Available via license: CC BY 4.0
Content may be subject to copyright.
Received: May 9, 2023. Accepted: May 25, 2023
Published by Oxford University Press and JSCR Publishing Ltd.© The Author(s) 2023.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which
permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Journal of Surgical Case Reports, 2023, 6,1–3
https://doi.org/10.1093/jscr/rjad344
Case Series
Case Series
Twin hearts—minimally invasive mitral valve repair
in twin sisters with mitral annular disjunction
and Loeys-Dietz syndrome: a case series
Stelios Ioannou1, *, George Shiakos1,Theodoros Ntoskas2,Elias Papasavvas3,Violetta Anastasiadi4, Nikoleta Betsimea Loizides5,
Petros Mavrommatis 6and Ioannis Tzanavaros1
1Cardiac Innovation Center of Apollonion Private Hospital, Nicosia, Cyprus
2Mediterranean Hospital of Cyprus, Limassol, Cyprus
3Apollonion Private Hospital, Nicosia, Cyprus
4Karaiskakio Foundation, Nicosia, Cyprus
5Saint Andrews Cardiological Centre Paphos, Paphos, Cyprus
6Cardiac Care Centre, Paphos, Cyprus
*Correspondence address. Cardiac Innovation Center of Apollonion Private Hospital, Lefkotheou Avenue 20, 2054 Strovolos, Nicosia, Cyprus.
Tel : +35722469071; Fax: +35722206934; E-mail: stelios.ioannou@apollonion.com.cy
Abstract
In this case report, we present 31-year-old twin sisters diagnosed with severe Barlow mitral valve prolapse, mitral annular disjunction
and presence of lateral mid-wall fibrosis diagnosed on MRI as well as ventricular arrhythmias, and a very rare variant of Loeys-Dietz
syndrome, being referred to our center for surgical repair.Genetic testing detected pathogenic variants of clinical significance in SMAD3
and KCNH2 genes that are associated with autosomal dominant disease of Loeys-Dietz syndrome. Due to the presence of severe mitral
valve regurgitation, the first patient was referred for minimally invasive mitral valve repair that was performed successfully. Before
discharge, a subcutaneous ICD implantation was performed as primary prevention against malignant ventricular arrhythmias and
sudden cardiac death. Her twin sister presented with the identical diagnosis and underwent the same surgical procedure with S-ICD
implantation a few months later.
INTRODUCTION
We share a case report of twin sisters genetically diagnosed with
a rare variant of Loeys-Dietz syndrome, presenting also with a
severe Barlow mitral valve prolapse and mitral annular disjunc-
tion (MAD). Sudden cardiac death of a younger sister at the age of
thirteen is reported in the family history.
Mitral annular disjunction is a structural abnormality of the
mitral annulus fibrosus, which has been described by patholo-
gists to be associated with mitral leaflet prolapse. Mitral annular
disjunction is a common finding in patients with myxomatous
mitral valve diseases. The prevalence of mitral annular disjunc-
tion should be checked routinely during presurgical imaging.Oth-
erwise, mitral annular disjunction itself might be an arrhythmo-
genic entity, irrespective of the presence of mitral valve prolapse
(MVP) that can lead to sudden cardiac death [1].
Its recognition in transthoracic and confirmation on trans-
esophageal echocardiography is important to facilitate optimal
mitral valve repair. The modification of the repair technique
allows surgical correction of the annular disjunction, which
seems to optimize long-term results in these challenging cases [2].
The importance of genetically diagnosed variations of Loeys-Dietz
syndrome should be highlighted, as in rare cases,the combination
of mitral annular disjunction can be of clinical significance or
even fatal if not treated.
Mutations in the SMAD3 gene have been found to cause Loeys-
Dietz syndrome type III. The SMAD3 gene provides instructions
for making the protein necessary for the signaling pathway of
the transforming growth factor-beta (TGF-β). Through the TGF-
βsignaling pathway, the SMAD3 protein also influences many
aspects of cellular processes, including cell growth and divi-
sion (proliferation), cell movement (migration) and controlled cell
death (apoptosis) [3]. The overactive signaling pathway leads to
dysregulated cell proliferation and gene activation. These changes
lead to the abnormalities typical of Loeys-Dietz syndrome type III.
On the other hand, the KCNH2 gene belongs to a family of genes
that provide instructions for making potassium channels. Those
channels are found in the cardiac muscles and are responsible
for the generation and transmission of electrical signals. Health
conditions related to genetic changes of this gene are Romano-
Ward syndrome, Short-QT syndrome, Familial atrial fibrillation
and can be even associated with acquired long QT syndrome and
increased risk for sudden cardiac death [4].
Downloaded from https://academic.oup.com/jscr/article/2023/6/rjad344/7199933 by guest on 19 June 2023
2|S. Ioannou et al.
Figure 1. Preoperative echocardiography of patient 1.
Figure 2. Preoperative echocardiography of patient 2.
Figure 3. Midwall fibrosis in the mid-anterolateral wall of patient 1.
CASE SERIES
In this case report, we present 31-year-old twin sisters diagnosed
with severe Barlow mitral valve prolapse and mitral annular
disjunction and presence of lateral mid-wall fibrosis diagnosed
on MRI as well as ventricular arrhythmias,and a very rare variant
of Loeys-Dietz syndrome type III, being referred to our center
for surgical repair. The sudden death of their otherwise healthy
thirteen-year-old sister a few years ago due to unknown causes
prompted further cardiological evaluation.
Clinically, both patients complained of worsening palpitations
over the last few months with no associated dyspnea or tiredness.
A Holter examination recorded 14 444 VES and 212 NSVT, with
very similar results in both sisters. The echocardiography revealed
a myxomatous Barlow mitral valve with anterior and posterior
leaflet prolapse and two regurgitant jets resulting in moderate
to severe mitral valve regurgitation as well as mitral annular
disjunction in both cases (Figs 1 and 2). A cardiac MRI on a
3 T Lumina Siemens revealed at the mid-left ventricular level, a
midwall fibrosis in the midlateral myocardium (Figs 3 and 4)and
confirmed a mitral annular disjunction of 12 mm (Figs 5 and 6).
Additional findings included a dilated LV with mildly depressed
contractility, no visible myocardial scarring, no structural heart
disease and a normal sized RV with mildly depressed contractility.
Taking into consideration the presence of moderate to severe
mitral valve regurgitation and the arrhythmogenic potential
of the diagnosed mitral annular disjunction especially with a
reported case of sudden cardiac death in the family history,
surgical repair in both sisters was planned. Both patients were
instructed to avoid strenuous physical activities, and both were
placed on low-dose beta-blocker therapy preoperatively.
Figure 4. Midwall fibrosis in the mid-anterolateral wall of patient 2.
Figure 5. Mitral annular disjunction 12 mm of patient 1.
Figure 6. Mitral annular disjunction 12 mm of patient 2.
Both sisters underwent a minimally invasive procedure
through a right-sided lateral minithoracotomy performed at the
level of the third or fourth intercostal spaces. Cardiopulmonary
bypass was established through a femoral access and cardioplegic
cardiac arrest was achieved through a modified Del Nido
solution (20 ml/kg). Mitral valve repair was performed through
isolated annuloplasty using in both cases a 38-mm semi-rigid
annuloplasty ring. Transesophageal echocardiography after repair
revealed excellent surgical results, with no rest regurgitation,
no SAM of the mitral valve and most importantly no detectable
mitral annular disjunction (Figs 7 and 8). In both cases, being
performed several months apart, the patients were extubated
in the operating room and transferred to our ICU for further
observation.
The postoperative course was largely uneventful and both
sisters made an excellent recovery. Both were kept on monitoring
throughout the in-hospital stay and no relevant ventricular or
supraventricular arrhythmias were documented under the estab-
lished beta-blocker therapy. After individual risk stratification
and taking in to account the reported case of sudden cardiac
Downloaded from https://academic.oup.com/jscr/article/2023/6/rjad344/7199933 by guest on 19 June 2023
Minimally invasive mitral valve repair in twin sisters |3
Figure 7. Postoperative echocardiography of patient 1.
Figure 8. Postoperative echocardiography of patient 2.
death within the family, and the recorded episodes of NSVT
preoperatively, we proceeded with an S-ICD implantation in both
cases before discharge from the hospital. Follow up at 7 and
30 days after discharge confirm excellent operative results and
both patients remain asymptomatic. Analysis of the S-ICD data
in a postoperative check, revealed no episodes of ventricular
tachycardia in none of the patients.
DISCUSSION
Rare cases like this lead us to consider the importance of genetic
examinations of patients as well as their families with heart
diseases and elastopathies. On the other hand, mitral annular
disjunction itself can be an arrhythmogenic entity that can lead
to sudden cardiac death. This rare condition is seen in about 30%
of the patients with mitral valve prolapse based upon different
populations and imaging modalities [5]. As its diagnosis may have
further implications in the planning of the surgical therapy as well
as postoperative rhythmological considerations, mitral annular
disjunction must be considered in all patients with mitral valve
prolapse especially in the setting of Barlow’s disease.
In our reported case, both patients underwent an S-ICD
implantation before discharge as they were both considered
to have a high risk of sudden cardiac death. The role of ICD
implantation as primary prevention in such cases is unclear as
available data are limited. We consider an individual risk stratifi-
cation of such patients appropriate taking into consideration the
arrhythmogenic potential of MAD, myocardial fibrosis, medical
history of malignant arrhythmias and family history. In our case,
both sisters presented with a large longitudinal distance of MAD
in magnetic resonance, severe Barlow’s disease at a young age,
and a reported case of sudden cardiac death in the family all of
which are predictors of arrhythmias in MAD [6]. The choice of
subcutaneous ICD implantation vs. transvenous was made solely
on the patient’s age and preservation of their quality of life.
To conclude, in this report, we present a case of successful
mitral valve repair in twin sisters with severe Barlow mitral
valve prolapse, mitral annular disjunction and a very rare vari-
ant of Loeys-Dietz syndrome. Although, the hereditary nature of
Barlow’s disease is well documented, this is to our knowledge
the first reported case of twins with severe Barlow mitral valve
prolapse, MAD and lateral mid-wall myocardial fibrosis being
treated successfully in an identical manner. The significance of
the diagnosis of MAD should be emphasized especially in younger
patients with MVP and further research is required as to the role of
ICD implantation as primary prevention for sudden cardiac death
in such patients.
CONFLICT OF INTEREST STATEMENT
None declared.
FUNDING
None.
REFERENCES
1. Tani T, Konda T, Kitai T, Ota M, Furukawa Y. Mitral annular
disjunction-a new disease Spectrum. Cardiol Clin 2021;39:289–94.
2. Eriksson MJ, Bitkover CY, Omran AS, David TE, Ivanov
J, Ali MJ, et al. Mitral annular disjunction in advanced
myxomatous mitral valve disease: echocardiographic detection
and surgical correction. J Am Soc Echocardiogr 2005;18:
1014–22.
3. LiuL,LiuX,RenX,TianY,ChenZ,XuX,et al. Smad2 and
Smad3 have differential sensitivity in relaying TGFβsignal-
ing and inversely regulate early lineage specification. Sci Rep
2016;6:21602.
4. Alders M, Bikker H, Christiaans I. Long QT Syndrome. 2003 Feb 20
[updated 2018 Feb 8]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace
SE, B LJH, Gripp KW, Amemiya A, editors. GeneReviews®
[Internet]. Seattle (WA): University of Washington, Seattle;
1993–2023.
5. Wu S, Siegel RJ. Mitral annular disjunction: a case series and
review of the literature. Front Cardiovasc Med 2022;9:976066.
6. Dejgaard LA, Skjølsvik ET, Lie ØH, Ribe M, Stokke MK, Hegbom F,
et al. The mitral annulus disjunction arrhythmic syndrome. JAm
Coll Cardiol 2018;72:1600–9.
Downloaded from https://academic.oup.com/jscr/article/2023/6/rjad344/7199933 by guest on 19 June 2023
