Mitral Annular Disjunction (MAD) And Refractory Ventricular Fibrillation

MitralAnnular Disjunction (MAD) And Refractory Ventricular Fibrillation

A45-year-old male was followed in an outpatient clinic with a moderate mitral valveregurgitation (prolapse of both cusps) and mitral annular disjunction (MAD).

Transthoracicechocardiography documented:

·        Normal ejection fraction of leftventricle

·        Moderate mitral valve regurgitation(grade 3/4)

·        An 8-mm mitral annular disjunction(considered the most likely underlying substrate for the ventricularfibrillation)

Repeatedly,the patient had been informed of the need to undergo a cardiac MRI and to avoidstrength training and strenuous physical activity; however, he did not adhereto these recommendations. In June 2026, he was admitted following a witnessed out-of-hospitalcardiac arrest (OHCA) after excessive sport activity. Bystander cardiopulmonaryresuscitation (CPR) was initiated immediately after collapse. The initialrhythm was ventricular fibrillation (VF). An automated external defibrillator(AED) advised defibrillation, and two shocks were delivered before the arrivalof the prehospital advanced life support (ALS) team. Following ALS arrival,rhythm analysis was performed every 2 minutes and demonstrated persistent VF.Amiodarone (300 mg IV) was administered after the third defibrillation,followed by an additional 150 mg after the fifth shock. Adrenaline wasadministered according to current ALS guidelines. Patient exhibited agonalgasping and underwent rapid-sequence induction with succinylcholine, followedby endotracheal intubation. Mechanical chest compressions were continued usingthe LUCAS chest compression system. Despite a total of eight biphasic 200-Jdefibrillation shocks, VF remained refractory.

ECG stripefrom the Emergency car documenting refractory VF.

Giventhe refractory VF, the patient was referred for extracorporeal cardiopulmonaryresuscitation (ECPR), and the extracorporeal membrane oxygenation (ECMO) teamwas activated. Veno-arterial ECMO was established 55 minutes after collapse, withreturn of spontaneous circulation (ROSC) achieved 58 minutes after the onset ofcardiac arrest.

Initialassesment

Afteradmission, a comprehensive post-resuscitation intensive care was initiated.Toxicology screening was negative. Following initial volume resuscitation, thepatient developed pulmonary oedema, which responded well to diuretic therapy.

Transthoracicechocardiography on admission documented:

·        left ventricular ejection fraction(LVEF) of 45% with diffuse hypokinesia

·        hypertrophic LV, patent foramenovale (PFO) with a left-to-right interatrial shunt

·        severe mitral regurgitation (grade3/4)

·        an 8-mm mitral annular disjunction(considered the most likely underlying substrate for the ventricularfibrillation)

·        mild aortic regurgitation (grade1/4)

CLINICAL COURSE

In hospital summary:

Onthird day, uncomplicated VA-ECMO decannulation was performed, with closure ofthe femoral arterial access site using a MANTA vascular closure device. Thepatient remained haemodynamically stable thereafter but exhibited a tendencytowards central hypertension requiring treatment with urapidil.

Dueto persistently elevated inflammatory markers, empirical antibiotic therapy wasinitiated despite the absence of microbiologically confirmed infection.Following withdrawal of sedation, the patient failed to regain consciousness.Serial brain CT examinations demonstrated progressive cerebral oedema, globallyreduced differentiation between grey and white matter, and narrowing of theventricular system. Neurological assessment was consistent with diffuse hypoxiccortico-subcortical encephalopathy. Clinically, the patient remained in a vigilcoma with decerebrate posturing and generalized hypoxic myoclonic movements.Brainstem reflexes remained intact; however, the overall neurological prognosiswas considered unfavourable.

Afurther complication was the development of acute kidney injury (AKI). Despitepreserved urine output and the absence of hyperkalaemia, intermittenthaemodialysis (IHD) was initiated on the fifth day of hospitalization becauseof uraemia. A total of three IHD sessions were performed.

Laboratoryfindings revealed progressive anaemia, considered multifactorial in origin(haemodilution, consumption related to mechanical circulatory support, andfrequent blood sampling). On the sixth day, the patient received two units ofpacked red blood cells. On the eighth day, percutaneous dilatational tracheostomywas performed without complications.

Thepatient's clinical condition and poor neurological prognosis were discussedrepeatedly and comprehensively with the family. Given the unfavourableprognosis and overall clinical situation, the patient was transferred to apalliative care unit for further management.

DISCUSSION:

Arrhythmogenic mitral valve prolapse(AMVP) is a clinical phenotype of mitral valve prolapse (MVP), which affectsapproximately 2–3% of the population and is usually considered a benigncondition. MVP is the most frequent cause of primary or degenerative mitralregurgitation (MR). A subset of patients develops an arrhythmogenicphenotype associated characterized by an increased risk of malignantventricular arrhythmias (VAs), sudden cardiac arrest (SCA), and sudden cardiacdeath (SCD).

Mitral annular disjunction (MAD) isa structural abnormality defined by a separation between the mitral valveannulus and the basal left ventricular myocardium, resulting in excessiveannular mobility during systole. Increasing longitudinal extent of MAD isassociated with greater systolic annular "curling" and inferolateralventricular outpouching, leading to repetitive mechanical stretch of thepapillary muscles and adjacent myocardium. Chronic mechanical stress isthought to activate profibrotic signalling pathways, ultimately resulting in replacementfibrosis that serves as an arrhythmogenic substrate. Thismechano-electrical interaction is considered one of the principal mechanismslinking MAD to ventricular arrhythmogenesis.

The clinical spectrum of MAD rangesfrom asymptomatic incidental findings to life-threatening ventriculararrhythmias, SCA and SCD. Patients presenting with unexplained syncope orpresyncope require careful evaluation for occult ventricular arrhythmias.

Additional high-risk markers includebileaflet myxomatous prolapse, redundant mitral leaflets, the presence of MAD,inferolateral T-wave inversion on resting electrocardiography, and myocardialfibrosis demonstrated by late gadolinium enhancement (LGE) on cardiac magneticresonance. Sustained ventricular tachycardia, spontaneous polymorphicventricular tachycardia, or rapid non-sustained monomorphic ventriculartachycardia (>180 bpm) are regarded as high-risk arrhythmic featuresassociated with an increased risk of SCD.

Diagnosis

Transthoracic echocardiography (TTE)is the first-line imaging modality for evaluating mitral valve disease andidentifying MVP. A separation of ≥5 mm between the posterior mitral leafletinsertion and the basal left ventricular myocardium is generally considereddiagnostic. The Pickelhaube sign—a sharp systolic velocity spike (>16cm/s) of the lateral mitral annulus on tissue doppler imaging—has emerged as amarker of excessive annular motion and increased arrhythmic susceptibility.

MuthukumarL, et al. The Pickelhaube Sign: Novel Echocardiographic Risk Marker for MalignantMitral Valve Prolapse Syndrome. JACC Cardiovasc Imaging. 2017Sep;10(9):1078-1080. doi: 10.1016/j.jcmg.2016.09.016.

Electrocardiography may revealinferolateral T-wave inversion, QTc prolongation, or frequent prematureventricular complexes. Ambulatory ECG Holter monitoring is recommended toquantify ventricular ectopy and detect non-sustained ventricular tachycardia,while exercise testing may identify exercise-induced ventricular arrhythmias.

Cardiac magnetic resonance imaginghas become an essential component of risk stratification in AMVP. CMR enablesdetection of myocardial fibrosis within the papillary muscles or basalinferolateral left ventricular wall using late gadolinium enhancement and T1mapping.

Although the genetic basis of AMVPremains incompletely understood, pathogenic variants involving structuralproteins, particularly titin (TTN), have been reported in selected patients.

Management

Management of AMVP should beindividualized and based on arrhythmic burden, myocardial substrate, and mitralvalve morphology rather than on the presence of MAD alone.

Medical therapy is primarilyindicated for symptomatic ventricular ectopy, non-sustained ventriculararrhythmias, suspected premature ventricular complex (PVC)-inducedcardiomyopathy, or left ventricular systolic dysfunction not fully explained bymitral regurgitation. Beta-blockers and non-dihydropyridine calcium-channelblockers remain first-line agents and provide symptomatic relief, althoughtheir effect on reducing PVC burden is generally modest. Class ICantiarrhythmic drugs or amiodarone may be considered in carefullyselected patients, balancing antiarrhythmic efficacy against the potential forlong-term adverse effects.

Catheter ablation may be considered in patients with symptomatic orhigh-burden PVCs refractory to medical therapy, PVC-induced cardiomyopathy, orclearly identifiable triggers arising from the papillary muscles or Purkinjesystem.

Implantable cardioverter-defibrillator(ICD) therapy is recommended for secondary prevention in patients withprevious sudden cardiac arrest, ventricular fibrillation, or sustainedventricular tachycardia in the absence of reversible causes. Current evidencedoes not support routine prophylactic ICD implantation based solely on thepresence of MAD or MVP, and decisions regarding primary prevention shouldtherefore be individualized.

Mitral valve surgery is indicated according to current valvular heart diseaseguidelines in patients with severe degenerative mitral regurgitationaccompanied by symptoms or left ventricular dysfunction. In selected patients,surgical correction may also reduce ventricular arrhythmia burden byeliminating the abnormal mechanical forces acting on the papillary muscles andmitral annulus. This potential antiarrhythmic benefit appears greatest inpatients with pronounced MAD, excessive annular hypermobility, papillary muscletraction, and limited or absent myocardial fibrosis on CMR.

Lifestyle Recommendations

Patients with AMVP and documentedventricular arrhythmias should avoid high-intensity competitive sports andstrenuous resistance exercise, particularly activities such as bodybuilding, asexercise-induced tachycardia and marked increases in blood pressure may augmentmechanical stress on the mitral valve apparatus and potentially increasearrhythmic risk. Participation in recreational physical activity should beindividualized.

References

1.     PiscioneM, Pala B, Cribari F, Vignaroli W, Mroue J, Mehta V, Matar F, Perrone MA. TheArrhythmogenic Spectrum of Mitral Valve Disease: Pathophysiology, RiskStratification, and Surgical Management. J Clin Med. 2026 Jan 21;15(2):865.doi: 10.3390/jcm15020865. PMID: 41598802; PMCID: PMC12841869.

2.     Kotyza,V., Segeťová, M., Skalická, B., Peichl, P., Peldová, P., Macek, M., Jr.,Kautzner, J., & Krebsová, A. (2026). Arytmogenníprolaps mitrální chlopně, retrospektivní hodnocení možností odhadu rizika životohrožujících arytmií. Cor et Vasa, 68(3), 308–313.https://doi.org/10.33678/cor.2025.136

3.     ChianeseS, Ordine L, Pacella D, Canciello G, Di Napoli S, Lombardi R, Esposito G, LosiMA. Arrhythmic risk in mitral valve prolapse with mitral annular disjunction:meta-analysis of longitudinal studies. Sci Rep. 2025 Dec 16;16(1):2428. doi: 10.1038/s41598-025-32285-3.PMID: 41402368; PMCID: PMC12820290.

4.     CraigHacking, Mitral annular disjunction, Radiopaedia.org,Available from: https://radiopaedia.org/articles/mitral-annular-disjunction-1

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