7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Arrhythmic complications of mitral valve prolapse : Matthew J Sorrentino, MD, FACC : Catherine M Otto, MD, Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 02, 2021. INTRODUCTION Mitral valve prolapse (MVP) is the most common cause of primary mitral regurgitation (MR) in developed countries. The diagnosis is usually suspected from cardiac auscultation and then confirmed by echocardiography. (See "Mitral valve prolapse: Clinical manifestations and diagnosis".) Although the correlation between certain nonspecific symptoms and MVP remains unclear, many patients with this disorder present with palpitations and atrial or ventricular arrhythmias [1-5]. Some studies suggest that these patients are at increased risk of sudden cardiac death (SCD) compared with the general population, but the exact incidence is unknown. Furthermore, since atrial and ventricular arrhythmias are common in the general population, it is not clearly established that the incidence of arrhythmias and SCD are in fact increased in patients with MVP. This topic will review the incidence of arrhythmias, the risk of SCD, the electrocardiographic abnormalities that can be seen, and the treatment of arrhythmias in patients with MVP. The nonarrhythmic complications of MVP, including nonspecific symptoms and major complications, such as infective endocarditis, MR, transient ischemic attacks, and cerebrovascular accidents, are discussed separately. (See "Nonarrhythmic complications of mitral valve prolapse" and "Mitral valve prolapse syndrome".) PREVALENCE OF ARRHYTHMIAS https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 1/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Several studies report a broad range in -prevalence of the arrhythmias in patients with MVP [1- 5]: Premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) 35 to 90 percent. Paroxysmal supraventricular tachycardia 3 to 32 percent. Ventricular premature beats 58 to 89 percent. Complex ventricular ectopy 30 to 56 percent. This wide variability is most likely due to selection bias and to the heterogeneity of the populations studied. Most studies have been performed in adults, but ventricular arrhythmias have also been reported in children with MVP [6,7]. What remains unclear is whether the prevalence of one or more of these arrhythmias in adults with MVP is higher than in controls. Some well-controlled studies do not show an increased prevalence of arrhythmias in MVP. The Framingham Heart Study compared 84 patients with MVP, based upon current two-dimensional echocardiographic criteria, with 3403 control subjects without MVP [8]. On average, the patients in this study had trace to mild mitral regurgitation (MR). The prevalence of atrial ectopy (3.2 versus 1.6 percent), atrial fibrillation (1.2 versus 1.7 percent), and ventricular ectopy (2.6 versus 1.4) was equivalent in the two groups. This study suggests that MVP without significant MR is not associated with excess risk of atrial or ventricular arrhythmias. Arrhythmias may be more common in patients with MVP who develop MR, a population that may be overrepresented in some studies [9]. Patients with MR and MVP have more ventricular arrhythmias than those with MVP alone [10]. The presence of moderate to severe MR is an independent predictor of ventricular arrhythmias in patients with MVP [11]; in this setting, ventricular arrhythmias are associated with significant mitral valve annular abnormalities and left ventricular dysfunction [12]. Atrial arrhythmias are also more common in those with MVP and MR than in those with MVP alone [10]. The presence of moderate to severe MR is an independent predictor of atrial arrhythmias in patients with MVP [13]. In echocardiographic series of patients with MVP, the observed frequency of atrial fibrillation (AF) has varied from 1 to 25 percent or more [14]. 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 13 percent. Risk factors for development of AF were evaluated in 89 patients with moderate to severe MR and simple MVP and 360 patients with flail mitral leaflets [15]. In both groups, the predictors of AF were age and left atrial diameter. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 2/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate SUDDEN CARDIAC DEATH SCD in patients with MVP is usually due to ventricular fibrillation [16]. However, the relation between MVP and SCD is uncertain. Consistent with a causative role for MVP is the observation that MVP is the only cardiac abnormality in some patients at autopsy and in certain survivors of SCD [16-23]. As an example, among a cohort of 24 patients with an implantable cardioverter- defibrillator who experienced idiopathic out-of-hospital cardiac arrest (all had no evidence of myocardial ischemia, cardiomyopathy, or channelopathy), 10 patients (42 percent) were found to have bileaflet MVP [23]. Patients with MVP in this cohort were also significantly more likely to have T wave abnormalities and ventricular ectopy compared with those with normal mitral valves. (See 'Electrocardiographic abnormalities' below.) MVP is also the only cardiac abnormality found in 8 to 16 percent of patients with refractory ventricular tachycardia (VT) [1-3]. On the other hand, both SCD and VT can occur in patients without apparent structural heart disease, and it is not clear that other causes of SCD and VT were excluded in the above reports. (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".) The incidence of SCD in patients with MVP is not clearly established. One estimate of the risk of SCD in patients with MVP without MR was 1.9 per 10,000 patients per year [1]. The risk was estimated to be 50 to 100 times higher (0.9 to 1.9 percent per year) if significant MR is present; this is the rate that was later observed in patients with flail mitral leaflet (see 'Flail mitral leaflet' below). In series including patients with MVP with a spectrum of MR severity, an intermediate risk of SCD has been observed. Two such series of 237 and 300 patients, both with mean follow- up of six years, found that SCD occurred in 2.5 and 1.0 percent (0.4 and 0.2 percent per year), respectively [20,21]. Early small series of patients with MVP suggested an association between the following factors and increased risk of SCD [1-3,18,24]: history of syncope or near syncope, symptoms such as palpitations, chest pain, and dyspnea, prolonged QT interval or inferolateral repolarization abnormalities, frequent or complex ventricular premature beats, prolapse of both the anterior and posterior mitral valve leaflets, hemodynamically significant mitral regurgitation, and flail mitral leaflet. The increased risk of SCD associated with flail mitral leaflet was confirmed in a large series [25]. (See 'Flail mitral leaflet' below.) A study of 237 patients found a higher incidence of SCD (approximately 1.6 percent per year) in patients with redundant (defined as thickness of 5 mm or more) mitral valve leaflets as https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 3/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate compared with the rate (approximately 0.1 percent per year) for those without redundant leaflets [20]. The increased risk of SCD associated with MR may be directly related to the valvular regurgitation, rather than MVP itself. (See "Chronic primary mitral regurgitation: General management".) Proposed pathophysiologic mechanisms for SCD include fibrosis in the papillary muscles and inferobasal wall of the left ventricle, mitral annular disjunction, and systolic curling of the mitral leaflets [26]. Premature ventricular complexes (PVCs) arising from the Purkinje tissue may be a trigger for ventricular fibrillation [27]. Risk stratification As for other patient populations, prior cardiac arrest or sustained VT are strong predictors of SCD in individuals with MVP. While other clinical risk factors for sudden death, such as the presence of flail leaflet or the presence of significant mitral regurgitation, have been proposed, no specific recommendations for risk stratification of patients with MVP have been defined. The 2017 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines for ventricular arrhythmias and SCD recommended that patients with valvular heart disease and ventricular arrhythmias should be evaluated and treated following current recommendations for each disorder [28]. No specific risk stratification of patients with MVP for SCD was recommended. Flail mitral leaflet Among patients with MVP, SCD appears be more common in patients with chordal rupture resulting in a flail mitral leaflet, particularly those treated conservatively. (See "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet".) The following findings were noted in a retrospective report of 348 patients with flail mitral leaflet who were followed for a mean of four years [25]: The estimated sudden death rate at 5 and 10 years was 8.6 and 18.8 percent, respectively. The linearized rate was 1.8 percent per year. Independent predictors of sudden death were New York Heart Association class III and IV (7.8 versus 1.0 and 3.1 percent per year in class I and II, respectively), left ventricular ejection fraction (LVEF) less than 50 percent (12.7 versus approximately 1.2 percent with LVEF above 50 percent), and atrial fibrillation (4.9 versus 1.3 percent per year with sinus rhythm). https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 4/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Twenty percent of patients with sudden death had none of these risk factors; the yearly rate of sudden death in this setting was 0.8 percent. Other comorbidities prevalent in these patients may have been important. Surgical correction of the flail leaflet reduced the incidence of sudden death (adjusted hazard ratio 0.29). Causes of sudden cardiac arrest generally are discussed separately. (See "Pathophysiology and etiology of sudden cardiac arrest".) ELECTROCARDIOGRAPHIC ABNORMALITIES Several electrocardiographic abnormalities have been reported in patients with MVP, including QT interval prolongation, repolarization abnormalities, and evidence for accessory pathways. These findings, however, are not supported by all surveys of patients with MVP. As an example, some studies report that as many as 75 percent of patients with MVP have QT interval prolongation [1]. In contrast, at least two series found no increase in QT prolongation compared with control populations [1,29]. The Framingham Heart Study found no difference in the prevalence of left ventricular hypertrophy or left atrial enlargement between those with and without MVP [8]. There is also no evidence to indicate an increased prevalence of accessory pathways in patients with MVP. In addition, the claim that ST segment and T wave abnormalities are more common in MVP is controversial, as is the possible link between repolarization abnormalities and arrhythmias. One study noted greater dispersion of refractoriness in 32 patients with MVP and documented ventricular arrhythmias, although the QT interval was not prolonged [30]. This raises the possibility that regional shortening and lengthening of repolarization times may be a mechanism for arrhythmias and SCD in MVP. CMR In a cardiovascular magnetic resonance (CMR) imaging report, focal late gadolinium enhancement (LGE) in the papillary muscles was observed in patients with MVP, particularly in those with complex ventricular arrhythmias [31]. LGE at the level of the papillary muscles and inferobasal wall of the left ventricle was found in a population of MVP patients with ventricular arrhythmias, suggesting a possible correlation with histologic findings of fibrosis in some patients with MVP and SCD [32]. The clinical significance of these CMR findings has not been determined. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 5/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate ELECTROPHYSIOLOGIC TESTING Electrophysiologic (EP) testing has been used in an attempt to understand the role of arrhythmias in patients with MVP. Unfortunately, the data are again conflicting. It has been suggested that patients with symptoms or documented arrhythmias are more likely to have inducible ventricular tachycardia. However, an analysis of six fairly rigorous studies found that only 6 out of 100 patients with symptomatic or asymptomatic nonsustained ventricular tachycardia had inducible sustained monomorphic ventricular tachycardia; as a result, the association between inducibility and clinical symptoms is unlikely to be valid [33]. Similar to its role in other patient groups, EP testing is not generally performed in survivors of SCD or sustained ventricular tachycardia. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'EP study'.) MANAGEMENT The treatment of arrhythmias in patients with MVP varies with the clinical setting. Survivors of SCD or sustained VT Survivors of SCD or sustained ventricular tachycardia with structural heart disease are considered to be at high risk for subsequent SCD. An implantable cardioverter-defibrillator is recommended in such patients. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Very symptomatic palpitations The type and presence of arrhythmias in patients with marked symptoms due to palpitations should be documented by either 24-hour Holter or transtelephonic monitoring. Treatment is then initiated based upon both the arrhythmia and the severity of symptoms. The benefit derived from the relief of symptoms with treatment must be weighed against the possible proarrhythmic and other side effects of many antiarrhythmic drugs. (See "Evaluation of palpitations in adults".) Mild palpitations from atrial or ventricular premature beats Many patients with mild palpitations from premature beats can be treated conservatively with reassurance, abstinence from alcohol or stimulants such as caffeine or nicotine, and participation in an exercise program. Beta blockers can occasionally be used; they are particularly effective in patients with inappropriate heart rate responses to stress, anxiety, or activity. (See "Premature ventricular complexes: Treatment and prognosis".) Atrial fibrillation As mentioned above, it is not clear if the incidence of atrial fibrillation (AF) is increased in patients with MVP who have no or mild mitral regurgitation (MR) [8]. The risk of https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 6/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate AF is related to MR, age, and atrial size. The role of antithrombotic therapy in patients with MVP with and without AF is presented separately. (See "Chronic primary mitral regurgitation: General management".) In addition, the development of new-onset AF in patients with MVP and severe MR is an indication for corrective surgery. (See "Indications for intervention for chronic severe primary mitral regurgitation".) Asymptomatic patients without evidence of sustained arrhythmias There is no evidence that therapy will offer any survival advantage to asymptomatic patients without evidence of sustained arrhythmias. The prognosis in asymptomatic patients with nonsustained arrhythmias and structurally normal hearts is quite good. Thus, the potential deleterious effects of drug therapy probably outweigh any risk from the arrhythmia in this setting. Mitral valve surgery Although there is a risk of SCD in patients with MVP, particularly among those with flail mitral leaflet treated conservatively, the efficacy of mitral valve repair or replacement in reducing the risk of sudden death in patients with severe MR and ventricular arrhythmias is not well established [34]. Indications for surgery in patients with MVP and MR are discussed separately. (See "Indications for intervention for chronic severe primary mitral regurgitation" and "Acute mitral regurgitation in adults".) Participation in sports Recommendations for participation in sports for patients with MR are detailed separately. (See "Chronic primary mitral regurgitation: General management", section on 'Exercise'.) 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 Atrial and ventricular arrhythmias have been observed in patients with mitral valve prolapse (MVP). However, there is evidence that the prevalence of these arrhythmias is https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 7/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate similar to that in the general population, at least among those with trace or mild mitral regurgitation. (See 'Prevalence of arrhythmias' above.) The risk for sudden cardiac death (SCD) in patients with MVP appears to vary with severity of accompanying mitral regurgitation. (See 'Sudden cardiac death' above.) 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ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 10/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006; 48:e247. Topic 8169 Version 23.0 Contributor Disclosures Matthew J Sorrentino, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Catherine M Otto, MD No relevant financial relationship(s) with ineligible companies to disclose. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 11/11