Pneumolysis and “silent hypoxemia” in COVID-19

COVID-19 severe lung compromised patients often evolve to life-threatening hypoxia. The mechanisms involved are not fully understood. Their understanding is crucial to improve the outcomes. Initially, past-experience lead to the implementation of standardized protocols assuming this disease would be the same as SARS-CoV. Impulsive use of ventilators in extreme cases ended up in over 88% fatality. We compare medical and physiological high altitude acute and chronic hypoxia experience with COVID-19 hypoxemia. A pathophysiological analysis is performed based on literature review and histopathological findings. Application of the Tolerance to Hypoxia formula = Hemoglobin/PaCO2 +3.01 to COVID-19, enlightens its critical hypoxemia. Pneumolysis is defined as progressive alveolar-capillary destruction resulting from the CoV-2 attack to pneumocytes. The adequate interpretation of the histopathological lung biopsy photomicrographs reveals these alterations. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are described. At high altitude, normal low oxygen saturation (SpO2) levels (with intact lung tissue and adequate acid-base status) could be considered silent hypoxemia. At sea level, in COVID-19, the silent hypoxemia starting at SpO2 =< 90% (comparable to a normal SPO2 {88-92%} at 3,500m) suddenly evolves to critical hypoxemia. This, as a consequence of progressive pneumolysis + inflammation + overexpressed immunity + HAPE-type edema resulting in pulmonary shunting. The proposed treatment is based on the improvement of the Tolerance to Hypoxia (Hemoglobin factor), inflammation reduction, antibiotics, rehydration & anticoagulation if required. Understanding the pathophysiology of COVID-19 may assist in this disease's management.

P1317 Very late onset of platypnoea orthodeoxia syndrome as first clinical scenario of patent foramen ovale

We report a case of a 83-year-old female, who had an admission for dyspnea. Laboratory showed D-dimer 1000 ng/ml, haemoglobin 12.4 mg/dL, CPR 0.08mg/dl whereas on Arterial Blood Gas test she had hypoxia with respiratory alkalosis. In view of suspected pulmonary embolism, she underwent Thoracic Computed Tomography scan that excluded it. During the stay the patient seemed more symptomatic while in standing position(with SpO2s 89% while supine plunging to 50% while standing): ABGs were performed both standing (reservoir 15 l/min pH 7.50, pO2 37.2 mmHg, pCO2 37.1 mmHg, HCO3 28.9 mmol/l) and recumbent position (reservoir 15 l/min pH 7.47, pO2 65.5 mmHg, pCO2 35.1 mmHg, HCO3 25.6 mmol), showing a difference of 28 mmHg. Subsequently the patient underwent v/p pulmonary scintigraphy: no signs of pulmonary embolism though it revealed a multiple focus of capitation Tc-99m macro aggregated albumin in brain, thyroid and kidneys (IMG top), compatible for veno-arterial shunt. Trans-esophageal echocardiography (TOE) revealed a massive stretched patent foramen ovale (PFO) with continuous right-to-left shunting through the atria. The bubble test (IMG bottom) confirmed the presence of patency along with sudden passage of microbubbles through the foramen. Qp/Qs = 0.8, due to volume overload in the left atrium from the right atrium. The imaging along with clinical scenario confirmed the suspected diagnosis of platypnea-orthodeoxia, finding the patent foramen ovale as the anatomical cause. Platypnea-orthodeoxia syndrome is a clinical condition characterized by dyspnea. Typically blood oxygen saturation declines with standing position while it resolves with recumbent. The classification entails 3 groups: intracardiac shunting (most common presentation), pulmonary shunting, ventilation-perfusion mismatch. Presence of multiple focus of albumin macroaggregates outside the lungs in v/p scintigraphy examination is suggestive for veno-arteriuous shunt: without shunt, normally all the albumin aggregates are hampered in the lungs’ field. Images in bottom are taken in sequence from a single acquisition during the TOE, in one single cardiac beat. Here is depicted the evidence of the PFO, the influx of bubbles in the right atrium and the instantaneous and massive shunt of the bubbles across the interatrial septum, in the left atrium. Usually the diagnosis is performed within 55 years old: it is interesting how late the diagnosis occurred in this patient with such resounding clinical manifestation. Top Scintigraphy with ventilation and perfusion lung scan sequences. Next, scintigraphy with capitation of Tc-99m macro aggregated albumin in brain, thyroid and kidneys. Bottom, Transesophageal echocardiogram: images taken within the same heart beat proving right-to-left passage of bubble across the septum. Abstract P1317 Figure. Scintigraphy and Transesophageal echo

Pulmonary transit of contrast during exercise is related to improved cardio-pulmonary performance in highly trained endurance athletes

Background The mechanisms underlying the high interindividual variability demonstrated for right-ventricular (RV) adaptation to exercise have not yet been identified, but different pulmonary vascular adaptations among individuals could be involved. Pulmonary transit of agitated saline (PTAS) during exercise has been demonstrated to be a good estimator of vascular reserve. Aim The aim of this study was to evaluate the presence of PTAS among endurance athletes (EAs) of both sexes and its influence on RV adaptation to exercise. Methods A total of 100 highly trained EAs performed a maximal cardiopulmonary exercise test. Bi-ventricular functional and structural characteristics as well as PTAS were evaluated at baseline and at peak exercise. Athletes were distributed between two groups based on the amount of PTAS during exercise as high (HTPAS; >12 bubbles) and low (LPTAS; ≤12 bubbles). Results Overall, 11 EAs exhibited an intra-cardiac shunt at rest and 1 met the criteria for chronic pulmonary disease and were excluded from the study. Among the remaining 88 EAs (51% women), 47 (53%) athletes were classified as HPTAS and 41 (47%) as LPTAS. HPTAS capability was associated with significantly larger RV contractile reserve, larger pulmonary vascular reserve and an enhanced maximal exercise capacity. On multivariate analysis, females were the only independent correlate of the HPTAS capability. Conclusion In highly trained endurance athletes, a HPTAS capability during exercise corresponded to an increase in pulmonary vascular and RV contractile reserves as well as an enhanced maximal exercise capacity. The long-term clinical or performance implications of the absence or presence of pulmonary shunting, and the subsequent RV afterload increase while performing exercise, remains to be determined.

Pulmonary arterial hypertension in adult congenital heart disease

Pulmonary arterial hypertension (PAH) is commonly associated with congenital heart disease (CHD) and relates to type of the underlying cardiac defects and repair history. Large systemic to pulmonary shunts may develop PAH if untreated or repaired late. PAH, when present, markedly increases morbidity and mortality in patients with CHD. Significant progress has been made for patients with Eisenmenger syndrome in pathophysiology, prognostication and disease-targeting therapy (DTT), which needs to be applied to routine patient care. Patients with PAH–CHD and systemic to pulmonary shunting may benefit from late defect closure if pulmonary vascular resistance (PVR) is still normal or near normal. Patients with PAH and coincidental defects, or previous repair of CHD should be managed as those with idiopathic PAH. Patients with a Fontan circulation, despite not strictly fulfilling criteria for PAH, may have elevated PVR; recent evidence suggests that they may also benefit from DTT, but more data are required before general recommendations can be made. CHD–PAH is a lifelong, progressive disease; patients should receive tertiary care and benefit from a proactive DTT approach. Novel biomarkers and genetic advances may identify patients with CHD who should be referred for late defect closure and/or patients at high risk of developing PAH despite early closure in childhood. Ongoing vigilance for PAH and further controlled studies are clearly warranted in CHD.

A case of ruptured sinus of Valsalva aneurysm and reversible flow-induced pulmonary hypertension

Pulmonary hypertension (PH) in adults with congenital heart disease (CHD) and significant systemic-to-pulmonary shunting is a significant cause of morbidity and mortality. Its pathophysiology is incompletely understood, but involves a flow-induced pulmonary arteriopathy characterized by endothelial cell dysfunction and vascular remodeling that alters pulmonary arterial vasoreactivity. There is a paucity of literature linking PH with left-to-right shunting due to ruptured sinus of Valsalva aneurysms (SOVA). We present a unique case of reversible, flow-associated PH due to a ruptured congenital right SOVA fistulizing into the right atrium (RA), with emphasis on non-invasive and invasive assessment of pulmonary hemodynamics before and after surgical intervention.

Severe Hepatic and Pulmonary Involvement in Rendu-Osler-Weber Syndrome

We report the case of a young woman with hereditary hemorrhagic telangiectasia (HHT) with severe liver involvement and pulmonary shunting. The medical imaging in this patient illustrates the severe shunting that can occur in these patients who often are asymptomatic. By showing this case, we want to highlight the role of liver transplantation in HHT with hepatic involvement.

E.N. Meshalkin (1916–1997) and its priority in the creation of the world’s first successful cavo-pulmonary anastomosis in clinic

<p>The idea of the cavo-pulmonary anastomosis originated simultaneously with US surgeons (A. Blalock), Italy (C. Carlon), the USSR (A. Bakulev) and Hungary (F. Robiczek). The first cavo-pulmonary shunting in several modifications in the experiment were carried out by C. Carlon in the late 1949 – early 1950s. The first two unsuccessful operations in clinic were performed by the American surgeon H. Shumacker until November 1954. Priority of the first in the world series of successful operations in clinic belongs to E.N. Meshalkin (from April 3 to October 1956). In a sense, its success was due to experimental research carried out in the autumn of 1955 – in the spring of 1956 by N.K. Galankin, T.M. Darbinian and D.A. Donetsky. However, until August 1956 N.K. Galankin and his colleagues objectively were not ready to introduce the cavo-pulmonary anastomosis into the clinic. The first successful cavo-pulmonary shunt in the USA on February 25, 1958 was carried out by W. Glenn. The author's experience, his authority and publication in a prestigious journal led to the fact that the cavo-pulmonary anastomosis in literature is usually called Glenn procedure. We believe, however, that it is more correct to call it the Bakulev–Meshalkin operation or Russian anastomosis.</p><p>Received 17 July 2017. Accepted 13 August 2017.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p>

Unexplained Hypoxia and Shunting on Echocardiography in Patients with Sickle Cell Disease: A Retrospective Review

Introduction: During an episode of vaso-occlusive crisis, some patients with sickle cell disease may develop a transient hypoxemia. While frequently attributed to acute chest syndrome or pulmonary embolism, clinically a portion of patients develop hypoxemia without a clear etiology. On echocardiography, some patients were noted to have Patent Foramen Ovale (PFO) and others were noted to have intrapulmonary shunting. We sought to further characterize this clinical finding in sickle cell patients. Methods: We conducted a single institution retrospective chart review from 2008 through 2015 to evaluate the incidence of pulmonary shunting and PFOs in patients with SCD, as demonstrated on an echocardiography. We further characterize each of these episodes with clinical and laboratory findings at the time of the event. The presence of absence of shunting and type of shunting was further verified by a single cardiologist reviewing all episodes. Kruskal-Wallis test or Fisher's exact test was used to compare characteristics between patients with intracardiac or intrapulmonary shunting. Results: A total of 36 (18 female (F), 18 male (M)) of the 352 (10%) patients seen at the Ohio State Comprehensive Sickle Cell Center were noted to have shunting on their echocardiogram reported over the 7 year time period. Independent review by cardiology confirmed the presence of a shunt in 32 patients (9%, 95% CI: 6-13%) (15F, 17M). The median age at the time of reporting was 29 (range: 18-51 yrs). Shunting was observed in patients of all genotypes (94% SS/SB0; 6% SC/SBeta+). Fourteen (6 F, 8 M) of the thirty-two (44%, 95% CI: 26-62%) patients under study were noted to have cardiac shunting and eighteen (9 F, 9 M) (56%, 95% CI: 38-74%) were noted to have pulmonary shunting. In the patients with cardiac shunting, all 14/14 were confirmed to have a PFO by independent cardiac review. At the time of echo, 27/32 (87%) were hospitalized and 19/32 (59%) had clinical hypoxia on the day of the echocardiography. Patients with cardiac shunting tended to have higher proportion of hypoxia compared with patients with pulmonary shunting (71% vs. 50%). 19/32 (59%) had concurrent CT angiography and 1/32 (5%) patients was confirmed to have a pulmonary embolism. This patient demonstrated a concurrent PFO. 9 (28%) had a concurrent diagnosis of acute chest syndrome (4 with cardiac shunting and 5 with pulmonary shunting). The median value of TR jet velocity at baseline was 2.64 (range: 2.0-4.0) (n=18) and the median TR jet velocity at the time of event was 2.67 m/s (range: 2.0-3.8 m/s) (n=27). In the cardiac shunting group, the TR jet velocity was 2.85 m/s (range: 2.0 -3.27m/s) and in the pulmonary shunting group, the TR jet velocity was 2.6 m/s (range: 2.2-3.8 m/s). Conclusion: Patients with SCD presenting with increasing hypoxia may have intracardiac or intrapulmonary shunting. A patent foramen ovale that opens during vaso-ossclusive crisis may cause transient hypoxemia. This opening is thought to be due to increasing pulmonary pressures. While the long term implications of this finding are currently being studied, intracardiac shunting should be considered in the differential of patients with SCD presenting with increasing hypoxia of unclear etiology. Disclosures No relevant conflicts of interest to declare.