Hoarseness as a Rare Symptom of Idiopathic Pulmonary Arterial Hypertension Due to Ortner Syndrome: A Case Report

Introduction

This case report highlights hoarseness as an atypical symptom of idiopathic pulmonary arterial hypertension (IPAH) due to Ortner syndrome, first noted by Nobert Ortner first in 1897 [1] and referring to hoarseness caused by paralysis of the left laryngeal nerve due to enlarged cardiovascular structures. While it is commonly associated with severe mitral stenosis and left ventricle enlargement, as initially described by Ortner, it can also be associated with other vascular structures, such as aortic aneurysm, aortic dissection, pulmonary artery dilatation, and enlarged mediastinal structures [2]. In this case report, we present a rare case of Ortner syndrome that was subsequently diagnosed as IPAH, with an enlarged pulmonary artery causing left recurrent laryngeal nerve palsy.

Case Report

A 32-year-old male patient was admitted to the Cardiology Department with suspicion of PAH. Two months before hospitalization, the patient developed hoarseness, which persisted for 3 weeks and prompted him to see his primary care physician. Initially, the patient was prescribed an inhaled steroid, but due to a lack of improvement, he returned to the doctor. During this visit, in addition to hoarseness, the patient reported a slight decrease in exercise tolerance, which had not bothered him earlier, due to his intense training for an upcoming triathlon competition. The primary care physician referred him to an otolaryngologist, who diagnosed paralysis of the left vocal fold, likely due to left recurrent laryngeal nerve palsy. Subsequently, the patient was referred to a pulmonology center. There, after conducting a differential diagnosis that included computed tomography, flexible fiberoptic endoscopy, and a cardiology consultation, the team suspected that compression of the left laryngeal nerve might be caused by a cardiopulmonary structure. As a result, the patient was urgently referred to our Cardiology Department.

Upon admission, his NT-pro BNP level was increased to 169 pg/mL (reference level <125 pg/mL). He reached a distance of 570 m in a 6-minute walk test. However, cardiopulmonary exercise testing showed low peak oxygen uptake of 16.4 mL/min/kg (39% of predicted value). Moreover, signs of right ventricle (RV) hypertrophy and overload were visible in ECG. Transthoracic echocardiography was performed and showed a high probability of pulmonary hypertension-enlarged RV (4CH, 55 mm) with basal RV/left ventricle (LV) ratio >1.0, flattened interventricular septum with LV eccentricity index of 1.62, decreased right ventricular outflow tract acceleration time of pulmonary ejection (87 ms), severe tricuspid regurgitation (5.45 m/s), dilatation of pulmonary artery (53 mm), decreased tricuspid annular plane systolic excursion to 16 mm, enlarged right atrial area (27 cm2), and presence of pericardial effusion up to 3 mm. Right heart catheterization was performed and indicated pre-capillary pulmonary hypertension, with mean right atrial pressure of 7 mmHg, mean pulmonary artery pressure of 109 mmHg, pulmonary artery wedge pressure of 10 mmHg, cardiac index of 2.7 L/min/m2, stroke volume index of 31.5 mL/m2, pulmonary vascular resistance of 17.6 Wood units, and mixed venous oxygen saturation of 69.3%, irreversible in the acute vasoreactivity test (mean pulmonary artery pressure, 92 mmHg). Then, several additional tests were performed to clear the causes of pulmonary hypertension. First, we excluded thromboembolic origin, and then, pulmonary tests were performed. There was no pathology in the computer tomography scan in the lung parenchyma, no mediastinal lymphadenopathy or signs of a proliferative process, spirometry was normal, body plethysmography was normal, diffusing capacity of the lungs for carbon monoxide showed mild impairment of CO2 transfer. The patient did not have any congenital heart disease or any left heart disease. Cardiac magnetic resonance imaging (Figures 1–3) was also performed, showing the right ventricle was enlarged, with increased trabeculation, with impaired contractility, and reduced ejection fraction (right ventricular ejection fraction, 38%; STROKE VOLUME INDEX, 41 mL/m2; pulmonary trunk dilated to 53 mm). A diagnosis of IPAH was made, and the patient started treatment with combined therapy of sildenafil, bosentan, and treprostinil, in increasing doses.

After several months of therapy, the patient was readmitted for follow-up tests. He was treated with combined therapy of sildenafil, bosentan, and treprostinil intravenously (IP 2000K Tricumed pump) at a dose of 70.73 ng/kg/min, with good treatment tolerance. The patient no longer experienced hoarseness and had no reports of concerns on admission. The patient reported that his vocal function partially recovered after 8 months of treatment and completely after about 10 months of treatment, allowing the patient to speak loudly and even shout, which we confirmed in an otorhinolaryngology consultation and flexible fiberoptic endoscopy, which revealed complete recovery of the left vocal fold paralysis. Exercise tolerance had improved (World Health Organization functional class I/II), and the patient reached an improved distance of 600 m in a 6-minute walk test. Cardiopulmonary exercise testing also showed improvement, with a better peak oxygen uptake of 23.1 mL/min/kg (65% of predicted value). His NT-Pro BNP level was decreased to 67 pg/mL (reference level <125 pg/mL). The echocardiographic examination also revealed improvement; however, it still showed a high probability of pulmonary hypertension, with an enlarged but smaller RV (4CH, 54 mm), with basal RV/LV ratio >1.0, flattened interventricular septum, with improved LV eccentricity index of 1.2, right ventricular outflow tract acceleration time of pulmonary ejection within the reference range (148 ms), moderate tricuspid regurgitation (4.95 m/s), less dilatated pulmonary artery (40 mm), increased tricuspid annular plane systolic excursion within the reference range to 23 mm, enlarged but smaller right atrial area (23 cm2), and no presence of pericardial effusion. Follow-up right heart catheterization was also performed and revealed improvement by mean right atrial pressure of 4 mmHg, mean pulmonary artery pressure of 73 mmHg, pulmonary artery wedge pressure of 5 mmHg, cardiac index of 4.0 L/min/m2, stroke volume index of 52 mL/m2, pulmonary vascular resistance of 7.3 Wood units, and mixed venous oxygen saturation of 73.4%. Another cardiac magnetic resonance imaging (Figures 1–3) was performed and demonstrated improved outcomes, including improved right ventricular ejection fraction of 46%, stroke volume index of 46 mL/m2, and a less dilated pulmonary trunk, measuring 49 mm.

All parameters showed improvement, with greater exercise tolerance and hoarseness remission in our patient, which seems to be a permanent effect, with no recurrence to date.

Discussion

IPAH is the most common type of arterial pulmonary hypertension [3], which is a rare disease that affects about 48 to 55 per million adults [4]. It usually presents with symptoms such as easy fatigability, dyspnea, chest pain, and syncope. While hoarseness is a rare symptom [5], there have been several, but limited, cases reported to be associated with IPAH [6]. To better understand the cause-effect relationship, it is important to study the anatomy of the left vagus nerve, which gives rise to the left recurrent laryngeal nerve at the level of the aortic arch, then loops posteriorly under the aortic arch and moves toward the neck in the canal between the esophagus and trachea, to finally stimulate the muscles controlling the left vocal cord. The relatively long way of the left recurrent laryngeal nerve makes it sensitive to compression [7]. Autopsy studies have shown that the distance between the aorta and pulmonary artery is only 4 mm, which suggests that compression of the nerve between the 2 structures accounts for causing palsy [8]. It is important to note that IPAH is a rare but significant cause of left recurrent laryngeal nerve palsy in young patients. Confirming the presence of a dilated pulmonary artery is essential for diagnosis. Pulmonary artery dilatation can lead to several complications, not only compression of the recurrent laryngeal nerve, resulting in hoarseness. Additionally, the dilatation can compress the left coronary artery, leading to chest pain during exertion, and, through compression of the bronchi, can cause shortness of breath, expiratory wheezing, coughing, and lower respiratory tract infections [9]. It is worth mentioning that paralysis can improve with the right treatment [6].

We present a very interesting case of a young man whose main symptom of IPAH was hoarseness. The patient remained asymptomatic for a long time, and his decrease in exercise tolerance was not noticeable, due to his initially high exercise tolerance. Despite achieving a high distance in the 6-minute walk test (570 m) upon admission, the results of right heart catheterization were crucial and forced us to implement aggressive treatment. Since rapid diagnosis and implementation of combined treatment is beneficial and improves long-term survival in patients with PAH [10], we offered our patent combination therapy with sildenafil, bosentan, and treprostinil in increasing doses, with good clinical outcome.

Our case highlights the importance of differential diagnosis and considering the possibility of PAH in patients presenting with non-specific symptoms, such as hoarseness. It is crucial to refer such patients for further assessment and appropriate treatment, as early intervention in those with less advanced disease can lead to better outcomes [11].

Conclusions

In conclusion, this case emphasizes the significance of including rare cardiovascular diseases such as IPAH in the list of potential causes of hoarseness. Hoarseness caused by the left recurrent laryngeal nerve palsy, resulting from pulmonary artery dilation, can be treated effectively with appropriate IPAH treatment.