Contrast Transcranial Doppler in Detection of Platypnea-Orthodeoxia Syndrome: A Key Clue for a Tricky Diagnosis

Discussion: Transcranial Doppler study can be a useful and effective tool for the clinicians to demonstrate the presence of a right-to-left shunt related to a patent foramen ovale and support clinical decisions in patients with a platypnea-orthodeoxia syndrome. This is a complex clinical entity, in which several pathophysiological mechanisms may be involved, so that a careful comprehensive evaluation of the patients is mandatory for a correct management.


Introduction
The platypnea-orthodeoxia syndrome (POS) is a rare clinical entity characterized by the development of dyspnea in the assumption of the upright position (platypnea), associated with arterial desaturation (orthodeoxia), defined as a drop in PaO 2 >4 mmHg or peripheral oxygen saturation (SpO 2 ) >5%, both resolved with recumbency [1]. The diagnosis of POS can be complex and is often missed; accordingly, a high grade of suspicion and appropriate investigation are required to achieve the correct diagnosis. In addition, the diagnostic tools at present recommended for the identification of the syndrome may be expensive and/or inapplicable in several patients. Herein we report a case of POS in which contrast transcranial Doppler (cTCD) ultrasonography allowed to achieve the correct diagnosis and management.

Case Presentation
A 24-year old woman was admitted to our emergency room complaining of worsening dyspnea (New York Heart Association class III). Her past medical history was significant for an acute lymphatic leukemia when she was 1-year old, treated with chemotherapy, radiotherapy (involving the chest and head) and bone marrow transplant when she was 2-year old. She was regularly taking thyroid hormones (levothyroxine) and an oestrogen-progestin pill because of panhypopituitarism. On physical examination, her blood pressure was 110/70 mmHg, heart rate 98 beats per minute and SpO 2 96% with a respiratory rate of 20 breaths per minute. Chest and cardiac auscultation revealed a diffuse reduction of vesicular murmur and a fixed split of the second heart tone, respectively. An electrocardiogram showed sinus tachycardia with T-wave inversion in the precordial leads and chest X-ray showed a widespread thickening of the bronchial walls, an enlarged cardiac image and kyphoscoliosis. A careful assessment of symptoms revealed that the patient's dyspnea was accentuated by the assumption of the upright position.
The patient, therefore, underwent multiple sequential arterial blood gas analyses that revealed a marked oxygen desaturation, associated with dyspnea, and sometimes with cyanosis, by passing from a supine to an orthostatic position. Symptoms rapidly disappeared and oxygen saturation normalized with recumbency.
Of note, orthostatic oxygen desaturation was not improved by O 2 administration. Based on these findings, POS was suspected.

Discussion
The mechanism of hypoxia in POS is usually the result of a mixing in the left atrium of deoxygenated venous blood coming from the systemic circulation with the oxygenated blood coming from the pulmonary circulation because of a right-to-left atrial shunt, related to the presence of a PFO. Typically, however, the shunt occurs only when the patient assumes an upright position [2], thus indicating that some functional abnormality favoring a pressure gradient between the right and left atrium is required, in presence of the anatomical defect, for the syndrome becomes manifest. Of note, in our patient multiple pathophysiological mechanisms concurred to cause the manifestation of the syndrome, with CTEPH having a major role in its development, as shown in Figure 2. In keeping with the complexity of the pathophysiologic mechanisms, the diagnosis of POS is often challenging and may actually be missed, so that the prevalence of the syndrome is probably underestimated. According to the most recently suggested diagnostic workup, the first step for the diagnosis is the assessment of oxygen blood saturation both in the lying and standing position, followed by a bubble contrast transthoracic echocardiogram that may identify an intracardiac shunt [3]. If transthoracic echocardiogram is inconclusive, a transesophageal echocardiogram should be performed to look for the presence of an intracardiac defect [4]. The diagnostic assessment can be completed with a cardiac magnetic resonance and computed tomography angiography, a V/Q scan for extra-pulmonary shunt [5], or invasive pulmonary arteriography when intra-pulmonary shunts are to be conformed or excluded [6]. In our case, a crucial test to achieve correct diagnosis of POS was cTCD, which only allowed the documentation of a clear and sizeable right to left shunt when the patient went from the supine to the standing position, in association with a relevant blood oxygen desaturation. Accordingly, we suggest that cTCD should be included in the diagnostic work-up of POS, even due to its simplicity, non-invasive character, low cost, and large availability, in particular when other tests are unreliable because of a not optimal ultrasound window or because not feasible for any reason [7,8].

Consent
The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with COPE guidance.