation of a mid to late systolic click along with a high-pitch, holosystolic murmur, best heard at the apex. When symptomatic, athletes may mention dyspnoea on exertion, reduced exercise tolerance, palpitations, fatigue and, less commonly, pre-syncope, syncope and cerebrovascular accidents. Physical examination may also reveal Marfanoid habitus (such as tall stature, dolichostenomelia, arm span larger than height, arachnodactyly of hands and feet), as suggested by the revised Ghent criteria that can be applied to rule out Marfan syndrome.⁶ A family history of MVP and SCD must be ruled out in athletes. An echocardiographic screening could be helpful to identify the familial occurrence of a MVP cluster.⁷

Electrocardiography

Electrocardiographic features of patients with MVP could be non-specific, as many subjects may show a normal surface 12-lead electrocardiogram (ECG).

Negative or biphasic T-waves in the inferior leads are associated with MVP-related SCD, and their presence, together with a history of VAs, can be considered a high-risk feature.

Premature ventricular contractions (PVCs) are also relatively common in athletes with MVP and in isolation cannot be considered a high-risk finding. On the contrary, the origin of PVCs is indeed of significance: a right bundle branch block inferior axis morphology, a Purkinje or postero-medial papillary muscle origin (right bundle branch block superior axis), the presence of polymorphic couplets with a variable QRS axis or episodes of non-sustained ventricular tachycardia should prompt the physician for further investigations as an important non-invasive marker of electrical instability⁸ (Figure 1).

Transthoracic echocardiography

This is the safest, most effective, feasible and repeatable imaging technique, allowing optimal visualisation of the entire MV anatomy and function, particularly in athletes who usually have extremely good acoustic windows. Of course, transesophageal echocardiography provides more accurate measurements of the MV apparatus, but its role is currently relegated to preoperative assessment or inconclusive transthoracic echocardiography (TTE), as transthoracic two-dimensional (2D) and three-dimensional (3D) echocardiographic assessment is usually satisfactory. Identification of the aetiology underlying MR is the central objective of a successful diagnostic evaluation. A systematic evaluation should include information on anatomical appearance and haemodynamic performance, supported by quantitative data. Anatomical evaluation of the MV includes assessment not only of the leaflet, the annulus and the chordae, but also of the left ventricle (LV) and left atrium (LA). Mitral annular disjunction (MAD) can also be depicted by echocardiography, even if cardiac magnetic resonance (CMR) is the gold standard imaging technique.

The echocardiographic appearance of leaflet tissue can range from the excessive, myxomatous tissue of Barlow’s disease, to normal tissue in the case of a simple ruptured chordae, or the normal to thin, translucent aspect of the fibroelastic tissue-deficient MV. This latter condition, however, more typically occurs after 60 years of age, but areas of thinned translucent aspect in an otherwise normal valve may be present in younger individuals. Athletes will be mostly affected by Barlow’s disease, characterised by involvement of multiple leaflet segments or both leaflets resulting in a ‘floppy valve’. Simple isolated to diffuse chordal elongation or rupture may be present. Annular dilation also occurs, mainly affecting the posterior part of the MV annulus, which is potentially associated with a certain degree of annular calcification in older ages. Carpentier’s classification² of MV scallops, as P1 antero-lateral, P2 medial and P3 postero-medial, for the posterior leaflet and consequently A1, A2 and A3 for the anterior leaflet, is very helpful in correctly identifying the prolapsing segments and the origin of regurgitant jets, not only in terms of diagnosis, but in order to guide surgical repair if required. While 2D TTE provides a global depiction of all six scallops and of the two commissures by combining the apical and para-sternal window views⁹ (Figure 2), real-time 3D echocardiography offers exceptional volume rendering images that can also be used for quantitative analysis of the prolapsing areas and for better determination of the shape of the MV annulus.¹⁰ Quantification of MR may be challenging and is usually obtained by combining qualitative and quantitative parameters. Athletes usually present with mild or mild to moderate MR, nevertheless specific signs of a moderate to severe or severe MR must be ruled out. These include a flail MV leaflet with a ruptured chorda in the left atrium, a vena contracta width of 0.7 cm or greater, a colour Doppler jet area greater than 40% of the left atrium and a large flow convergence. Supportive signs of the haemodynamic parameters include a dense, triangular continuous wave Doppler MR jet and a MV inflow E-wave of greater than 1.2 m/s.¹¹ Other quantitative parameters, such as effective orifice area, regurgitant volume and regurgitant fraction, are very useful but sometimes limited in the presence of very eccentric jets, as present in flail MR. The evaluation should be completed with assessment of pulmonary artery pressures and eventual reverse flow in the pulmonary veins. Dimensions and volumes of the LV and LA must be carefully evaluated in athletes, because both MR and exercise can synergistically induce chamber dilation. Therefore a certain degree of homogenous dilation of cardiac chambers, particularly in endurance athletes, should be identified as athlete’s heart.^12,13 On the contrary, a definite LV and LA enlargement (left ventricular end-diastolic diameter (LVEDD) >60 mm or >35.3 mm/m² in men and >40 mm/m² in women)¹⁴ associated with severe MR or moderate to severe MR, even in mild pulmonary hypertension and any degree of left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) <60%) must set off an alarm.

Exercise stress echocardiography

Exercise stress echocardiography, reproducing at a minimum the level of activity achieved in competition, is particularly useful in athletes, who have extremely good acoustic windows, to ascertain whether they are asymptomatic, if exercise capacity is preserved and for individual risk stratification. With regard to the latter, evaluation of left ventricular contractile reserve, in particular exercise-induced changes in left ventricular myocardial longitudinal function may be more informative than LVEF alone. Another important parameter is the systolic pulmonary pressure increase during physical effort, as an increase of more than 60 mmHg predicts adverse long-term outcomes, together with: (a) impaired exercise capacity (<85% of age and sex-predicted metabolic equivalents (METs)); (b) impaired heart rate recovery; (c) exercise-induced atrial fibrillation (AF) or complex VAs; and (d) impaired left ventricular contractile reserve.¹¹ On the contrary, dobutamine stress echocardiography has no role in the evaluation of MR dynamics because of its non-physiological effects.¹¹

Cardiac magnetic resonance

CMR could be appropriate if the exact mechanism of MR is unclear or echocardiographic quantification of MR proves difficult, when an accurate diagnosis is important in guiding clinical decision-making and in sports eligibility if debate or high-risk features for arrhythmic MVP are present. In fact, dedicated cine imaging sequences can provide additional information on the presence of billowing, prolapse or flail MV leaflet or MAD, which is the detachment of the MV annulus from the ventricular myocardium (>1 mm) at the base of the posterior leaflet.^15,16 MAD has been identified as a high-risk feature of arrhythmic MVP, as it may induce a further annulus dilation, progression of the leaflet myxomatous degeneration and myocardial stretch in the left ventricular inferior wall at the basal segment.¹⁷ Echocardiography can identify MAD, but CMR is the gold standard imaging technique. At the same time, CMR can provide exact quantification of the MR regurgitant volume and fraction, as well as of cardiac chamber volumes and function, in particular of the LV. Using late gadolinium enhancement (LGE) or T1 mapping, CMR can also detect not only the presence of fibrosis in the left ventricular myocardium, mostly in the infero-basal segment and papillary muscles, which is associated with MAD and arrhythmic malignant MVP, but also a subclinical condition of diffuse interstitial fibrosis that has been proposed as a precursor of focal fibrosis or as a marker of the upregulation of a fibrotic phenotype.¹⁸ The Padua hypothesis¹⁷ postulates that the morphofunctional abnormalities of the mitral annulus (MAD and systolic curling motion) are the basis for the paradoxical increase in the MV annulus during systole, the progressive myxomatous degeneration of the leaflets and the myocardial stretch in the left ventricular inferobasal segment and papillary muscles that cause increased stress leading to hypertrophy and replacement-type fibrosis.

Arrhythmic MVP

MVP in athletes usually carries a benign prognosis, but it can be associated with AF secondary to MR and as strenuous exercise alone can be a trigger for AF, its presence should be carefully evaluated.¹⁹

Moreover, the presence of complex VAs can lead to adverse cardiovascular events and must be carefully ruled out in the presence of high-risk features. Decades ago, MVP-related SCD was considered an extremely rare event, but more recent reports indicate an estimated annual risk of MVP-related SCD due to sustained VAs of 0.2–1.9%.²⁰ Therefore, correct identification of athletes at higher risk of SCD is of pivotal importance; however, although several risk factors have been described, risk stratification has proved particularly challenging (Figure 3). The malignant phenotype has only been described in Barlow’s disease in the presence of a bi-leaflet prolapse, more frequently seen in women.²¹ A positive family history of SCD must be ruled out as well as a history of syncope or pre-syncope. To identify the burden of VAs, a stress ECG test and 24-hour ambulatory ECG monitoring, or in selected cases a 7-day event recorder, are indicated, as the presence of polymorphic VAs associated with moderate or severe MR indicates a higher risk of cardiovascular events, and may suggest the need for surgery.²² The ‘Pickelhaube sign’²³ is a readily obtained echocardiographic parameter that has been proposed to identify those individuals who may show LGE on CMR, and is characterised by a tissue Doppler S-wave peak velocity at the lateral MV of 16 cm/s or greater. Moreover, another feature associated with the presence of VAs and fibrosis is MAD, which is thought to be responsible for the continuous mechanical traction exerted by the prolapsing posterior leaflet, leading to fibrosis of the infero-lateral base of the LV.¹⁵

Certainly, the presence of myocardial scar tissue and complex ventricular ectopy, substrate and trigger, respectively, are two common findings in MVP-related SCD. When associated with a hyperadrenergic state, as occurs during athletic competition, these pathological features act as a transient modulator that may precipitate sustained VAs.

Sports eligibility in athletes with MVP

Usually MVP is a benign condition with an excellent prognosis, and no sports restriction should apply in the absence of significant MR and VAs. Nevertheless the increased haemodynamic load associated with the potential effects of a hyperadrenergic state during competitive sports must be taken into account when evaluating an athlete with MVP,¹⁴ and special attention must be paid to the high-risk features of arrhythmic MVP, regardless of the degree of MR. In fact, in a large cohort of athletes with MVP a small proportion of 0.5% per year rate of adverse cardiovascular events was reported, only in athletes with MVP and VAs, with or without significant MR.²² The presence of both VAs and significant MR yielded the worst outcome and the presence of MAD and higher systolic blood pressure could be considered additional prognostic markers.²²

The 2015 American Heart Association (AHA)/American College of Cardiology (ACC) recommendation²⁴ suggests that athletes with MR should be evaluated yearly to confirm eligibility to engage in competitive sports.

Athletes with MVP in sinus rhythm with mild or moderate MR, normal left ventricular function (LVEF >60%) and dimensions (end-diastolic diameter <60 mm or <35.3 mm/m² in men and <40 mm/m² in women), and systolic pulmonary artery pressure less than 30 mmHg, can engage in all types of sports. When evaluating left ventricular dimensions not only body surface area but also the type of sports should be considered, as endurance sports can further increase left ventricular dimensions, regardless of MR.¹¹

Athletes with severe MR, in sinus rhythm, with normal LVEF (>60%) and normal or mild left ventricular enlargement can participate in low-intensity sports,²⁴ while athletes with moderate or severe MR and confirmed left ventricular enlargement (end-systolic diameter >40 mm) or LVEF impairment (<60%) or pulmonary hypertension (>30 mmHg) should not compete in any type of sports, with the exception of some low-intensity sports, after discussing the risks and potential outcomes with the athlete. When indicated, surgical treatment should be proposed to the athlete. The 2005 consensus document of the working group on sports cardiology of the European Society of Cardiology (ESC)²⁵ recommended that athletes with mild to moderate MR, in sinus rhythm and with normal left ventricular size and function and normal exercise testing could compete in all sports. They proposed the cut-off value of index left ventricular end-systolic volume (<55 ml/m²) to identify those athletes with left ventricular enlargement of clinical relevance, or an ejection fraction less than 50% for left ventricular dysfunction. Athletes with mild to moderate MR and a mild left ventricular dilation (end-systolic volume <55 ml/m²) and normal left ventricular function can compete in low to moderate dynamic and low to moderate static sports, while athletes with significant left ventricular enlargement (end-systolic volume >55 ml/m²) or LVEF less than 50% should be excluded from competitive sports.

We propose a structured algorithm for the assessment of athletes with MVP (Figure 4), which takes into account the presence of more than mild MR and of high-risk features of an arrhythmic MVP, to help the sports cardiologist in the optimal diagnostic evaluation. Particular attention is dedicated to the echocardiographic assessment of an athlete with MVP because it is essential to quantify the grade of MR and to describe its mechanism. The basal and post-exercise or stress ECG are also pivotal to correlate the electrocardiographic with the echocardiographic findings, to identify correctly those athletes with a potential risk who should undergo CMR.

Treatment

If present, hypertension should be appropriately treated to prevent an additional haemodynamic load that can increase left ventricular stress and MR regurgitant volume.²²

Beta-blockers are the preferred first-line drugs to treat VAs, but in athletes sinus bradycardia and doping issues can hamper their use.

At present, insufficient data exist regarding the prophylactic use of defibrillator implantation in primary prevention in individuals with high-risk arrhythmic MVP; however, it may be considered as a valid option in selected cases. Prospective studies are needed to assess the cost-effectiveness of defibrillator implantation in primary prevention in high-risk arrhythmic MVP. The combined use of CMR and electrophysiology studies may be useful in identifying those individuals with polymorphic VAs and left ventricular scar who may benefit the most from defibrillator implantation. Catheter ablation in order to reduce VAs may also be a valid option in selected symptomatic individuals, but consensus is lacking regarding its utility and each case must be discussed individually by a multidisciplinary team.¹⁸

Surgical treatment

Based on the latest ESC/European Association for Cardio-Thoracic Surgery (EACTS) guidelines,²⁶ asymptomatic individuals with severe MR and confirmed left ventricular enlargement evaluated as left ventricular end-systolic diameter (LVESD) of 45 mm or greater, left ventricular systolic function impairment as LVEF of 60% or less have an indication for surgery (class I). Even in the presence of LVESD less than 45 mm and LVEF greater than 60%, in the presence of AF secondary to MR or pulmonary hypertension with systolic pulmonary artery pressure (sPAP) of 50 mmHg or greater should be referred for surgical MV repair (class IIa). Controversy exists in asymptomatic patients with severe MR and LVESD 40–45 mm and LVEF greater than 60% with regard to the optimal timing of surgery. Early surgery or watchful waiting are possible options for asymptomatic patients,²⁷ but early surgery is favoured when a durable repair is likely, surgical risk is low, the repair is performed in a high-volume heart valve centre and there is a flail leaflet or a significant left atrial dilation (left atrial volume index (LAVI) ≥60 ml/m²) in sinus rhythm (class IIa). So, based on these indications, is watchful waiting a real option for an athlete who has been restricted from sports participation? Athletes should be referred to a high-volume reference centre specialising in MV surgery, where MV repair rate success for degenerative MR is greater than 95% even in cases of anterior leaflet or bileaflet prolapse. It is reasonable to consider a less invasive surgical approach by right-sided mini-thoracotomy with or without video assistance or endoscopic robotic valve repair, to ensure better cosmetic results, less blood transfusion requirement and faster return to play,²⁸ even if no prospective data are available in athletes. The optimal repair technique for degenerative MR must aim to restore a good leaflet coaptation line of at least 5 mm, and correct the annular dilation, to ensure durable repair. To obtain these results, the most appropriate leaflet or chordal technique or a combination of both should be selected based on aetiology, exact anatomical lesion and degree of leaflet dysfunction. One surgical leaflet technique, described by Carpentier,² and known as ‘the French correction’, involves quadrangular or triangular leaflet resection of the excess tissue, as seen in Barlow’s disease, generally at the P2 level. Another technique is based on the implant of polytetrafluoroethylene neochordae, to restore support for the prolapsing scallop(s). While both techniques can be applied in the context of a complex repair,^29,30 at present the neochordae implant technique is gaining momentum, favouring the ‘respect rather than resect’ approach in comparison with quadrangular resection. Regardless of the leaflet or chordal technique chosen, a posterior annuloplasty, using a prosthetic ring or a pericardial band, is always necessary to reshape the MV annulus, to restore its circumference and to stabilise the repair.³¹ The combined technique of neochordae implant and posterior annuloplasty has been employed for over 25 years in reference centres with excellent results,³² regardless of prolapse localisation so that MV repair is feasible in almost all cases. Prospective data are needed from high-volume centres with excellent durability of repair to evaluate whether MV repair might be effective in reducing VAs in high-risk arrhythmic MVP.

The possible return to play of selected athletes who underwent MV repair was evaluated in a case-by-case discussion by a multidisciplinary team of experts that can rule out the presence of VAs at stress ECG and 24-hour ambulatory ECG monitoring, residual MR or left ventricular dysfunction at echocardiography at rest and during effort and can strictly follow up the athletes.

Conclusion

When evaluating an athlete with MVP, attention should be paid to certain aspects of this multifaceted pathology in a systematic diagnostic approach, in particular accurate quantification of the MR and identification of high-risk features that can lead to adverse events.

Author contribution

EC and LS contributed to the conception or design of the work. EC, LS and MP drafted the manuscript. GF and FV critically revised the manuscript for intellectual content. All authors gave final approval and agree to be accountable for all aspects of the work ensuring integrity and accuracy.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship and/or publication of this article.

References