Malignant Mitral Valve Prolapse With Life-Threatening Ventricular Arrhythmias

Abstract

Clinical Condition

A 45-year-old woman with long-standing bileaflet myxomatous mitral valve prolapse (MVP), mitral annular disjunction, and mild mitral regurgitation (MR) developed near-syncope and was found to have frequent polymorphic ventricular tachycardia on ambulatory monitoring. Despite medical therapy, she experienced recurrent ventricular fibrillation and multiple implantable cardioverter-defibrillator (ICD) shocks.

Key Questions

Can malignant arrhythmogenic MVP occur in the absence of severe MR or detectable myocardial fibrosis on cardiac magnetic resonance imaging? Which combination of electrical and mechanical risk markers identifies patients at imminent risk for sudden cardiac death? Can early surgical correction of the mechanical substrate durably suppress ventricular arrhythmias?

Outcome

The patient underwent mitral valve repair. Since then, she has remained free of arrhythmias and ICD shocks.

Take-Home Messages

Malignant MVP can manifest with multifocal ventricular tachycardia independent of MR severity. Prophylactic ICD placement followed by definitive mitral valve repair reduces arrhythmic triggers and prevents sudden cardiac death.

Visual Summary

Case Presentation

A 45-year-old woman was referred to our cardiology clinic in January 2012 for evaluation of mitral valve prolapse (MVP), a diagnosis known to her since an early age but not recently investigated. She was asymptomatic and physically active, capable of walking on a treadmill at 4 mph (6.4 kph) without any symptoms (NYHA functional class I). She had no history of syncope. She was 160 cm tall with a weight of 67.1 kg (body mass index: 26.2 kg/m²).

Take-Home Messages

• •Malignant mitral prolapse may present with life-threatening ventricular arrhythmias, even with nonsevere mitral regurgitation.
• •Early identification through multimodality imaging and prophylactic intervention (eg, ICD implantation and MR repair) can effectively prevent sudden cardiac death.

Question 1: Are there any characteristic features of malignant MVP on cardiac auscultation?

On cardiac auscultation, a midsystolic click and a late systolic grade II/VI apical murmur were heard. Murmur increased to III/VI during Valsalva strain, features recognized in patients with MVP but not specifically associated with malignant MVP. The initial electrocardiogram showed a sinus rhythm with T-wave inversion in the inferolateral leads (Figure 1A) and isolated premature ventricular contractions (PVCs), associated with arrhythmogenic MVP.¹

Figure 1.

Electrocardiograms Before and After Mitral Valve Repair

(A) Electrocardiogram at the patient's initial visit demonstrated sinus rhythm with T-wave inversion (arrows) in the inferolateral leads and isolated premature ventricular contractions. (B) Electrocardiogram after mitral valve repair demonstrated normal T waves (arrows). (C) ST-segment changes during exercise before mitral valve repair. (D) No ST-segment changes during exercise after mitral valve repair and cryoablation of pap muscle.

Question 2: Are there any echocardiographic features that help identify malignant MVP?

Transthoracic echocardiography revealed myxomatous mitral leaflets with bileaflet MVP (Barlow valve), mitral annular disjunction (MAD) with mild mitral regurgitation (MR), mild basal septal hypertrophy (11 mm), and severe left atrial (LA) dilation (Figure 2).

Visual Summary.

Malignant Mitral Valve Prolapse Phenotype

ICD = implantable cardioverter-defibrillator; MVP = mitral valve prolapse; SCD = sudden cardiac death.

Figure 2.

2-Dimensional/Doppler Echocardiography During Initial Visit (April 2015)

(A and B) Parasternal long-axis views demonstrating thickened mitral leaflet (asterisk), bileaflet prolapse (yellow arrows), dilated left atrium, mitral annular disjunction (red arrow), and basal septal hypertrophy (yellow arrowheads). (C) Parasternal short-axis view demonstrating myxomatous leaflet (arrows). (D) Apical 4-chamber view showing dilated left ventricle (diameter: 5.9) and large left atrium (volume index: 53). (E) Color-flow Doppler demonstrating late systolic jet of mitral regurgitation. (F) Continuous-wave Doppler documenting late systolic mitral regurgitation (arrowheads). (G) Pulsed-wave Doppler of posterolateral annulus demonstrating tall pickelhaube spike (28 cm/s). (H) Pulsed-wave Doppler of mitral inflow (E = 0.9, A = 0.5). (I) Pulsed-wave Doppler of septal mitral annulus (e′ = 5 cm/s). LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

Echocardiographic strain imaging revealed supranormal longitudinal strain localized to the posterolateral left ventricular wall at the basal and mid levels, with relative septal reduction (trident pattern), indicating high workload. Tissue Doppler imaging demonstrated a prominent pickelhaube spike at the lateral mitral annulus.

Speckle-tracking echocardiography was published by Muthukumar et al.² They illustrated that supranormal longitudinal strain (>24%) consistently localizes to the posterolateral left ventricular wall, forming a “trident” pattern, whereas the basal septum often shows reduced strain (<18%). This mechanical heterogeneity demonstrates regional myocardial overload, mostly due to systolic tugging of the posterolateral wall by the papillary muscle and prolapsing leaflets. Hence, this segment of the posterolateral wall is consistently subjected to a high workload, which may eventually lead to fibrotic substrate and perpetuated arrhythmogenesis. The pickelhaube (spiked helmet) sign, a spiked systolic velocity pattern observed on tissue Doppler imaging of the lateral mitral annulus, represents abrupt systolic motion due to excessive leaflet prolapse, MAD, and annular hypermotility. In arrhythmogenic MVP, this sign reflects the forceful systolic tugging and curling of the posterolateral wall, papillary muscles, and the prolapsing mitral valve leaflets.²

Question 3: What is the role of cardiac magnetic resonance imaging in identifying arrhythmogenic MVP?

In our case, cardiac magnetic resonance imaging (CMR) demonstrated bileaflet myxomatous MVP with MAD, mild MR, and moderate LA enlargement, with no evidence of papillary muscle scar or delayed myocardial enhancement.

Advanced imaging modalities such as CMR are powerful tools for further phenotyping and tissue characterization in MVP. Late gadolinium enhancement (LGE) on CMR is a key sign of replacement myocardial fibrosis and has been consistently linked with malignant MVP. A pattern of midmyocardial LGE is typically seen in the basal inferolateral wall and is thought to be secondary to chronic mechanical stress from prolapsing leaflets and MAD, or in the papillary muscle. Patients with MVP and LGE have been shown to have more complex ventricular ectopy.³ Additionally, with parametric mapping, CMR can show interstitial fibrosis, which can be demonstrated with elevated native T1 values and extracellular volume or myocardial edema with elevated T2 values.⁴ However, the absence of detectable fibrosis on CMR does not exclude risk, and sudden cardiac death (SCD) has been documented in the absence of detectable enhancement, indicating that the mechanical arrhythmogenic mechanisms may precede fibrotic remodeling, as in our patient.¹ Beyond LGE and parametric mapping, CMR can provide detailed anatomical and function information on ventricular volumes, systolic function, valve anatomy, degree of MR, areas of hypertrophy, and MAD, especially for patients in whom echocardiographic imaging may be challenging.

Question 4: How should an asymptomatic patient with bileaflet MVP and mild MR be risk stratified?

Although most cases of MVP follow a benign course, patients with bileaflet prolapse, especially those with a Barlow-type valve characterized by diffuse myxomatous leaflet thickening and redundancy and associated electromechanical abnormalities, can present with complex ventricular arrhythmias and heightened risk of SCD,⁵ with an estimated annual risk of 0.2% to 0.4%, which is 3-fold higher than in the general population.^6,7

The pathogenesis of arrhythmogenic MVP is multifactorial, consisting of structural, mechanical, and electrophysiological contributors. Myxomatous leaflets with a thickness of ≥5 mm and bileaflet involvement represent morphologic features in malignant MVP.^6,8 Also, the arrhythmic phenotype is frequently accompanied by MAD, a spatial separation between the mitral annulus and the basal left ventricular myocardium, which is particularly prevalent in Barlow-type valves and is seen in up to 55% of bileaflet MVP cases.⁵ MAD contributes to paradoxical annular dynamics, systolic curling, basal localized inferolateral wall hypertrophy, and abnormal systolic motion of the mitral apparatus, linked to ventricular arrhythmias independent of MR severity.¹ In the current case, although MR was mild, the constellation of bileaflet prolapse, MAD, inferolateral T-wave inversion, and pickelhaube sign raised early concern for arrhythmogenic phenotype despite absence of fibrosis.

Question 5: Does near-syncope in MVP represent benign autonomic dysfunction or malignant arrhythmia?

The clinical challenge lies in identifying which MVP patients are at high risk. Classical electrocardiographic clues, including inferolateral T-wave inversion, QT prolongation, and increased QT dispersion, have been observed in 33% to 78% of patients with malignant MVP; however, they are not pathognomonic.^3,9 Although PVCs are seen in up to 85% of the MVP population, malignant MVP is often associated with polymorphic or pleomorphic ventricular tachycardia (VT), frequently initiated by PVCs arising from the papillary muscles, left ventricular outflow tract (LVOT), or fascicular system.

At a routine follow-up in July 2013, the patient reported a near-syncopal episode while driving, without associated palpitations, chest pain, or dyspnea. Ambulatory Holter monitoring revealed 13 runs of polymorphic VT, including 1 highly disorganized short episode. Sinus rhythm with rare PVCs was also documented. The multidisciplinary team reviewed the findings and concluded that her arrhythmia burden was disproportionate to MR severity. Although tilt-table testing was negative and exercise tolerance was preserved, the presence of polymorphic VT shifted concerns toward arrhythmogenic MVP rather than neurocardiogenic syncope. Beta-blocker therapy was initiated.

Question 6: Should implantable cardioverter-defibrillator placement be considered despite nonsevere MR and absence of LGE?

By 2015, the patient's MR had progressed to moderate severity, while malignant ventricular arrhythmia had already emerged in the setting of nonsevere regurgitation. Given the potentially life-threatening arrhythmia burden, her beta-blocker dosage was increased, and she was referred to our electrophysiologist for consideration of implantable cardioverter-defibrillator (ICD) placement (Figure 1). The electrophysiologist deemed her at elevated risk for arrhythmogenic SCD based on multiple high-risk electrical and mechanical features, despite the absence of LGE on CMR.

Arrhythmogenic MVP exists along a pathophysiologic spectrum, from early mechanical and electrical triggers to later-stage structural myocardial remodeling and fibrosis. In this situation, ventricular ectopy and electrical instability arise from repetitive mechanical stress at the leaflet-annular-papillary muscle interface, whereas myocardial fibrosis detected by LGE demonstrates a subsequent manifestation of malignant arrhythmias.¹ ICD implantation was proposed, but catheter ablation was also considered because of the possibility of Purkinje fiber–triggered arrhythmia. However, varying PVC morphologies on Holter monitoring made a single ectopic focus unlikely. Catheter ablation may be effective in patients with a consistent ectopic focus. However, its utility is limited in polymorphic arrhythmias or those with multifocal PVCs. ICD remains the mainstay for secondary prevention, but current guidelines lack specific criteria for primary prevention in MVP.

The ICD was implanted for the patient in August 2015.

Question 7: Why did arrhythmias persist despite ICD and medical therapy?

Subsequently, in August 2015, the patient experienced 2 VT episodes necessitating appropriate ICD shocks. Remote interrogation of the first episode confirmed ventricular fibrillation after bradycardia and PVC-induced degeneration. A second VT event occurred 2 weeks later, with a cycle length of 190 to 230 ms and 3 different PVC morphologies noted. A brief nonsustained episode of VT was also captured (Figure 3). At this point, the multidisciplinary team revisited the potential underlying mechanism: repetitive systolic traction at the leaflet-annulus–papillary muscle interface.

Figure 3.

Morphology and Ventricular Ectopy of Premature Ventricular Contractions

(A) The morphology of the isolated premature ventricular contractions with right bundle branch block pattern in lead V₁ with R/S transition to V₃ and V₄, with a northwest axis in the limb leads. The morphology shows the origin close to the posteromedial papillary muscle region. (B) Intracardiac tracing from the implantable cardioverter-defibrillator demonstrating atrial and ventricular lead tracing. Sinus beat with normal atrioventricular conduction. The second beat is a premature ventricular contraction with coupling interval of 463 ms initiated in polymorphic ventricular tachycardia, degenerating into ventricular fibrillation.

Surgical mitral valve repair has long been recognized as a strategy for reducing arrhythmias in patients with bileaflet MVP, even in the absence of severe MR, by eliminating the leaflet and MAD-induced traction on the subvalvular myocardium.

At follow-up, the patient expressed anxiety about further ICD shocks. Psychiatric support was initiated, and multiple therapeutic strategies, including antiarrhythmics, sympathectomy, and mitral valve repair, were discussed. However, the patient declined surgical intervention.

Subsequently, she experienced 2 further ICD shocks for ventricular fibrillation during sleep, in September 2016 and October 2016.

Question 8: Should mitral valve repair for arrhythmogenic MVP be performed despite nonsevere MR and absence of scar burden on CMR?

This represented the pivotal decision point: The patient with myxomatous bileaflet MVP and nonsevere MR (Barlow disease) experienced malignant polymorphic VT and 9 appropriate ICD shocks despite optimal medical management. Serial imaging over several years demonstrated persistent MAD, severe LA dilation, and progressive arrhythmic burden. Importantly, her CMR showed no LGE, reinforcing the concept that electrical instability can precede structural remodeling. Strain imaging revealed supranormal posterolateral strain and mechanical dispersion. We rediscussed the possibility of mitral valve repair to reduce leaflet-chorda–papillary muscle tractions and to eliminate MAD in order to silence the arrhythmic triggers. Ablation remained a backup option. A second opinion at Mayo Clinic endorsed surgical repair despite nonsevere MR. The patient agreed after 2 additional ICD shocks for VT in February 2018. The physical examination before the mitral valve repair procedure was significant for accentuated intensity of S₁, loud midsystolic click, and grade III/VI mid to late systolic apical murmur radiating toward the axilla (Figure 4). The preoperative coronary angiogram was normal.

Figure 4.

Two-Dimensional/Doppler Echocardiography Before Mitral Valve Repair (March 2018)

(A and B) Parasternal long-axis views demonstrating similar findings as the previous echo with markedly dilated LA. (C) Parasternal short axis showing myxomatous leaflet (arrows) note ICD wire in the RV. (D) Apical 4-Chamber view showing dilated LV and LA. (E) Apical 4-chamber view with color Doppler demonstrating the moderate eccentric mid-late MR jet. (F) Pulsed wave (PW) Doppler of posterolateral annulus demonstrating huge pickelhaube spike (44 cm/s). (G) PW Doppler of mitral inflow (E = 0.8, A = 0.6, E/A = 1.3). (H) PW Doppler of the septal mitral annulus (e’ = 7). (I) Pre-op strain study demonstrated despite GLS = 24%, regional strain was markedly increased (supranormal) localized to the posterolateral left ventricular wall at basal and mid-level (trident pattern) indicating high workload (average segmental strain = 29%). ICD = implantable cardioverter-defibrillator; LA = left atrium; LV = left ventricle; RV = right ventricle.

In September 2018, the patient underwent mitral valve repair involving triangular resection of the middle scallop, posterior leaflet (P2), posterior annuloplasty ring placement, LA reduction, LA appendage ligation, and cryoablation of the papillary muscles. This procedure resulted in durable suppression of ventricular arrhythmias and no ICD shocks over a 7-year follow-up.

Question 9: How should postoperative LVOT gradient be interpreted?

Cardiac auscultation after the mitral valve repair demonstrated normal S₁, S₂, grade I-II/VI systolic ejection murmur loudest along the left sternal border, which increased to III/VI in post-PVC beat. Transthoracic echocardiography showed mild residual MR and LVOT gradient (20 mm Hg at rest, 84 mm Hg post-PVC) with systolic anterior motion and normal ejection fraction (60%). Hydration and salt intake, as well as beta-blocker titration, were recommended to mitigate dynamic LVOT obstruction.

The transient postoperative LVOT gradient was consistent, with dynamic obstruction related to systolic anterior motion of the elongated anterior mitral leaflet, reduced ventricular cavity size after annuloplasty and atrial reduction, and hyperdynamic postectopic ventricular contraction. This has been reported in some cases of myxomatous mitral valve repair.¹⁰ The LVOT dynamic obstruction improved with hydration, salt intake, and beta-blockade. Importantly, the gradient completely resolved on follow-ups.

At subsequent follow-ups (Figure 5), cardiac examination showed normal S₁ and S₂, no clicks or murmurs, and a post-PVC grade I-II/VI systolic ejection murmur, best heard on the sternal border. Resting LVOT gradient normalized, with only mild provocable gradients post-PVC. During the 7 years of postoperative follow-ups, the patient has remained asymptomatic and free of ICD shocks (Table 1).

Figure 5.

Two-Dimensional/Doppler Echocardiography After Mitral Valve Repair (October 2023)

(A and B) Parasternal long-axis views after mitral valve repair appearance and no annular disjunction with reduction of the left atrial size. (C) Parasternal short-axis view after mitral valve repair with annuloplasty. (D) Apical 4-chamber view with reduced left ventricular and left atrial size (LAVI: 39 mL/m²) and no annular disjunction. (E) Apical 4-chamber view with color Doppler showing trivial mitral regurgitation. (F) Continuous wave Doppler demonstrating trivial mitral regurgitation. (G) Pulsed-wave Doppler mitral inflow (E = 1, A = 0.8, E/A = 1.3). (H) Pulsed-wave Doppler of septal mitral annulus (e′ = 7 cm/s). (I) Postoperative longitudinal strain bull's eye pattern showing near-normal global longitudinal strain. LAVI = left atrial volume index; other abbreviations as in Figure 2.

Table 1.

Echocardiographic Parameters During Initial Evaluation and Follow-Ups

Date	LVEF (%)	IVS Diastolic Thickness (cm)	LVEDD (cm)	LAVI (mL/m2)	MR Severity	MV Regurgitation Volume (mL)	MV Mean Gradient (mm Hg)	MR Peak Velocity (m/s)	MV Annulus VTI (cm)	PASP(mm Hg)
February 6, 2012	60	1.08	—	53	Mild	28	—	5.3	8.6	—
December 14, 2015	61	0.8	5.6	52	Moderate	29	—	4.7	—	27
August 28, 2018	65	1	5.7	84	Moderate	46	—	5.3	—	30
September 25, 2018	60	1.1	4.7	32	Trivial	—	1.6	—	—	31
October 30, 2023	58	1.3	5.0	39	Trivial	—	2	—	—	37

IVS = interventricular septum; LAVI = left atrial volume index; LVEDD = left ventricular end-diastolic diameter; LVEF = left ventricular ejection fraction; MR = mitral regurgitation; MV = mitral valve; PASP = pulmonary artery systolic pressure; VTI = velocity time integral.

Conclusions

Although malignant MVP is well recognized, this case provides longitudinal, imaging-guided evidence that mechanical arrhythmogenic substrates (MAD, hyperdynamic posterolateral wall segments with high-strain values, large pickelhaube spike) may precede development of severe MR or myocardial fibrosis, and surgical correction can result in durable arrhythmia suppression in carefully selected cases.

Funding Support and Author Disclosures

Dr Niloufar Javadi is supported by a grant from the Crivello Family Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.