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To the editor
Pulmonary arteriovenous malformations (PAVMs) result in hypoxaemia due to right-to-left shunting.1 Recent studies highlight that chronic hypoxaemia in iron-replete patients leads to secondary erythrocytosis which preserves arterial oxygen content (CaO2).2 Both shunt fraction3 and hypoxaemia severity4 may increase acutely on standing, a phenomenon ascribed to basally situated PAVMs.3 ,4 Platypnoea–orthodeoxia (dyspnoea and arterial deoxygenation on standing) has been described, particularly in patients with patent foramen ovale.5 However, platypnoea was not our experience in the PAVM population, suggesting they may be able to compensate for acute falls in CaO2. The goal of the study was to quantify orthodeoxia and examine potential compensatory mechanisms to facilitate provision of appropriate information to PAVM patients.
The study was ethically approved by the Hammersmith, Queen Charlotte's, Chelsea, and Acton Hospital Research Ethics Committee (LREC 2000/5764). Full methods are presented in the online supplementary data supplement. In all, 258 consecutive patients with CT-proven PAVMs were prospectively and newly recruited (2005–2013) and evaluated as described.1 ,2 Pulse and oxygen saturation (SaO2) were measured by pulse oximetry in supine and erect postures for 10 min. Exercise capacity was stratified to a modified Medical Research Council (MRC) dyspnoea scale, with individuals classified as grade 1a if they participated in intense sporting activity at least three times per week.2
Full patient demographics are presented in online supplementary Table 1. Ages ranged from 16 to 90 (median 48) years. A total of 89 (34.5%) were male. For 239 (92.6%), PAVMs were attributable to hereditary haemorrhagic telangiectasia (HHT). Overall, 50/221(22.6%) were obese with a body mass index>30. Comorbidities were more common in patients with higher grade dyspnoea (see online supplementary Figure 1). Replicate SaO2 and pulse values demonstrated high within-patient reproducibility (see online supplementary Table 2).
Overall, erect SaO2 was significantly lower than supine SaO2 (figure 1A). In 75/257 (29%) patients, the SaO2 fell by at least 2% on standing compared with the equivalent supine reading. A smaller fall of 1%–2% was present in a further 54/257 (21%) patients. None of these patients reported dyspnoea on standing (platypnoea), although one was unable to complete the 10 min standing due to dizziness. As expected, obese patients had lower supine SaO2 for their erect SaO2, and correspondingly less evidence of orthodeoxia (see online supplementary Figure 4).
Sudden falls in SaO2 reduce CaO2 per unit blood volume. However, there was a consistent increase in heart rate on standing (figure 1B). Orthostatic tachycardia was more pronounced in PAVM patients than 40 controls (figure 1C, and online supplementary Figures 2 and 3), and in patients exhibiting greater falls in SaO2/CaO2 (see online supplementary Figure 5). Postural orthostatic tachycardia is normally viewed in a detrimental manner, but in this study, more marked orthostatic tachycardia was observed in patients with better exercise tolerance (figure 1D), whether analysed in five groups as shown, or in three groups of athletes (grade 1a), normal (grade 1b) and all dyspnoeic patients (grades 2–4).
To conclude, we provide an extensive consecutive series demonstrating that orthodeoxia is common in PAVM patients, though may be masked by obesity. Exuberant postural orthostatic tachycardia may be part of acute compensatory mechanisms that maintain tissue oxygen delivery when CaO2 falls suddenly on standing, and is associated with better exercise tolerance in PAVM patients.
Funding was received from the National Institute of Health Research NIHR: London (NW) Comprehensive Local Research Network; patient donations; and Imperial College BSc project funds (to CLS for VS and BC).
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Files in this Data Supplement:
- Data supplement 1 - Online supplement
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