BackgroundPulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.Methodology497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.Principal FindingsSixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).SignificanceThese data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.
BackgroundOxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.Methodology165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.Principal FindingsThere was wide variation in SaO2 on air (78.5–99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.SignificanceHaemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses.
Increasing evidence supports the use of embolisation to treat pulmonary arteriovenous malformations (AVMs). Most pulmonary AVM patients have hereditary haemorrhagic telangiectasia (HHT), a condition that may be associated with pulmonary hypertension.The current authors tested whether pulmonary AVM embolisation increases pulmonary artery pressure (Ppa) in patients without baseline severe pulmonary hypertension. Ppa was measured at the time of pulmonary AVM embolisation in 143 individuals, 131 (92%) of whom had underlying HHT. Angiography/embolisation was not performed in four individuals with severe pulmonary hypertension, whose systemic arterial oxygen saturation exceeded levels usually associated with dyspnoea in pulmonary AVM patients.In 143 patients undergoing pulmonary AVM embolisation, Ppa was significantly correlated with age, with the most significant increase occurring in the upper quartile (aged .58 yrs). In 43 patients with repeated measurements, there was no significant increase in Ppa as a result of embolisation. In half, embolisation led to a fall in Ppa. The maximum rise in mean Ppa was 8 mmHg: balloon test occlusion was performed in one of these individuals, and did not predict the subsequent rise in Ppa following definitive embolisation of the pulmonary AVMs.In the present series of patients, which excluded those with severe pulmonary hypertension, pulmonary artery pressure was not increased significantly by pulmonary arteriovenous malformation embolisation.KEYWORDS: Brain abscess, hypoxaemia, nosebleeds, oxygen saturation, right-to-left shunt, stroke D oes embolisation of pulmonary arteriovenous malformations (AVMs) precipitate pulmonary hypertension (PH)? The reason this question is important is that for individuals with pulmonary AVMs, embolisation is an effective means of reducing lifetime risks of paradoxical embolic stroke and brain abscess [1,2], improving oxygenation [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] and treating pulmonary AVM-related haemoptysis [18,19]. Conversely, embolisation may be expected to elevate pulmonary artery pressure (Ppa), since pulmonary AVMs are abnormal dilated vessels between pulmonary arteries and veins that provide low resistance pathways for pulmonary blood flow [20].The question of whether pulmonary AVM embolisation increases Ppa is particularly pertinent, since most individuals with pulmonary AVMs have underlying hereditary haemorrhagic telangiectasia (HHT). Typically recognised by nosebleeds, mucocutaneous telangiectasia and visceral AVMs [21], HHT may be associated with PH [9,[22][23][24][25][26][27][28][29][30]. The secondary causes of PH in HHT are diverse, as they are in the normal population [31], but PH particularly occurs either as a true pulmonary arterial hypertension (PAH) phenotype [9,22,[28][29][30] or in the context of high output cardiac failure secondary to hepatic AVMs, when PH may be reversible after hepatic AVM treatment [32]. The frequencies of PAH and hepatic AVMs differ with HHT genotype: HHT is caused by mutatio...
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