Arrhythmic mitral valve prolapse and its association with sudden cardiac death
DIEGO X. CHANGO AZANZA 1,2, MARTÍN A. MUNÍN 1, VÍCTOR TORRES 1
1. Ultrasonido Cardiovascular (CEMIC) “Norberto Quirno”. BA, Argentina. 2. Maestría de Ultrasonido en Cardiología de Facultad de Ciencias Médicas de la Universidad Nacional de la Plata (UNLP). Buenos Aires, Argentina.
Recibido 06-MAYO-2019 – ACEPTADO después de revisión el 21-JUNIO-2019.
There are no conflicts of interest to disclose.
Mitral valve prolapse (MVP) affects 2% to 3% of the general population; its main sequelae include mitral valve regurgitation, heart failure, infectious endocarditis and a possible and disturbing association with sudden cardiac death (SCD). We present the case report of a 30-year-old asymptomatic woman in her usual life, with evidence of Nonsustained Ventricular Tachycardia (NSVT) on multiple occasions. Transthoracic echocardiography revealed degenerative disease due to mitral valve prolapse with moderate to severe valvular regurgitation and Mitral Annulus Disjunction with hypermobility of the posterolateral wall of the left ventricle (LV). Magnetic Resonance Imaging (MRI) showed increased volumes, mild deterioration of ejection fraction and absence of focal fibrosis of the LV. Multiple clinical and cardiac imaging factors have been described that would allow identifying those patients with increased risk for the development of SCD.
Mitral valve prolapse (MVP) is estimated to affect 2 to 3% of the general population. It is defined as a shift of 2 mm or more during systole and myxomatous degeneration of the mitral valve, with thickening greater than 5 mm during diastasis .
The real annual rate of sudden cardiac death (SCD) in a context of MVP remains unknown. Although some observational studies have described a yearly prevalence of 0.9 to 1.9%, there is significant heterogeneity in the methods used for diagnosis and populations in study . However, it is necessary to emphasize the risk factors that would allow to predict the development of fatal ventricular arrhythmias in this group of patients.
Female, 30-year-old patient, referred due to frequent premature ventricular contractions in routine control, asymptomatic in her usual life and did not present personal or family history of SCD. Physical examination revealed systolic murmur in 4/6 mitral focus radiated to armpit, with no other relevant findings. In the electrocardiogram, no alterations were observed in ventricular depolarization or repolarization, with QT interval within normal limits. Further, she presented bigeminal premature ventricular contractions with probable origin in the anterior papillary muscle. ECG monitoring of 24 h showed episodes of nonsustained VT several times (the longest one of 8 beats) with no associated symptoms (Figure 1).
Figure 1. (A) Twelve-lead ECG: sinus rhythm with bigeminal ventricular arrhythmia. The premature ventricular contraction originates in the LV with probable focus on the anterior papillary muscle. (B) ECG monitoring of 24 h: evidence of nonsustained VT of four beats.
Transthoracic echo revealed degenerative disease by mitral valve prolapse with compromise in both leaflets and regurgitation in a moderate to severe degree (Figure 2). MVP this time, was associated to annulus disjunction with LV posterolateral wall hypermobility. Strain analysis showed increase in segmental longitudinal shortening in this region (Figure 3).
Figure 2: Mitral valve prolapse and moderate-to-severe regurgitation. (A) Apical four-chamber view of the LV: myxomatous mitral valve with evidence of bileaflet prolapse. (B) Eccentric mitral valve regurgitation jet that reaches the roof of the left atrium. (C) Mitral flow chart with absence of valve hyperflow. (D) Color M-mode echocardiography shows regurgitant jet that does not hold the whole ventricular systole, confined to mesotelesystole. (E) Continuous mitral transvalvular Doppler.
Figure 3. Mitral annulus disjunction. (A) Left parasternal long axis showing a wide “annular disjunction” separation of 17 mm between the ventricular wall and the base of the posterior mitral annulus. (B) Longitudinal strain with increase in the shortening of LV posteromedial segment of -37%.
LV 3D echo revealed increased volumes with mildly depressed ejection fraction and absence of other significant associated valve alterations (Figure 4).
Figure 4. LV 3-D analysis. A telediastolic volume of 119 ml, telesystolic volume of 58 ml are estimated, and EF estimated in 51.3%.
Cardiac magnetic resonance imaging (CMR) showed mild increase in LV volumes (telediastolic of 110 ml and telesystolic of 57 ml) and ejection fraction estimated in 53%. Moreover, absence of LV and papillary muscles late enhancement was observed (Figure 5).
Figure 5. Cardiac magnetic resonance imaging. (A) LV four-chamber and short axis cine sequences. (B) Late enhancement sequences showing absence of focal fibrosis.
The performance of a stress test by stress echo was well tolerated and showed good functional class (14 Mets), with no symptoms appearing. No segmental alterations in parietal motility or increase in valve regurgitation degree were induced. Frequent monofocal ventricular arrhythmia (bigeminy and couplets) were verified, and no sustained arrhythmias were observed.
Pharmacological treatment with beta blockers (bisoprolol in the maximal tolerated dose) decreased the total number of PVCs, even with nonsustained ventricular arrhythmia in subsequent monitoring visits.
The probable arrhythmic origin of the LV in the presence of MVP could be related, mainly in cases where imaging testing allows to determine an anatomical substrate for its development. Multiple risk factors have been described in an attempt to predict SCD in this exceptional set of patients; however, its direct causal relation is not completely clear.
Some studies have shown that 70% to 90% of patients with ventricular arrhythmia and MVP are women; the reason for this finding is still unknown . A percentage greater than 70% with history of SCD and MVP present T-wave alterations in the electrocardiogram (negative or biphasic T waves in leads DII, DIII and aVF) . However, another study showed that up to 40% of patients with T-wave alterations in ECG with MVP do not present history of evidence of ventricular arrhythmia .
The presence of bileaflet prolapse has been described as a characteristic of high risk and although related to major ventricular arrhythmia, long-term follow-up in these patients did not determine a greater need of implantable cardioverter defibrillator (ICD) or greater incidence of SCD . Although the presence of moderate-to-severe mitral valve regurgitation constitutes an independent predictor for the appearance of ventricular arrhythmia, a high percentage of patients also present negligible-to-mild degree of insufficiency .
A new echocardiographic indicator was described to identify patients in major arrhythmic risk. The presence of hypermobility of the LV posteromedial wall with apical shift, manifest by peak systolic velocity of more than 16 cm/sec in Tissue Doppler in the LV lateral wall, or “Pickelhaube sign” allowed to determine more ventricular arrhythmia load, a greater number of implanted ICDs and presence of late enhancement in CMR . The hypothesis arose that the tension produced by the prolapse on the posteromedial papillary muscle and inferior wall induces subvalvular fibrosis, with this being the anatomical substrate for lethal arrhythmias.
Mitral annulus disjunction has generated an increasing interest in MVP, defined as a disinsertion of the aortic annulus from the ventricular myocardium, or ventricular-arterial detachment at the base of the posterior annulus. Although it has been described as a normal anatomical variant in a minority of patients, a prevalence close to 55% of patients has been verified, when associated to MVP . Three-dimensional transesophageal echo determined a greater number of prolapsing segment and greater volume of prolapse in individuals with the mentioned characteristics .
Its relation to SCD is not clear; however, the presence of disjunction greater than 8.5 mm has properly identified 67% of patients that exhibited nonsustained ventricular tachycardia in ECG monitoring .
CMR allows to define and characterize the composition of the myocardium and the presence of focal fibrosis as arrhythmic substrate in MVP. A high incidence of late enhancement has been observed in patients with ventricular arrhythmia, in the inferobasal segments of the LV in 93% and in the papillary muscles in up to 88% of cases . The presence of interstitial fibrosis detected by T1 mapping technique indicates subclinical global systolic dysfunction and may determine the origin of ventricular arrhythmias; even without focal fibrosis detected by late enhancement with gadolinium . It has been suggested that subclinical diffuse fibrosis constitutes a precursor of focal fibrosis in MVP and could be a marker for early identification in patients in risk of SCD .
Other factors could be intimately related to SCD in MVP. The association of mitral valve prolapse and channelopathies, long QT syndrome, short QT syndrome, concealed preexcitation or anomalous pathways, CAD or myocarditis that may produce malignant ventricular arrhythmias and increase the risk of SCD and other substrates such as early repolarization, have all been described. One or more of these conditions may coexist, favoring the risk of SCD in a minority of cases. From there, it is mandatory to rule out all these possibilities in patients with MVP and malignant ventricular arrhythmias to guide therapeutic customized decision-making .
There are no recommendations in the guidelines with regard to ICD implantation for primary prevention in this group of patients . Some authors suggest the performance of electrophysiology study with protocols of arrhythmia induction in selected cases of patients with evidence of myocardial scar (anatomical substrate) and frequent ventricular ectopy (trigger), in whom the induction of monomorphic VT with 3 extrastimuli and of polymorphic VT or VF with 2 extrastimuli are considered as positive and the implantation of ICD could be recommended. When the study cannot be conducted, the implant of a loop recorder may better select the patients that will benefit from this therapy . Scant catheter ablation reports have shown a rate of success of the procedure close to 89% and a reduction in the number of therapies in patients with ICD .
In the light of the current evidence, the presence of several parameters would allow selecting the patients in greater risk of developing complex ventricular arrhythmia and SCD; nevertheless, there is no clear and determining causal association of valve prolapse in this entity. Studies are required with long-term follow-up in these patients, in whom it is necessary to rule out other associated conditions, along with the use of cardiac imaging studies by echocardiography and CMR with late enhancement and T1 mapping, which would enable the identification in a better manner, of the causal relation between MVP and the controversial associated SCD.
Mitral valve prolapse constitutes a very frequent entity in the general population; its association with sudden cardiac death is still controversial. The presence of multiple risk factors has been described, to stratify patients in high risk of presenting complex ventricular arrhythmia. Female gender, ECG alterations, bileaflet prolapse with significant regurgitation, the presence of focal fibrosis by late enhancement in LV inferobasal walls and papillary muscles, and the presence of diffuse fibrosis detected by T1 mapping in CMR may show the anatomical substrate that may justify the attribution of complex ventricular arrhythmia to MVP.
Delling FN, Rong J, Larson MG, et al. Evolution of mitral valve prolapse: insights from the Framingham Heart Study. Circulation 2016; 133: 1688-95.
Zuppiroli A, Mori F, Favilli S, et al. Arrhythmias in mitral valve prolapse: relation to anterior mitral leaflet thickening, clinical variables, and color Doppler echocardiographic parameters. Am Heart J. 1994; 128 (5): 919-27.
Basso C, Perazzolo Marra M, Rizzo S, et al. Arrhythmic mitral valve prolapse and sudden cardiac death. Circulation 2015; 132: 556-66.
Bhutto ZR, Barron JT, Liebson PR, et al. Electrocardiographic abnormalities in mitral valve prolapse. Am J Cardiol 1992; 70: 265-66.
Nordhues BD, Siontis KC, Scott CG, et al. Bileaflet mitral valve prolapse and risk of ventricular dysrhythmias and death. J Cardiovasc Electrophysiol 2016; 27: 463-68.
Turker Y, Ozaydin M, Acar G, et al. Predictors of ventricular arrhythmias in patients with mitral valve prolapse. Int J Cardiovasc Imaging 2010; 26: 139-45.
Muthukumar L, Rahman F, Jan MF, et al. The Pickelhaube sign: novel echocardiographic risk marker for malignant mitral valve prolapse syndrome. J Am Coll Cardiol Img 2017; 10: 1078-80.
Carmo P, Andrade MJ, Aguiar C, et al. Mitral annular disjunction in myxomatous mitral valve disease: a relevant abnormality recognizable by transthoracic echocardiography. Cardiovasc Ultrasound 2010; 8: 53.
Lee AP, Jin CN, Fan Y, et al. Functional Implication of Mitral Annular Disjunction in Mitral Valve Prolapse: A Quantitative Dynamic 3D Echocardiographic Study. JACC Cardiovasc Imaging 2017; 10 (12): 1424-33.
Sheppard MN, Steriotis AK, Sharma S. Letter by Sheppard et al regarding article, “arrhythmic mitral valve prolapse and sudden cardiac death." Circulation 2016; 133: e458.
Bui AH, Roujol S, Foppa M, et al. Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia. Heart 2017; 103: 204-9.
Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. J Am Coll Cardiol 2018; 72: e91–220. Erratum in: J Am Coll Cardiol 2018; 72: 1760.
Miller MA, Dukkipati SR, Turagam M, et al. Arrhythmic mitral valve prolapse. J Am Coll Cardiol 2018; 72 (23 Pt A): 2904-14.
Syed FF, Ackerman MJ, McLeod CJ, et al. Sites of successful ventricular fibrillation ablation in bileaflet mitral valve prolapse syndrome. Circ Arrhythm Electrophysiol. 2016; 9 (5) doi: 10.1161/CIRCEP.116.004005.