Case Report: Challenges in the etiology of left ventricular aneurysm

Left ventricular aneurysms are outpouchings delineated by a thin myocardial wall, more frequently encountered at the apex of the left ventricle, which is seldom dyskinetic or akinetic. Apart from coronary artery disease, the etiology can be challenging. We report the case of a 30-year-old man with an isolated apical left ventricular aneurysm associated with prominent trabeculations on echocardiography.


Background
Left ventricular aneurysms are outpouchings delineated by a thin myocardial wall, more frequently encountered at the apex of the left ventricle, which is seldom dyskinetic or akinetic 1 .Apart from coronary artery disease, the etiology can be challenging.We report the case of a 30-year-old man with an isolated apical left ventricular (LV) aneurysm associated with prominent trabeculations on echocardiography.

Case report
A 30-year-old male, presented to CHU Brugmann in October 2021 with complaints of dyspnea, chest pain, palpitations, and fatigue persisting since January 2021.The patient was born in Armenia and had arrived in Brussels in 2016.He had a medical history of undocumented arrhythmia and systemic tuberculosis at 18 years of age in Armenia.In January 2020, he presented at another hospital with a spontaneous pneumothorax that required hospitalization.He had been smoking since the age of 17 years.Due to his medical condition, he is currently unemployed.His family history included his father's sudden cardiac death at the age of 55 years.
A coronary angiogram was performed, which revealed normal coronary arteries.A cardiac computed tomography (CT) scan and magnetic resonance (CMR) confirmed that the apical outpouching was indeed a LV aneurysm (Figure 3 and Figure 4).
An implantable loop recorder revealed one episode of nonsustained ventricular tachycardia.An electrophysiological study was performed without inducing either ventricular or supraventricular arrythmia.
Serological screening for Trypanosoma cruzi was negative.Furthermore, there was no α-1-antitrypsin enzyme deficiency.The patient had no skeletal, vascular, or ophthalmologic signs suggestive of connective tissue disease.
We concluded that our patient has a LV apical aneurysm with a normal coronary artery.After one year of follow up his condition did not improve even with the introduction of an ACE inhibitor for mildly reduced ejection fraction.

Discussion
The patient's echocardiography revealed an apical outpouching consistent with a myocardial aneurysm or pseudoaneurysm.Differentiation between these two entities can be challenging.An aneurysm is an outpouching containing a thin myocardial layer.Pseudoaneurysm represents a pericardial-covered cardiac rupture, as such; it does not include a myocardial layer 1 .Cardiac CT scan and CMR helped us establish the diagnosis of an apical aneurysm by visualizing a thin myocardial layer.
There are ischemic and non-ischemic causes of apical aneurysm.The most common cause of apical aneurysm is myocardial infarction 1 .Coronary angiography showed normal coronary arteries, and CMR showed no signs suggestive of ischemic myocardial disease.Regarding the non-ischemic causes, α-1-antitrypsin enzyme deficiency is associated with pulmonary emphysema, and spontaneous pneumothorax and, in rare cases, may be associated with ventricular pseudoaneurysm 2 .The patient's chest CT showed severe emphysema for his age, and he had a spontaneous pneumothorax a year earlier.
Therefore, the level of α-1-antitrypsin enzyme was determined and was within the normal range.The patient underwent a comprehensive autoimmune and infectious serology assessment.We found no evidence of an autoimmune disease (negative anti-nuclear antibody and anti-neutrophil cytoplasmic antibody) or evidence of connective tissue disease (normal ophthalmologic and physical examination, an aortic root within normal range on echocardiography, and normal thoracic aorta on the CT-scan).Infectious serology screening, including serology for Trypanosoma cruzi, was negative.As a reminder, the patient had a history of invasive systemic tuberculosis, and the aneurysm may be consistent with a mycotic aneurysm   as a complication of systemic tuberculosis 3 .However, the CMR did not showed any arguments in favor of a left ventricular aneurysm secondary to a myocarditis, such as gadolinium late enhancement.Another hypothesis for the etiology could be a congenital LV aneurysm, which contrasts with the familial history of sudden death.
However, after reviewing the imaging studies, we found that the patient had marked prominent myocardial trabeculations localized at the level of the LV aneurysm, and met the Jenni criteria 4 for left ventricular non-compaction cardiomyopathy (LVNC): 1) thickened myocardium with a noncompacted inner layer and a compacted outer layer (Figure 5), 2) the ratio of the systolic thickness of the noncompacted to the compacted layer is greater than two in the parasternal short-axis view (Figure 5), 3) color Doppler evidence of deep intertrabecular recesses filled with blood from the LV cavity, 4) the typical distribution of affected segments includes the apical LV and the mid-lateral segment, as in our patient.(Figure 6).These findings were confirmed by Petersen criteria in CMR 5 (Figure 7).The family history of his father's sudden cardiac death supports this hypothesis.The results of genetic testing  excluded collagen defects and showed no mutation suggestive of LVNC, but as we know, genetic testing has a low diagnostic yield for LVNC 6 .
Treatment of heart failure with a mildly reduced ejection fraction was initiated with an ACE inhibitor, a beta blocker, and a SGLT-2 inhibitor, resulting in improvements of LVEF and symptoms.Defibrillator implantation was discussed but not yet performed, because the patient does not currently meet the criteria for a defibrillator.The patient has understood his illness well and has been compliant with all the investigations.However, currently, he does not see any significant improvement in his condition.
In conclusion, this young patient presents a LV apical aneurysm associated with a limited form of LVNC.This is a rare association, and to our knowledge, there are few similar cases in the literature to date.The diagnosis may be made in newborns 7 , in children 8 , in adults as in our case, or in older adults.This unusual combination of findings makes the case valuable for medical literature, as it adds to the understanding of diverse cardiac pathologies.The report demonstrates a thoughtful approach to ruling out potential causes of left ventricular aneurysm by considering both ischemic and non-ischemic etiologies.The inclusion of serological and genetic testing helps exclude various conditions, leading to a more accurate diagnosis.However, the case report does not include long-term follow-up data to assess disease progression over time.Although we provide a comprehensive assessment, the exact cause of the left ventricular aneurysm and the association with limited form of LVNC remains uncertain.A larger sample size or case series would be needed to draw more robust conclusions and further support the observed association between the left ventricular aneurysm and limited form of LVNC.
Overall, our case report offers valuable insights into a rare cardiac condition, utilizing multiple diagnostic techniques and considering various potential causes.However, it would benefit from long-term follow-up data and a larger sample size to enhance the generalizability of the findings and explore potential causality in this unique association.

Consent
Written informed consent for publication of their clinical details and clinical images was obtained from the patient.

Daniela Corina MIRICA
Hopital Delta, Auderghem, Bruxelles, Belgium The manuscript under review presents a medical case with significant academic potential.However, there are several areas requiring attention and improvement.Below are detailed observations and suggestions for revision.

Background and Abstract:
The background section duplicates the abstract without providing additional context or depth to the research question or the case's significance.A more distinct background section is necessary to set the stage for the case presentation, outlining the current understanding and gaps in knowledge regarding the topic.

Necessity of Coronary Angiogram:
The manuscript lacks a comprehensive explanation of the need for a coronary angiogram in the context of alternative non-invasive imaging modalities, especially for a low-risk patient for coronary artery disease (CAD).It is crucial to justify the choice of invasive diagnostic methods over non-invasive options, considering the patient's risk profile and existing literature on the subject.

Structure of Case Presentation:
The structure of the case presentation requires refinement.It should systematically follow the sequence of events, from the initial presentation through all diagnostic procedures to the final diagnosis, ensuring clarity and logical flow.Each finding from various explorations, such as MRI results and genetic testing, should be detailed within the case report section to provide a comprehensive overview of the patient's condition and the diagnostic journey.

Discussion on Diagnostic Hypotheses and Differential Diagnosis:
The discussion section begins with the main diagnostic hypothesis but lacks a robust argumentative foundation to support it.It should include a detailed analysis of why this hypothesis was considered over others, supported by evidence from the case and relevant literature.Following this, a thorough differential diagnosis should be presented, comparing and contrasting the case with similar reports in the literature to contextualize the findings and the decision-making process.Case Report Description: All findings, particularly those from MRI and genetic testing, need to be more comprehensively described within the case report section.This detail will enrich the case's educational value, allowing readers to understand the diagnostic significance of these tests fully.

Conclusion and Recommendations for Revision:
While the case presents an interesting scenario with potential for significant academic contribution, it requires major modifications to enhance its clarity, depth, and educational value.The authors are encouraged to: Distinguish the background from the abstract with additional context.1.
Justify the use of coronary angiogram in a low-risk patient for CAD, especially in the presence of non-invasive alternatives.

2.
Reorganize the case presentation for a clearer, chronological depiction of findings and diagnoses.

3.
Expand the discussion to include a stronger foundation for the main diagnostic hypothesis and a detailed differential diagnosis.

4.
Provide a more detailed description of all findings, especially those from MRI and genetic testing, within the case report section.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly

Is the case presented with sufficient detail to be useful for other practitioners? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: cardiology, non-invasive imaging I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Akinori Higaki
Ehime University, Toon, Japan In this report, the authors present a case of left ventricular non-compaction cardiomyopathy (LVNC) with associated apical aneurysms amidst prominent trabeculations.Given the rarity of this combination, their detailed report significantly contributes to the field of medicine.However, the reviewer notes several minor shortcomings that merit improvement.Regarding the manuscript's structure, it is unusual to include case descriptions in the Discussion section, especially when referencing specific figures like Figures 5, 6, and 7.These descriptions would be more suitable in the case report section.The Discussion section should instead focus on analytical discussions.
Finally, the reviewer suggests modifying the manuscript title to a more direct expression.For example, consider stating that the case report discusses a left ventricular aneurysm associated with LVNC.This change will help broaden the readership.".The reviewer suggests a more direct approach, such as stating that the case report discusses a left ventricular aneurysm associated with LVNC.The reviewer suggests a more direct approach, such as stating that the case report discusses a left ventricular aneurysm associated with LVNC.description of the diagnostic process, including the rationale for each test and the interpretation of results, provides valuable insights for medical education and clinical practice.However it would be useful to mention the recent critical reassessment of the condition as per the recent guidelines from 2023 which challenge the use of LVNC as a definitive cardiomyopathy diagnosis.Reviewer Expertise: cardiomyopathy I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
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Figure 1 .
Figure 1.ECG at the initial visit.

Figure 5 .
Figure 5. Transthoracic echocardiography demonstrates a ratio of the systolic thickness of the noncompacted (yellow line) to compacted layer (white line) greater than two in the parasternal short axis view.

Figure 6 .
Figure 6.Distribution of the trabeculations at the level of the LV apical aneurysm (white arrow) and the mid-lateral segment (yellow arrow).

Firstly, the
authors mention α-1-antitrypsin enzyme deficiency as a cause of non-ischemic etiology of ventricular aneurysms, but there are other common etiologies such as cardiac sarcoidosis and hypertrophic cardiomyopathy.Additionally, MINOCA (myocardial infarction with non-obstructive coronary arteries) can be considered an ischemic etiology of aneurysm.The discussion on etiology could be enriched by referencing previous literature, for instance, Shan et al [Ref 1].

References 1 .
Shan S, He X, He L, Wang M, et al.: Coexistence of congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LDB3 mutation: a case report.J Med Case Rep. 2017; 11 (1): 229 PubMed Abstract | Publisher Full Text Is the background of the case's history and progression described in sufficient detail?Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly Is the case presented with sufficient detail to be useful for other practitioners?Partly Competing Interests: No competing interests were disclosed.

References 1 .
Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, et al.: 2023 ESC Guidelines for the management of cardiomyopathies.Eur Heart J. 2023; 44 (37): 3503-3626 PubMed Abstract | Publisher Full Text Is the background of the case's history and progression described in sufficient detail?Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes Is the case presented with sufficient detail to be useful for other practitioners?Partly Competing Interests: No competing interests were disclosed.