Discussion

Arrhythmogenic mitral valve prolapse is a recently identified subgroup of mitral valve prolapse with a more severe clinical course. ^{Reference Kubala, Essayagh and Michelena1–Reference Chakrabarti, Bogun and Liang4,Reference Korovesis, Koutrolou-Sotiropoulou and Katritsis7,Reference Zienciuk-Krajka, Daniçowicz-Szymanowicz and Dorniak8} It is characterised by specific findings, including central annular dysjunction, bileaflet prolapse of the mitral valve, QT prolongation on electrocardiogram, and ventricular ectopic beats, particularly originating from the left ventricle. ^{Reference Sabbag, Essayagh and Barrera3,Reference Chakrabarti, Bogun and Liang4} It is worth noting that the response to established therapies for mitral valve prolapse and related conditions is not consistent in patients with arrhythmogenic mitral valve prolapse syndromev. ^{Reference Thamman9,Reference Coutsoumbas and Pasquale10}

From this case, several important findings were learned:

1. 1. This case represents the first reported paediatric case of arrhythmogenic mitral valve prolapse in our country, indicating the importance of recognising and studying this condition in the paediatric population.

2. 2. The presence of QT prolongation and T-wave inversion in inferolateral leads, which have been previously reported in association with arrhythmogenic mitral valve prolapse syndrome, was observed intermittently in this case. This highlights the variability and intermittent nature of these electrocardiographic findings in patients with arrhythmogenic mitral valve prolapse syndrome.

3. 3. The intermittent nature of QT prolongation in these cases can complicate the selection of appropriate treatments and optimal dose adjustments. It suggests the need for close monitoring and individualised management strategies to address the intermittent QT prolongation and its impact on treatment decisions.

Mitral valve prolapse is the most common valvular anomaly observed in the Western population, and the role of mitral valve prolapse in sudden cardiac arrest remains controversial. ^{Reference Coutsoumbas and Pasquale10,Reference Cipriani and Bauce11,Reference Marano, Lim and Sanchez12} Since 2017, when Giudicessi et al. described “arrhythmogenic mitral valve prolapse”, there has been a growing literature on the concept of arrhythmogenic mitral valve prolapse syndrome. ^{Reference Miller, Dukkipati and Turagam2–Reference Chakrabarti, Bogun and Liang4,Reference Nagata, Bertrand and Levine6,Reference Korovesis, Koutrolou-Sotiropoulou and Katritsis7,Reference Basso, Iliceto, Thiene and Marra13}

From an anatomical point of view, mitral regurgitation was initially recognised as an important component of the process because it disrupts the geometry and orientation of the left ventricle, leading to ventricular enlargement and sudden death. However, the coexistence of features such as T-wave inversion and ventricular arrhythmias in some patients with arrhythmogenic mitral valve prolapse without prominent mitral regurgitation later demonstrated that advanced mitral regurgitation is not an essential component of arrhythmogenic mitral valve prolapse. ^{Reference Cipriani and Bauce11} In addition, fibrosis, particularly in the posterior papillary muscles and postero-basal region, previously attributed to continuous mitral regurgitation flux hitting the free wall during systole, was found to be an mitral regurgitation-independent process. ^{Reference Miller, Dukkipati and Turagam2,Reference Cipriani and Bauce11} Another anatomical component that may be associated with arrhythmogenic mitral valve prolapse is mitral annular dysfunction. Mitral annular dysfunction refers to a degree of separation between the posterior mitral leaflet and the free wall. The degree of mitral annular separation can be measured quantitatively using MRI or even transthoracic ejection. ^{Reference Kubala, Essayagh and Michelena1–Reference Chakrabarti, Bogun and Liang4,Reference Korovesis, Koutrolou-Sotiropoulou and Katritsis7,Reference Thamman9}

Patients with arrhythmogenic mitral valve prolapse syndrome are believed to have areas of scar tissue intermixed with viable myocytes in the adjacent free wall of the left ventricle, papillary muscles, and infero-basal wall, independent of prolapse. ^{Reference Chakrabarti, Bogun and Liang4} These areas of scar tissue have been demonstrated in histopathologic studies and through late gadolinium enhancement studies during MRI.

Borderline QT prolongation due to variable and prolonged repolarisation is not uncommon in patients with mitral valve prolapse. ^{Reference Giudicessi, Rohatgi and Bos5,Reference Giudicessi, Rohatgi and Bos14} However, it is still unknown whether patients with QT prolongation have a worse prognosis compared to those without. It should be noted that QT prolongation can also be observed in patients with arrhythmogenic mitral valve prolapse syndrome. ^{Reference Giudicessi, Rohatgi and Bos5,Reference Giudicessi, Rohatgi and Bos14} Interestingly, some case series in the literature have reported genetic mutations associated with long QT syndrome in patients diagnosed with arrhythmogenic mitral valve prolapse syndrome. However, these patients do not follow the expected course of classic Long QT syndrome and often show unusual responses to standard long QT syndrome treatments. As a result, these cases have been referred to as “atypical Long QT Syndrome” cases. ^{Reference Giudicessi, Rohatgi and Bos5,Reference Giudicessi, Rohatgi and Bos14} On the other hand, approximately 2% of individuals with genetic positive long QT syndrome have coexisting mitral valve prolapse. ^{Reference Giudicessi, Rohatgi and Bos5} While mitral valve prolapse alone is not considered a significant contributor to the long QT clinical phenotype, the combination of arrhythmogenic mitral valve prolapse syndrome and genetic positive long QT syndrome is a complex and potentially lethal association that poses challenges in terms of treatment. ^{Reference Giudicessi, Rohatgi and Bos5} Some authors highlight arrhythmogenic mitral valve prolapse syndrome as the coexistence of three independent risk factors for sudden death: mitral valve prolapse, long QT syndrome, and papillary muscle ventricular tachycardia. ^{Reference Kubala, Essayagh and Michelena1,Reference Chakrabarti, Bogun and Liang4,Reference Nagata, Bertrand and Levine6,Reference Thamman9} In a study by Ackerman et al., it was observed that patients with genetically positive long QT syndrome associated with arrhythmogenic mitral valve prolapse syndrome had more premature ventricular contractions with RBBB morphology during Holter monitoring, longer mean QTc intervals, a higher incidence of life-threatening events, and more positive shocks in implantable cardiac defibrillator recordings after sympathectomy compared to patients without arrhythmogenic mitral valve prolapse syndrome. ^{Reference Giudicessi, Rohatgi and Bos5,Reference Giudicessi, Rohatgi and Bos14} The patient also has mutations in the KCNH2 and ANK2 genes whose clinical significance is unclear. The identified mutation in KCNH2, listed as VUS (variant of uncertain clinical significance) in the Franklin database, has the potential to cause abnormal splicing and cutting effects and is thought to be associated with the current clinical presentation.

T wave inversion in the inferolateral leads, reflecting changes in the direction and duration of repolarisation, is a more common finding than QT prolongation in arrhythmogenic mitral valve prolapse syndrome cases (2,3,10,13). In our case, we observed simultaneous QT prolongation and T wave negativity in the inferolateral leads, and interestingly, QT values returned to normal when the T wave became positive in those leads. We speculate that this may be due to myocytes utilising two different pathways for repolarisation. However, it remains uncertain whether this phenomenon increases the propensity for substrate instability or Torsades de Pointes. Nevertheless, the intermittent and dynamic changes in electrocardiogram findings highlight both electrical and anatomical alterations in arrhythmogenic mitral valve prolapse syndrome cases. These unique features, which fall within the spectrum of arrhythmogenic mitral valve prolapse syndrome but vary from case to case, also influence treatment planning. In our approach, we supplemented beta-blocker therapy with mexiletine to shorten the QTc values measured when T waves were negative by approximately 30 milliseconds. However, mexiletine significantly shortened the QTc values measured when T waves were positive, necessitating a reduction in dosage to avoid exceeding the therapeutic limit. This particular aspect of our case further adds to its complexity and underscores the need for individualised management.

In this patient, the abnormal mitral apparatus creates chronic mechanical traction, particularly on the posteromedial papillary muscle, which has a single blood supply, making it vulnerable to ischaemia and fibrotic remodelling. Mitral annular disjunction creates abnormal systolic twisting motion, generating repetitive mechanical triggers on the basal inferolateral wall. In mitral valve prolapse patients, accompanying autonomic dysregulation-particularly during physical exertion—may lead to excessive stimulation of sympathetic activation. Finally, the alternation of electrocardiogram findings suggests that it likely represents dynamic repolarisation heterogeneity driven by autonomic tone fluctuations on the diseased inferolateral substrate (posteromedial papillary muscle + basal inferior wall).

The role of sympathectomy in the treatment of patients with arrhythmogenic mitral valve prolapse syndrome remains uncertain. ^{Reference Giudicessi, Rohatgi and Bos5,Reference Giudicessi, Rohatgi and Bos14,Reference Kelley, Chaudry and Syed15} While arrhythmogenic mitral valve prolapse syndrome may initially appear as a collection of anatomical defects, individuals with mitral valve prolapse syndrome are known to have increased sympathetic discharge compared to the general population. ^{Reference Giudicessi, Rohatgi and Bos14,Reference Kelley, Chaudry and Syed15} Considering that life-threatening events in these cases result from the interaction between a pathological anatomical substrate and various triggers, sympathectomy may have potential benefits in selected cases (15). In our patient, given the clear adrenergic triggers such as exertion and emotional stress described before the event, we believed that she would benefit from sympathectomy. Although appropriate implantable cardiac defibrillator shocks were reduced following the procedure, they were not completely eliminated. It is worth noting that she experienced an appropriate implantable cardiac defibrillator shock during a period of irregular beta-blocker therapy.

Since the patient in our case had polymorphic premature ventricular contractions originating from multiple sites (posterior papillary muscle, posterior fascicle, and outflow), none of them being dominant and suitable for mapping, ablation was not considered as a primary treatment option. Instead, we focused on transvenous implantable cardiac defibrillator placement and sympathectomy procedures due to the complexity of the premature ventricular contraction patterns and the patient’s clinical presentation.

In conclusion, mitral valve prolapse is a common clinical finding in paediatric patients. However, it is crucial to identify which mitral valve prolapse patients are at a higher risk of sudden death. Recent advancements in data have allowed for the emergence and development of differential electrocardiographic and echocardiographic features that can help identify individuals at higher risk. Comprehensive assessments and algorithms that consider the patient’s personal and family history play a crucial role in accurately diagnosing and differentiating patients with arrhythmogenic mitral valve prolapse, thus avoiding both underdiagnosis and overdiagnosis.