Mitral valve prolapse: Overview of complications and their management

INTRODUCTION — Mitral valve prolapse (MVP) is the most common cause of primary mitral regurgitation (MR; eg, 72 percent of cases of moderate to severe primary MR [1]) in resource-abundant countries [2].

MVP is commonly suspected based on auscultatory findings and then confirmed by echocardiography or identified on echocardiography performed for other reasons. Earlier uncertainties regarding MVP complications were clarified after criteria for diagnosis of MVP were corrected to account for the saddle shape of the mitral annulus [3], as discussed separately. (See "Mitral valve prolapse: Clinical manifestations and diagnosis".)

This topic provides an overview of complications of MVP and their management. MVP is a progressive valve lesion that has a genetic basis [4,5] but tends to be fully developed later in life. This progression of the MVP lesions and consequences, physiologic and clinical, are the main source of complications [6,7]. Complications in patients with MVP are dominated by MR and its hemodynamic consequences but also include infective endocarditis, atrial and ventricular arrhythmias, ischemic neurologic events, development of tricuspid regurgitation, heart failure, and, rarely, sudden cardiac death (SCD) [8]. Clinical manifestations, diagnosis, and natural history of MVP are discussed separately. (See "Mitral valve prolapse: Clinical manifestations and diagnosis" and "Pathophysiology and natural history of chronic mitral regurgitation" and "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet".)

TIME COURSE — The mode and presentation of MVP complications can be highly variable:

●Acute presentation is usually the result of the development of heart failure, atrial arrhythmias with rapid ventricular response, ventricular arrhythmias with or without sudden cardiac arrest, bacterial endocarditis, stroke, or acute ruptured chordae with chest pain and shortness of breath.

●Subacute presentation is the most frequent, with the predominant symptom of shortness of breath and, less often, palpitations or syncope.

●Insidious complications occur in patients who remain asymptomatic but who develop complications that are identified during routine follow-up. These include progression of MVP severity (with or without ruptured chord), progression of MR, left ventricular (LV) remodeling/dysfunction, left atrial remodeling, and hemodynamic alterations. While these insidious complications are most prominent with severe MR, occurrence in patients with less than severe MR is possible.

Careful monitoring is recommended to minimize the incidence of clinical complications and mortality, as discussed separately. (See "Chronic primary mitral regurgitation: General management", section on 'Monitoring'.)

MITRAL REGURGITATION — Outcomes in patients with MVP are largely determined by the presence and severity of associated primary mitral regurgitation (MR) and its hemodynamic consequences, including development of heart failure [9,10] (table 1). While MVP represents the most common cause of severe primary MR in resource-abundant countries [1,11], only a minority of patients with MVP ultimately develop symptomatic severe MR due to profound leaflet prolapse and/or chordal rupture. The majority of patients with MVP with no or trivial MR generally incur a low risk of complications in the following years, but MR warrants monitoring.

Routine follow-up is essential for all patients with MVP and MR, with more frequent monitoring for patients with greater MR (larger regurgitant orifice and regurgitant volume), as discussed separately. (See "Chronic primary mitral regurgitation: General management", section on 'Monitoring'.)

Management of primary MR (including MVP with MR) is discussed separately. (See "Chronic primary mitral regurgitation: General management" and "Chronic primary mitral regurgitation: Indications for intervention" and "Chronic primary mitral regurgitation: Choice of intervention".)

HEART FAILURE — In patients with MVP, symptoms and signs consistent with heart failure warrant comprehensive evaluation for cardiac and noncardiac (eg, respiratory) causes using clinical and imaging assessment.

Causes of symptoms of heart failure — Among patients with severe mitral regurgitation (MR), 50 to 60 percent will develop heart failure within 10 years if not treated with mitral valve intervention [12-14].

While the risk of heart failure in patients with MVP is mainly determined by the severity of MR complicating MVP [8,12], other factors may precipitate or exacerbate heart failure, including the presence of other complications of MR (atrial fibrillation [AF], LV dysfunction, pulmonary hypertension, functional tricuspid regurgitation, right ventricular dysfunction) [15-18] and the presence of concurrent conditions (eg, obstructive coronary disease, senile amyloidosis, hypertensive heart disease) [19].

Also, symptoms associated with heart failure, such as shortness of breath, are not specific and may be caused by noncardiac conditions such as pulmonary disease and anemia. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

Importance of mitral valve intervention — If the cause of heart failure in a patients with MVP is determined to be severe MR or complications of MR (eg, AF), medical treatment (eg, diuretic therapy) is only temporizing in preparation for an intervention to correct the MR [9,10]. Even patients who display marked symptomatic improvement or become asymptomatic after an episode of heart failure incur a substantial risk of mortality with continued medical management without mitral valve intervention [13], so mitral intervention should not be delayed in these patients. Undertreatment of MR remains a considerable problem resulting in profound excess mortality [1,20], in part because symptom improvement with medical treatment may be misinterpreted as a sufficient response to avoid mitral intervention. (See "Chronic primary mitral regurgitation: General management", section on 'Treatment of heart failure' and "Chronic primary mitral regurgitation: Indications for intervention".)

In patients who present with AF as the main precipitant of heart failure in the context of moderate or severe MR, the appropriate first course of action is not AF ablation but mitral valve intervention, which is associated with improved outcomes [21]. Indications for mitral valve intervention and choice of mitral valve intervention in patients with MR are discussed separately. (See "Chronic primary mitral regurgitation: Indications for intervention".)

ISCHEMIC NEUROLOGIC EVENTS

Risk of ischemic neurologic events — In patients with MVP, the risk of ischemic neurologic events appears to be associated with thickened myxomatous leaflets and performance of cardiac surgery [22] (particularly mitral surgery, even mitral valve repair [23]) and more strongly associated with the following known risk factors for embolism (irrespective of presence of MVP): occurrence of AF and older age.

Thus, the concept of MR preventing thromboembolic events is not supported by the evidence and, indeed, patients with severe MR who are at high risk for AF and mitral surgery are at increased risk for ischemic neurologic events [22].

The relationship between MVP and risk of ischemic neurologic events (stroke and transient ischemic attack) has long been debated [4]. While some studies identified an association between MVP and risk of ischemic neurologic events, other studies have not. The concept that MVP may be a cause for ischemic neurologic events in young patients stemmed from rare observations of thrombi on the surface of mitral leaflets in patients with MVP [24] and a case control study of young patients with strokes that suggested an excess prevalence of MVP with strokes in this context [25]. However, uncertainty remained because the diagnosis of MVP in the original case-control study [25] was based on outdated invalid criteria [26].

A subsequent case-control study was performed based on the correct diagnostic criteria for MVP, comparing 213 patients ≤45 years old with ischemic stroke or transient ischemic attacks with 263 control subjects. The prevalence of MVP was similar in the two groups (1.9 and 2.7 percent; odds ratio adjusted for age and sex 0.59, 95% CI 0.12-2.50) [27]. However, this study did not exclude a potential link between MVP and ischemic neurologic events over patients' lifetimes.

The risk of ischemic neurologic events (stroke or transient ischemic attack) was examined in a study of 777 patients with MVP (mean age 49 years) who were followed for a mean of 5.5 years [22]. Ischemic neurologic events occurred in 30 patients (4 percent). This event rate was significantly increased compared with the expected rate of neurologic events in the community adjusted for age, sex, and rhythm (relative risk [RR] 2.2, 95% CI 1.5-3.2). The estimated 10-year risk of an ischemic neurologic event under medical management was significantly increased for patients ≥50 years of age (13 percent), for those who developed AF (49 percent), and for those with thickened mitral valve leaflets (6 percent). Independent determinants of ischemic neurologic events were older age (RR 1.08 per year, 95% CI 1.04-1.11), mitral thickening (RR 3.2, 95% CI 1.4-7.4), AF during follow-up (RR 4.3, 95% CI 1.9-10.0), and need for cardiac surgery (RR 2.5, 95% CI 1.1-5.8). Older age and mitral valve thickening remained independent determinants of ischemic neurologic events when analysis was restricted to medical management. The risk of ischemic neurologic events was not increased in patients with MVP without leaflet thickening treated only with medical management but was increased in patients who had undergone mitral surgery.

Antithrombotic therapy — For patients with MVP without history of thromboembolic events, AF, or mitral surgery, routine antithrombotic therapy is not required.

Standard recommendations for antithrombotic therapy apply to patients with MVP who have a concurrent indication for antithrombotic therapy such as transient ischemic attack, ischemic stroke, systemic embolism, or AF. General recommendations for antithrombotic therapy for AF and stroke are presented separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack".)

Recommendations for antithrombotic therapy after mitral valve repair or mitral valve replacement are discussed separately. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair" and "Antithrombotic therapy for mechanical heart valves".)

ATRIAL COMPLICATIONS OF MVP

Atrial dilation — The extent of atrial dilation in patients with MVP and mitral regurgitation (MR) is associated with severity of MR (due to the effects of the regurgitant volume), age, and diastolic dysfunction [28]. However, there is marked individual variation in the degree of left atrial (LA) dilation. Atrial dilation plays an important physiologic role in compensating for the MR associated with MVP and yields reduced (and, in some cases, normalization of) LA pressure even with severe MR [29], frequently with a prolonged asymptomatic phase.

Patients with marked LA dilation are at higher risk of developing subsequent AF [30] and are also at risk of excess mortality [28,31]. Patients with LA dilation identified by LA volume index (LAVI) ≥40 mL/m² are at moderate risk for AF and excess mortality. Those with LAVI ≥60 mL/m² are at high risk for these complications [28,31].

Risk of atrial fibrillation — The risk of AF in patients with MVP is related to severity of MR, age, and atrial size [32,33]. In a study of 246 patients with MVP with MR undergoing mitral valve surgery, the frequency of chronic AF was 15 percent, and paroxysmal AF occurred in another 13 percent [32]. In another study of 89 patients with moderate to severe MR and MVP (without flail leaflet) and 360 patients with flail mitral leaflets, rates of AF were similar in the two groups (41 versus 44 percent at nine years of follow-up) [33]. The incidence of AF in patients diagnosed with severe MR in sinus rhythm has been estimated between 2.2 [13], 5.0 [33], and 5.4 percent [14] per year after the diagnosis of MVP. However, AF rates were much lower in patients younger than 65 than in patients older than 65 (26 versus 65 percent at 10 years) [34].

Among patients with MVP and MR, the occurrence of AF is associated with excess risk of heart failure and mortality [33]. This risk was illustrated by a study of 2425 patients with MVP, flail leaflet, and MR (severe in 94 percent) [21]. Presence of paroxysmal or persistent AF was associated with excess mortality (10-year survival in sinus rhythm, paroxysmal AF, and persistent AF was 74, 59, and 46 percent, respectively) [21]. This difference in survival rates persisted for 20 years independently of other baseline characteristics. Early mitral valve surgery (88 percent mitral valve repair) was associated with a marked survival benefit compared with medical management (adjusted hazard ratio 0.26, 95% CI 0.23-0.30) although survival for patients with AF was still lower than for patients with sinus rhythm (10-year postsurgical survival in sinus rhythm, paroxysmal AF, and persistent AF was 82, 70, and 57 percent, respectively).

Management of atrial fibrillation — In patients with MVP and severe MR, the above-described association between AF and mortality, with improved survival associated with mitral valve surgery [21], supports including the presence of AF (even paroxysmal) as a factor favoring prompt mitral surgery, as discussed separately. (See "Chronic primary mitral regurgitation: Indications for intervention".)

General recommendations for management of AF including treatment for rhythm and/or ventricular rate and indications for anticoagulation also apply to patients with MVP and AF, as discussed separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Management of atrial fibrillation: Rhythm control versus rate control" and "Atrial fibrillation in adults: Selection of candidates for anticoagulation".)

VENTRICULAR ARRHYTHMIAS AND SUDDEN CARDIAC DEATH

Clinical context — The evidence linking MVP to the occurrence of SCD is sparse and relatively weak. The concept that MVP may lead to otherwise unexplained SCD has been based on case reports [35-37] or small case series [38,39] that are not adequate to establish causality. Limited evidence suggests that SCD in patients with MVP is usually due to ventricular fibrillation [36,40].

Consensus documents [41,42] have described two contexts in which the occurrence of SCD among patients with MVP may be observed:

●SCD in MVP patients with severe mitral regurgitation – In such patients, the occurrence of SCD is thought to be related to volume overload. The argument in favor of this hypothesis is that among patients with MVP with severe mitral regurgitation (MR), SCD occurs at a rate higher under medical management than in an age-matched general population, and the rate of SCD after surgical correction of MR is lower, closer to that of the general population [40]. Furthermore, in patients with MVP and asymptomatic severe MR, the fact that the overall mortality rate after surgical correction is similar to that of general population strongly suggests that correction of MR yields normalization of the SCD rate [43]. Overall, the rate of SCD under medical management of severe MR is 1.8 percent per year but is markedly higher in patients with symptoms of heart failure or LV dysfunction [40]. In patients without risk factors, the rate of SCD is 0.8 percent per year under medical management, approximately double the rate of that in the general population [40].

●SCD in MVP independent of MR – Some data suggest that a small subset of patients with MVP have an arrhythmic MVP syndrome, with arrhythmic risk independent of MR severity [41,44]. This proposed syndrome is characterized by severe myxomatous disease with mitral annular disjunction (MAD), nonsustained ventricular tachycardia (NSVT), and risk of SCD. MAD is characterized by systolic separation of the mitral annulus supporting the posterior leaflet from the ventricular myocardium. However, the clinical significance of MAD has been debated, as discussed separately. (See "Mitral valve prolapse: Clinical manifestations and diagnosis", section on 'Mitral annular disjunction'.)

A case series describing 10 cases of "malignant" MVP with bileaflet MVP and cardiac arrest without other explanation for SCD reignited the interest in defining this syndrome [38]. An international cohort of SCD with MVP as the sole possible explanation identified a relatively uniform (nonrandom) MVP phenotype with MAD [45]. In a cohort of 595 patients with MVP, severe NSVT was identified in 9 percent of patients by Holter monitoring [44]. While the subsequent rates of SCD could not be defined, the independent association of severe ventricular arrhythmias with excess subsequent mortality strongly supported a link between MVP and SCD. Furthermore, the cohort verified that severe arrhythmias were associated with a phenotype of MVP including MAD and severe myxomatous disease. Cardiovascular magnetic resonance (CMR) confirmed a link between MAD and ventricular arrhythmias. [46].

The incidence of SCD in patients with MVP without significant MR remains uncertain, and a causal relationship has not been established. Autopsy studies that attempted to define the prevalence of MVP among patients that had suffered SCD and had pathologic verification of the absence of other causes found highly variable prevalence rates of MVP that, overall, were not different from that of MVP in the general population [47-49]. In population-based [41] and referral center [50] cohorts of patients with MVP with various degrees of MR, life expectancy was generally normal for patients with no or mild MR, ruling out a large contingent affected by SCD.

Pathophysiologic mechanisms — Several pathophysiologic mechanisms for arrhythmogenesis have been proposed; the arrhythmic substrate is likely replacement fibrosis that is presumed to result from chronic traction on the papillary muscles and perimitral myocardium by the extensive movement of the prolapsing leaflets and/or the abnormal mitral annulus [51]. Furthermore, increased stretch of myocyte is known to increase the likelihood of ventricular ectopy by prompting afterdepolarization-induced triggered activity, providing the necessary trigger for arrhythmia [51-54]. An additional potential trigger is the mechanical contact of the prolapsing leaflets slamming on the myocardium [55]. Lastly, the Purkinje tissue has been demonstrated to be a main source of ectopy capable of triggering malignant arrhythmia in patients with MVP [56].

On the other hand, both SCD and ventricular tachycardia (VT) can occur in patients without apparent structural heart disease, and excluding such cases may be complex. Specifically, it is difficult to rule out the presence of concurrent mild/early presentation of genetic diseases such as lamin A/C [57], filamin C [58], or long QT syndrome [59] in patients with MVP. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Ventricular tachycardia in the absence of apparent structural heart disease".)

Clinical rhythm monitoring — The role of implantable loop recording (ILR) in patients with MVP is poorly defined, but it is advised in patients with syncope without VT on standard 24 hours ambulatory (Holter) monitoring or for patients with MVP, palpitations, and nondiagnostic Holter monitoring [41].

Studies report high prevalences of atrial arrhythmias (eg, 48 percent) and ventricular arrhythmias (eg, 30 to 43 percent) in patients with MVP [44,60-62]. Severe ventricular arrhythmias (NSVT with rate ≥180 beats per minute [bpm]) has been reported in approximately 9 percent [44]. Most studies have been performed in adults; in children with MVP, ventricular arrhythmias are rare at diagnosis but tend to develop more frequently during follow-up [63].

Risk stratification for SCD and ventricular arrhythmias — The following approach for assessing risk of arrhythmia and SCD is suggested for individuals with MVP, although data to support this approach are limited [41]. It involves two steps; first, analyzing the MVP phenotype to assess the risk of arrhythmia and thereby the intensity of rhythm monitoring and, second, diagnosing the ventricular arrhythmias, symptomatic or not, that may create a high risk of SCD for patients.

Clinical features associated with ventricular arrhythmias or SCD

●Unexplained syncope is a symptom often preceding SCD in patients with MVP [45].

●Severe MR – Patients with at least moderate to severe MR, irrespective of the MVP characteristics, are at heightened risk of SCD, particularly if symptomatic or associated with LV dysfunction [40].

●MVP characteristics – Patients with severe myxomatous leaflet remodeling are considered at increased risk of ventricular arrhythmias [44,45]. Bileaflet prolapse is often associated with severe myxomatous disease, but isolated bileaflet prolapse is not a harbinger of SCD [64].

●Mitral annular disjunction – Patients with MAD associated with MVP are considered at heightened risk of ventricular arrhythmia, although the clinical significance of MAD remains controversial [45,46,65,66]. The incidence of ventricular arrhythmias in patients with MAD is modest, and MAD, in and of itself, is not linked to excess mortality [66]. MAD has also been described in patients who are not diagnosed with MVP and is also associated with ventricular arrhythmias in this context [65].

●ECG findings – Electrocardiographic (ECG) repolarization abnormalities are often located in the inferior territory and are more frequent in patients who present with arrhythmias [44].

The presence of frequent and/or polymorphic ventricular extrasystole originating in the perimitral region is often observed on routine ECG in patients who later present with more severe ventricular arrhythmias or SCD [45].

●Myocardial fibrosis by CMR – CMR enables identification of myocardial fibrosis by late gadolinium enhancement (LGE). LGE detected around the mitral apparatus, annulus, posterior wall, and papillary muscles is considered as a mechanistic factor yielding ventricular arrhythmias [16,67].

CMR is indicated in patients with suboptimal echocardiographic assessment of MVP, MR, and MAD, as discussed separately. (See "Mitral valve prolapse: Clinical manifestations and diagnosis", section on 'Cardiovascular magnetic resonance'.)

The following additional indications for CMR have been proposed but are not established [41]:

•For patients with MVP who have survived cardiac arrest or have experienced sustained VT prior to implantable cardioverter-defibrillator (ICD) implantation.

•For patients with MVP and unexplained syncope and/or nonsustained VT.

Serial monitoring — Serial monitoring suggested for patients with MVP and significant MR includes echocardiography and ambulatory ECG monitoring [41]. The role of ILR in patients with MVP is not well-defined.

The combination of the above factors is essential in defining the intensity of monitoring for arrhythmias. As examples:

●Ambulatory monitoring is not required for patients with MVP, mild MR, and no symptoms or infrequent palpitations.

●A patient with MVP and palpitations should have ambulatory monitoring for diagnosis of the cause and frequency of arrhythmias. (See "Evaluation of palpitations in adults".)

●A patient with unexplained syncope, abnormal repolarization, MVP with severe myxomatous disease, polymorphic extrasystole, and myocardial fibrosis should have prolonged ambulatory monitoring and, possibly, ILR until ventricular arrhythmias are identified or effectively ruled out.

Categorizing ventricular arrhythmias — In patients with MVP, ventricular arrhythmias unexplained by other cause are thought to be related to the presence of MVP, although the possibility of a genetically linked separate etiology cannot be excluded [44].

Arrhythmias may be stratified as:

●None to minimal – Premature ventricular complexes/contractions (PVCs; also referred to as premature ventricular beats or premature ventricular depolarizations) <5 percent of heart beats by Holter monitoring and absence of more serious arrhythmias.

●Mild – Monomorphic isolated PVCs that are ≥5 percent of heart beats.

●Moderate – Polymorphic isolated PVCs or monomorphic NSVT of maximum rate <180 bpm and monomorphic.

●Severe – Sustained VT or NSVT at ≥180 bpm and/or polymorphic. MVP with severe ventricular arrhythmia is associated with excess subsequent mortality [44]. Management is based on the severity of the arrhythmia and whether there is associated severe MR. This syndrome was recognized by a consensus panel gathered by the European Heart Rhythm Association (EHRA) and endorsed by several cardiology societies [41].

●Immediate threat – Hemodynamically complicated sustained VT or ventricular fibrillation resulting in sudden cardiac arrest (SCA).

Role of electrophysiologic study — A role for electrophysiologic study in patients with MVP has not been defined [41]. Data regarding the value of programmed stimulation in patients with MVP are very sparse [68], and the consensus is that the clinical value of complex arrhythmias induced under these circumstances is subject to caution and rarely yields indications for ICD implantation [41].

Conversely, after ICD implantation for SCA and recurrent ventricular fibrillation, electrophysiologic determination of the site and mechanism of recurrent arrhythmias is useful for radiofrequency ablation [41]. Similarly, programmed ventricular stimulation in a high proportion of patients with frequent PVCs/VT and MAD enables identification of the mitral annular origin of arrhythmias and successful ablation of the responsible foci [69]. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Programmed electrical stimulation'.)

Management of ventricular arrhythmias — The therapy indicated is based on the severity of the arrhythmia and its association to severe MR. The following approach is in broad agreement with the EHRA expert consensus statement, which addresses the following categories [41]:

●MVP with SCA or sustained VT – Survivors of SCA or sustained VT without a clearly reversible cause are considered to be at high risk for subsequent SCA. Indication for ICD with secondary consideration for VT ablation in case of recurrent appropriate discharge of the device. Standard recommendations for ICD implantation apply to patients with MVP and either SCA or sustained VT, as discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

Depending on the severity of MR, mitral valve repair may be indicated before or after ICD implantation. For patients with high-risk VT and severe primary MR, mitral valve intervention may reduce the risk of ventricular arrhythmias, but the efficacy of this approach has not been established. Indications for mitral intervention are discussed separately. (See "Chronic primary mitral regurgitation: Indications for intervention".)

●MVP with heart failure and LV ejection fraction ≤35 percent – The standard indication for ICD for primary prevention of SCD is applicable to patients with MVP. However, the indication is for patients with symptomatic heart failure with LV ejection fraction (LVEF) ≤35 percent despite three months of optimal medical therapy, as discussed separately, and such a low LVEF is rare among patients with MVP. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)

●Severe MR and NSVT – In patients with NSVT and severe MR treated with mitral valve intervention, the role of adjunctive ICD implantation or VT ablation has not been defined [41]. General indications for intervention in patients with MVP and MR are discussed separately. (See "Chronic primary mitral regurgitation: Indications for intervention" and "Acute mitral regurgitation in adults".)

In observational studies, surgical correction of MR in patients with MVP was associated with reduced all-cause mortality in patients with MVP and MR [12] and reduced incidence of SCD in patients with flail mitral leaflet [40]. However, the efficacy of mitral valve repair or replacement in reducing the risk of SCD in patients with severe MR and ventricular arrhythmias has not been established.

●PVC-induced cardiomyopathy – PVC-induced cardiomyopathy is presumed in a patient with high burden of PVCs (ie, >15 percent) and LVEF <50 percent. Management, including beta blockers, ablation, and antiarrhythmic therapy, is discussed separately. (See "Premature ventricular complexes: Treatment and prognosis", section on 'Premature ventricular complex cardiomyopathy'.)

●MVP with mild or moderate arrhythmia – Frequent Holter monitoring or ILR is suggested depending on the baseline arrhythmias and phenotype of the MVP. (See "Ambulatory ECG monitoring".)

●MVP with no arrhythmia – If symptoms such as unexplained presyncope or syncope develop, evaluation commonly includes ambulatory ECG (Holter) monitoring, as discussed separately. (See "Syncope in adults: Risk assessment and additional diagnostic evaluation".)

While the EHRA expert consensus statement suggested periodic Holter monitoring for individuals with MVP and no symptoms [41], the clinical utility and frequency of such monitoring has not been defined.

INFECTIVE ENDOCARDITIS — Despite the risk of infective endocarditis (IE) in patients with MVP and mitral regurgitation (MR), routine antibiotic prophylaxis is not indicated for these patients (in the absence of history of IE or prior valve repair or replacement) [9,10,70]. Preventive measures for patients with MVP include maintenance of oral hygiene and timely treatment of any infections with pathogens that cause endocarditis. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

This approach is justified by the rarity (37 percent) of cases of IE on MVP in which the point of entry can be defined [71] and the low incidence of IE in patients with MVP. Indeed, while the risk of IE is higher with MVP than with a normal mitral valve, the absolute risk of infection is low. A population-based study of 896 adults with MVP found that the 15-year risk of IE was 1.1 percent (86.6 cases per 100,000 person-years) [72]. The age- and sex-adjusted relative risk of IE in patients with MVP was 8.1 (95% CI 3.6-18.0) compared with the general population. The incidence of IE was higher in patients with moderate or greater MR (289.5 cases per 100,000 years) compared with patients with less than moderate MR (63.3 cases per 100,000 person-years). No IE cases were identified in patients without previously diagnosed MR. Although data were limited, the risk of IE was higher in patients with flail mitral leaflet (715.5 cases per 100,000 person-years).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Cardiac valve disease".)

SUMMARY AND RECOMMENDATIONS

●Complications of MVP – Complications in patients with mitral valve prolapse (MVP) include mitral regurgitation (MR), heart failure, left atrial (LA) dilation with atrial fibrillation (AF), infective endocarditis (IE), ventricular arrhythmias, and, rarely, sudden cardiac death (SCD). The time course of complications is variable. (See 'Introduction' above and 'Time course' above.)

●Mitral regurgitation – Outcomes in patients with MVP are largely determined by the presence and severity of MR. Monitoring and management of MR are discussed separately. (See "Chronic primary mitral regurgitation: General management" and "Chronic primary mitral regurgitation: Indications for intervention".)

●Heart Failure – Heart failure in patients with MVP is primarily related to the severity of MR but is also influenced by other complications (eg, left ventricular [LV] dysfunction or AF). In patients with heart failure caused by MR, medical treatment is only temporizing in preparation for mitral valve intervention. (See 'Importance of mitral valve intervention' above and "Chronic primary mitral regurgitation: Indications for intervention".)

●Ischemic neurologic events – Ischemic neurologic events complicating MVP are mostly due to concurrent conditions, such as AF, and mitral surgery. Ischemic neurologic events are rare in patients with uncomplicated MVP. For patients with MVP without history of thromboembolic events, AF, or mitral surgery, routine antithrombotic therapy is not required. (See 'Ischemic neurologic events' above.)

Antithrombotic therapy after mitral valve surgery (repair or replacement) is discussed separately. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair" and "Antithrombotic therapy for mechanical heart valves".)

●LA dilation and AF – In patients with MVP and MR, marked LA dilation is associated with subsequent excess mortality and risk of AF. The occurrence of AF is associated with adverse outcomes and warrants prompt consideration of mitral intervention. (See 'Risk of atrial fibrillation' above and 'Management of atrial fibrillation' above and "Chronic primary mitral regurgitation: Indications for intervention".)

●Risk stratification for SCD – The risk of sudden cardiac arrest or ventricular arrhythmia is increased in patients with MVP with one or more high risk features: unexplained syncope, at least moderate to severe MR, repolarization abnormalities or ventricular arrhythmias on ECG, severe myxomatous mitral leaflet degeneration, mitral annular disjunction, or late gadolinium enhancement (LGE) of the papillary muscles or periannular area on cardiovascular magnetic resonance (CMR) imaging. The role of rhythm monitoring is determined by the presence of risk factors. (See 'Risk stratification for SCD and ventricular arrhythmias' above.)

●Management of ventricular arrhythmias

•SCA or sustained VT – For patients with MVP with prior sudden cardiac arrest or sustained ventricular tachycardia (VT), standard recommendations for implantable cardioverter-defibrillator (ICD) implantation apply, as discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

Depending on the severity of MR, mitral valve repair may be indicated before or after ICD implantation. For patients with high-risk VT and severe primary MR, mitral valve intervention may reduce the risk of ventricular arrhythmias, but the efficacy of this approach has not been established. Indications for mitral intervention are discussed separately. (See "Chronic primary mitral regurgitation: Indications for intervention".)

•Primary prevention of SCD – The standard indication for ICD for primary prevention of SCD applies to patients with MVP. However, the indication is for patients with symptomatic heart failure with LV ejection fraction (LVEF) ≤35 percent despite three months of optimal medical therapy, as discussed separately, and such a low LVEF is rare among patients with MVP. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".)

●Infective endocarditis – Although patients with MVP and MR are at risk for developing IE, routine antibiotic prophylaxis is not indicated for these patients (in the absence of history of IE or prior valve repair or replacement). (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Sorin Pislaru, MD, and Matthew Sorrentino, MD, who contributed to earlier versions of this topic review.

The UpToDate editorial staff also acknowledges William H Gaasch, MD (deceased), who contributed to earlier versions of this topic.