Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations

Background: Pulmonary arteriovenous malformations (PAVMs) generate a right-to-left shunt. Impaired gas exchange results in hypoxemia and impaired CO2 clearance. Most patients compensate effectively but a proportion are dyspneic, and these are rarely the most hypoxaemic. Aim: To test degrees of concurrent pathology influencing exercise capacity. Design: Replicate, sequential single centre, prospective studies. Methods: Cardiopulmonary exercise tests (CPET) were performed in 26 patients with PAVMs, including individuals with and without known airflow obstruction. To replicate, relationships were tested prospectively in an independent cohort where self-reported exercise capacity evaluated by the Veterans Specific Activity Questionnaire (VSAQ) was used to calculate metabolic equivalents at peak exercise (METS N = 71). Additional measurements included oxygen saturation (SpO2), forced expiratory volume in 1 second (FEV1), vital capacity (VC), exhaled nitric oxide (FeNO), haemoglobin and iron indices. Results: By CPET, the peak work-rate was only minimally associated with low SpO2 or low arterial oxygen content (CaO2=1.34 x SpO2 x haemoglobin), but was reduced in patients with low FEV1 or VC. Supranormal work-rates were seen in patients with severe right-to-left shunting and SpO2 80% predicted. VSAQ-calculated METS also demonstrated little relationship with SpO2, and in crude and CaO2-adjusted regression, were lower in patients with lower FEV1 or VC. Bronchodilation increased airflow even where spirometry was in the normal range: exhaled nitric oxide measurements were normal in 80% of cases, and unrelated to any PAVM-specific variable. Conclusions: Exercise capacity is reduced by relatively mild airflow limitation (obstructive or restrictive) in the setting of PAVMs

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, 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.165 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.There 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.Haemoglobin 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

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary 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.</p><p>Methodology</p><p>497 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.</p><p>Principal Findings</p><p>Sixty-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).</p><p>Significance</p><p>These 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.</p></div

Harvard Medical School Department of Global Health and Social Medicine COVID-19 seminar series: COVID and surgical, anesthetic and obstetric care.

On May 21, 2020, the Harvard Program in Global Surgery and Social Change (PGSSC) hosted a webinar as part of the Harvard Medical School Department of Global Health and Social Medicine's COVID-19 webinar series. The goal of PGSSC's virtual webinar was to share the experiences of surgical, anesthesia, and obstetric (SAO) providers on the frontlines of the COVID pandemic, from both high-income countries (HICs), such as the United States and the United Kingdom, as well as low- and middle-income countries (LMICs). Providers shared not only their experiences delivering SAO care during this global pandemic, but also solutions and innovations they and their colleagues developed to address these new challenges. Additionally, the seminar explored the relationship between surgery and health system strengthening and pandemic preparedness, and outlined the way forward, including a roadmap for prioritization and investment in surgical system strengthening. Throughout the discussion, other themes emerged as well, such as the definition of elective surgery and its implications during a persistent global pandemic, the safe and ethical reintroduction of surgical services, and the social inequities exposed by the stress placed on health systems by COVID-19. These proceedings document the perspectives shared by participants through their invited lectures as well as through the panel discussion at the end of the seminar

Triage assessment of cardiorespiratory risk status based on measurement of the anaerobic threshold, and estimation by activity limitation in patients with pulmonary arteriovenous malformations and hereditary haemorrhagic telangiectasia

BACKGROUND: Rapid triaging, as in the current COVID-19 pandemic, focuses on age and pre-existing medical conditions. In contrast, preoperative assessments use cardiopulmonary exercise testing (CPET) to categorise patients to higher and lower risk independent of diagnostic labels. Since CPET is not feasible in population-based settings, our aims included evaluation of a triage/screening tool for cardiorespiratory risk. METHODS: CPET-derived anaerobic thresholds were evaluated retrospectively in 26 patients with pulmonary arteriovenous malformations (AVMs) who represent a challenging group to risk-categorise. Pulmonary AVM-induced hypoxaemia secondary to intrapulmonary right-to-left shunts, anaemia from underlying hereditary haemorrhagic telangiectasia and metabolic equivalents derived from the 13-point Veterans Specific Activity Questionnaire (VSAQ) were evaluated as part of routine clinical care. Pre-planned analyses evaluated associations and modelling of the anaerobic threshold and patient-specific variables. RESULTS: In the 26 patients (aged 21-77, median 57 years), anaerobic threshold ranged from 7.6-24.5 (median 12.35) ml.min-1kg-1 and placed more than half of the patients (15, 57.7%) in the >11 ml.min-1kg-1 category suggested as lower-risk for intra-abdominal surgeries. Neither age nor baseline SpO2 predicted anaerobic threshold, or lower/higher risk categories, either alone or in multivariate analyses, despite baseline oxygen saturation (SpO2) ranging from 79 to 99 (median 92)%, haemoglobin from 108 to 183 (median 156)g.L-1. However, lower haemoglobin, and particularly, arterial oxygen content and oxygen pulse were associated with increased cardiorespiratory risk: Modelling a haemoglobin increase of 25g.L-1 placed a further 7/26 (26.9%) patients in a lower risk category. For patients completing the VSAQ, derived metabolic equivalents were strongly associated with anaerobic threshold enabling risk evaluations through a simple questionnaire. CONCLUSIONS: Baseline exercise tolerance may override age and diagnostic labels in triage settings. These data support approaches to risk reduction by aerobic conditioning and attention to anaemia. The VSAQ is suggested as a rapid screening tool for cardiorespiratory risk assessment to implement during triage/screening