A 75-year-old man was referred to the cardiology clinic for evaluation of fatigue in the setting of mild to moderate mitral regurgitation and right ventricular (RV) enlargement on transthoracic echocardiography (TTE). Cardiac magnetic resonance imaging was obtained to further assess RV size and demonstrated normal RV dimensions with reduced biventricular systolic function, as well as MAD associated with moderate bileaflet MVP (Figure 1). In retrospect, TTE demonstrated the Pickelhaube sign (Figure 2). No late gadolinium enhancement was identified. Ambulatory Holter monitoring revealed no ventricular arrhythmias.

This patient with mild-to-moderate mitral regurgitation and no definitive echocardiographic evidence of MVP underwent CMR, which identified MAD and bileaflet prolapse. This case underscores the clinical challenges in determining when patients with suspected or subtle echocardiographic findings should undergo advanced imaging, as well as identifying asymptomatic phenotypes that warrant further arrhythmic risk stratification. In this instance, concern for right ventricular dysfunction prompted CMR, which revealed MAD and bileaflet prolapse as phenotypic risk factors for ventricular arrhythmias. Given these findings, a strategy of surveillance for ventricular ectopy was pursued despite the absence of symptoms or documented clinical events.

A 45-year-old man with a history of asymptomatic MVP and a family history of SCD in multiple paternal relatives was referred to the cardiology clinic for evaluation of palpitations. Ambulatory Holter monitoring revealed nonsustained ventricular tachycardia (Figure 3), and CMR demonstrated mild bileaflet MVP associated with MAD and trace mitral regurgitation. No late gadolinium enhancement was identified. An electrophysiology study did not induce ventricular arrhythmias; therefore, an implantable cardioverter-defibrillator was not placed. An implantable loop recorder was subsequently placed for long-term monitoring of ventricular arrhythmias. After 18 months of continuous monitoring, no ventricular arrhythmias have been detected.

This patient transitioned from asymptomatic to symptomatic MVP with the development of palpitations and associated nonsustained ventricular tachycardia, in the context of a family history of SCD affecting multiple relatives. Cardiac magnetic resonance imaging identified bileaflet MVP and MAD as high-risk phenotypes. Compared with Case 1, this patient was considered to be at higher risk; accordingly, identification or provocation of malignant ventricular arrhythmias would have prompted consideration of a secondary-prevention implantable cardioverter-defibrillator.

A 48-year-old woman with a history of mitral regurgitation and symptomatic ventricular ectopy originating from the posteromedial papillary muscle was referred to the cardiology clinic because of concern for symptoms associated with a severe mitral regurgitation murmur that appeared discrepant with TTE findings of only moderate mitral regurgitation. Six years earlier, she had been evaluated by electrophysiology for symptomatic ventricular ectopy in the setting of CMR demonstrating late gadolinium enhancement of the papillary muscles and submitral valvular apparatus, and she had declined catheter ablation at that time.

She now presented with exertional exercise intolerance and palpitations. Repeat CMR demonstrated moderate-to-severe mitral regurgitation with mildly reduced left ventricular ejection fraction, MAD, and persistent papillary and subvalvular inferolateral late gadolinium enhancement (Figure 4). In retrospect, MAD had also been present on TTE performed 14 months earlier at an outside institution (Figure 5). Cardiopulmonary exercise testing objectively confirmed reduced exercise tolerance.

This patient initially presented with symptomatic ventricular ectopy and subsequently developed progressive mitral regurgitation in the setting of known perivalvular late gadolinium enhancement and previously unrecognized MAD identified retrospectively six years earlier. Although she had not experienced clinical or subclinical malignant ventricular arrhythmias, she represented a high-risk phenotype characterized by severe mitral regurgitation, ventricular ectopy, reduced left ventricular ejection fraction, and CMR evidence of MAD and late gadolinium enhancement.

Because she met a Class I indication for mitral valve surgery, surgical intervention was pursued first, with the additional rationale of potentially reducing ongoing mechanical traction and progressive fibrosis that could contribute to ventricular ectopy. When her ectopic burden increased despite successful mitral valve surgery, targeted catheter ablation was subsequently offered.

A 48-year-old man with a history of atrial fibrillation and MVP presented to the hospital after an out-of-hospital cardiac arrest. He had witnessed a motor vehicle collision and was assisting those involved when he experienced syncope; emergency medical services found him in ventricular fibrillation on initial evaluation. He was successfully resuscitated with external defibrillation, mechanical ventilation, therapeutic hypothermia, and vasopressor support, and subsequently made a full neurological recovery.

Given initial concern for a primary channelopathy as the cause of his cardiac arrest, an electrophysiology study was performed. Polymorphic ventricular tachycardia was induced with epinephrine challenge without associated QT interval shortening, raising concern for catecholaminergic polymorphic ventricular tachycardia rather than congenital long QT syndrome. An implantable cardioverter-defibrillator was placed, and beta-blocker therapy was initiated. Genetic testing at that time was inconclusive. CMR demonstrated bileaflet MVP with mild-to-moderate mitral regurgitation.

Seven years later, the patient developed recurrent device therapies, including antitachycardia pacing and defibrillation, for monomorphic ventricular tachycardia. Transthoracic echocardiography redemonstrated bileaflet prolapse with possible MAD (Figure 6). Repeat CMR confirmed bileaflet prolapse with mitral regurgitation and additionally revealed prominent MAD and basal lateral left ventricular late gadolinium enhancement (Figure 7). Despite aggressive medical therapy for rhythm control, his ventricular tachycardia burden and device therapies continued to escalate, prompting referral for catheter ablation.

Given his prior electrophysiology study complicated by ventricular fibrillation, careful consideration was given to procedural planning to ensure hemodynamic stability during arrhythmia induction. During repeat electrophysiology study, sustained monomorphic ventricular tachycardia was successfully induced using standard pacing maneuvers. Given preserved hemodynamic stability, mapping focused on the basal lateral left ventricular wall corresponding to the region of late gadolinium enhancement. Surface electrocardiography demonstrated a right bundle branch block morphology with a superior axis and lead I negativity, consistent with this anatomic substrate. Entrainment mapping within areas of dense scar identified findings consistent with the clinical tachycardia exit site. Multiple radiofrequency ablation lesions were delivered using an irrigated catheter at 30 W, followed by escalation to 35 W targeting a 10-ohm impedance drop. Following ablation, repeat electrophysiology study demonstrated noninducibility of ventricular arrhythmias.

Subsequent genetic testing identified a likely pathogenic titin (TTN) gene variant, raising further questions regarding the patient’s initial diagnosis of catecholaminergic polymorphic ventricular tachycardia.

This patient initially presented with ventricular fibrillation arrest and inducible polymorphic ventricular tachycardia, which was initially characterized as catecholaminergic polymorphic ventricular tachycardia and congenital long QT syndrome following invasive testing. However, the subsequent development of breakthrough monomorphic ventricular tachycardia in the setting of known bileaflet MVP and mitral regurgitation on prior CMR and, in retrospect, previously unrecognized MAD, prompted reconsideration of the underlying mechanism. These findings raised concern for progressive mechanical traction and fibrosis resulting in scar-mediated ventricular tachycardia. Follow-up CMR confirmed this suspicion and guided successful percutaneous ventricular tachycardia ablation. Notably, prior genetic testing initially performed for suspected channelopathy ultimately revealed a mutation later identified as a pathogenic marker associated with arrhythmogenic MVP.

* Arrhythmogenic MVP is mediated by mechanical stretch from leaflet prolapse and MAD, which may result in electromechanical dispersion and/or replacement fibrosis, potentially exacerbated by adverse remodeling from progressive mitral regurgitation.

* Patients with MVP and structural heart disease on comprehensive echocardiography, or with clinical risk factors for arrhythmogenic MVP, should undergo early CMR, which is critical for identifying MAD and late gadolinium enhancement as risk factors for ventricular arrhythmias.

* Detection of ventricular arrhythmias through ambulatory Holter monitoring, continuous rhythm monitoring, or provocation during electrophysiology study further refines risk stratification and informs candidacy for primary-prevention implantable cardioverter-defibrillator implantation and/or aggressive medical or ablative therapy.