Hoarseness Due to Aortic Arch Aneurysms

Objective To give an overview of the Ortner’s syndrome caused by an aortic arch aneurysm. Methods By comprehensive retrieval of the pertinent literature published in the past two decades, 75 reports including 86 patients were collected and recruited into this study along with a recent case of our own. Results The aortic arch aneurysms causing hoarseness were most commonly mycotic aneurysms. In this patient setting, in addition to the left recurrent laryngeal nerve, trachea was the most commonly affected structure by the aortic arch aneurysm. Surgical/interventional/hybrid treatments led to a hoarseness-relieving rate of 64.3%, much higher than that of patients receiving conservative treatment. However, hoarseness recovery took longer time in the surgically treated patients than in the interventionally treated patients. Conclusion The surgical and interventional treatments offered similar hoarseness-relieving effects. Surgical or interventional treatment is warranted in such patients for both treatment of arch aneurysms and relief of hoarseness.


INTRODUCTION
In 1897, Ortner described a series of three cases of mitral stenosis who were also suffering from hoarseness of voice because of left recurrent laryngeal nerve palsy, and it was then termed as Ortner's syndrome [1] . This condition is rare, and its incidence is difficult to ascertain. The cardiovascular etiologies of hoarseness can be congenital, valvular, aortic, or supra-aortic vascular disorders [2] . Aortic aneurysm of any etiology can be a risk factor leading to cardiovascular hoarseness, whereas thoracic aortic aneurysms represent only 5% of the cases [2] . Nevertheless, Ortner's syndrome caused by an aortic arch aneurysm is an even rarer entity, and its clinical features, treatments of choice, and patients' outcomes are unknown although sporadic cases are continuously reported. The purpose of this study is to give an overview of the Ortner's syndrome caused by an aortic arch aneurysm.
In 27 (31.0%) patients, the exact locations of the arch aneurysm were described. Most of the aneurysms affect the distal portion of the aortic arch ( Table 2).
The etiology of the aneurysmal formation was described in 28 (32.2%) patients, with mycotic arch aneurysm being a major etiology ( Table 3).
The data independently extracted from each study were the study population; demographics; clinical symptoms; associated disorders; the size, shape, dimension, extension, location, and nature of the arch aneurysms; treatment of choice; hoarseness recovery; and patients' outcomes.
The IBM SPSS Statistics 22.0 software was used for statistical analysis. The measurement data were expressed in mean±standard deviation and were compared by independent sample/paired t-test. The categorical variables were compared by Fisher's exact test. The predictive risk factors for compression of other adjacent organs/tissues were assessed by multinomial logistic regression. P<0.05 was considered statistically significant.
Apart from compression of the left/right recurrent laryngeal nerve by the aortic arch aneurysm, 13 (14.9%) patients had compressions of other adjacent organs/tissues. The trachea was the most commonly affected organ (Table 4).
The predictive risk factors for compressions of other adjacent organs/tissues were assessed by admitting the size (P=0.059), shape (P=0.712), mural thrombus (P=0.410), and false aneurysm (P=0.999) as dependent variables by multinomial logistic regression. Only arch aneurysmal size was a quasi-determinant for the compressions.
In 32 patients, the hoarseness-relieving effect was reported: the hoarseness was relieved in 12 (37.5%) patients, improved in seven (21.9%) patients (improved by injection of hyaluronic acid for voice in one patient [74] ), and persisted in 13 (40.6%) patients (χ 2 =2.9, P=0.234). The total effective rate was 59.4% (19/32). The hoarseness recovery, improvement, and persistent rates did not differ between the surgical and interventional treatment groups (Table 5). However, the total effective rate of the patients receiving surgical/interventional/hybrid treatments was much higher than that of patients with conservative treatment (64.3% [18/28] vs. 0% [0/4], χ 2 =5.9, P=0.028). Time for hoarseness relief was much shorter in the interventionally treated patients than in the open surgically treated patients (Table 6).
Patients were on a follow-up of 8.3±7.2 months (n=25). Patients' outcomes were known for 59 patients: 36 (61.0%) patients recovered, one (1.7%) patient improved, four (6.8%) Indirect laryngoscopy becomes a more common technique for the diagnosis of vocal cord palsy. Further investigations include echocardiography, computed tomography, and magnetic resonance imaging. Early diagnosis of Ortner's syndrome is essential for starting timely treatment, restoring vocal cord function, and avoiding permanent damage of the patients.
The treatment of choice of aortic arch aneurysms can be an open surgery or an interventional procedure. Usually, the conventional treatment of mycotic aneurysms is open aneurysmectomy, along with the debridement of the adjacent infectious tissues. In situ tube graft insertion or extra-anatomic bypass grafting may be at risk of infection, and thus with less promising long-term outcomes [6] . In spite of advanced diagnostic modalities and refined interventional therapies of today, the mortality rate of surgical treatment of mycotic aneurysm remains high. Endovascular grafts have been widely used for the treatment of aortic aneurysms as a very appealing alternative to open aortic surgery, in particular for the patients in whom surgical procedures carry high risks [6] . The increasingly sophisticated interventional technology has enabled the treatment of lesions of the critical segments of the aorta, such as the thoracic and arch levels [6] .
The recovery in hoarseness is highly variable. In a comprehensive review including 58 patients with Ortner's syndrome, the hoarseness resolved in 44.8%, improved in 29.3%, persisted in 22.4%, and exacerbated in 3.5% of patients. The present study based on a cohort of patients with aortic arch aneurysm revealed a bit lower recovery and improving rates, but higher persisted rate of hoarseness. This might be explained by the fact that long-term compression of the left recurrent laryngeal nerve by an aortic aneurysm may take longer time to recover.
Morales et al. [28] described that aneurysm size increase but no endoleak was responsible for the persistent hoarseness after endovascular therapy of the aortic aneurysms, whereas aortic aneurysm size decrease was not necessarily associated with hoarseness relief after the procedure [28] . The present study illustrated that the surgical and interventional therapies offered similar hoarseness-relieving effects; and time for hoarseness relief was much shorter in the interventionally treated patients than in the surgically treated patients. It hinted that interventional therapy might be a treatment of choice that could lead to a higher hoarseness-relieving rate.

DISCUSSION
The left recurrent laryngeal nerve arises from the left vagus nerve at the level of the aortic arch curve, and then it curves around the aorta on the outer side of the ligamentum arteriosum ascending along the tracheoesophageal groove. This prolonged course makes it vulnerable to injury by the lesions of the surrounding structures [54] .
Hoarseness of voice is a frequent presentation of otolaryngology diseases due to a neoplastic, surgical, idiopathic, traumatic, central, or infectious etiology. Nevertheless, cardiovascular hoarseness, especially hoarseness due to an aortic arch aneurysm, is very rare. The bulging cardiovascular structures can frequently compress the left recurrent laryngeal nerve leading to left vocal cord paralysis, rendering patients presenting with hoarseness [2] .
In addition to hoarseness, the common symptoms of patients with Ortner's syndrome were dyspnea and dysphagia [72,73] . However, in this patient setting with an arch aneurysm as an etiology, the common symptoms were dyspnea, cough, and chest pain.
The etiology of thoracic aortic aneurysm can be typically categorized as heritable or degenerative. In the cohort of patients with Ortner's syndrome due to an aortic aneurysm, the underlying etiologies can be degenerative, traumatic, dissecting, and atherosclerotic, all pathological changes of the aorta that create compression on the left recurrent laryngeal nerve. In this report, mycotic infection prevailed the underlying causes of the aortic arch aneurysms, followed by an atherosclerotic etiology.
The aortic arch aneurysms lead not only to compression of the left recurrent laryngeal nerve, but also compression of other adjacent organs/tissues in one-fifth of the Ortner's syndrome patients, with the trachea being the most affected organ. Moreover, the arch aneurysmal size was found to be a quasideterminant leading to the adjacent organ compression as disclosed by the present study.

SMY
Substantial contributions to the conception or design of the work; acquisition, analysis, and interpretation of data for the work; drafting the work and revising it critically for important intellectual content; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; final approval of the version to be published No financial support. No conflict of interest.

CONCLUSION
Aortic arch aneurysms may cause compression of the left recurrent laryngeal nerve and other adjacent organs/tissues as well. The overall hoarseness-relieving (including recovery and improvement) rate of patients receiving non-conservative treatments was 64.3%, much higher than those with conservative treatment. However, hoarseness recovery took longer time in the surgically treated patients than in the interventionally treated patients. Surgical or interventional treatment is warranted in such patients for the treatment of arch aneurysms and for hoarseness recovery as well.