Morphometric aspects of studying the features of remodeling of atrial structures at postresection portal hypertension

Introduction. Removal of the left and right lateral lobes of the liver in white rats leads to postresection portal hypertension, which is characterized by dilation and plethora of the hepatic portal vein, mesenteric veins, esophageal and gastric veins, veins of the anterior abdominal wall, splenomegaly, ascites and multiorgan failure. Objective of the research: to study the features of remodeling of the structures of the atria at postresection portal hypertension histostereometrically. Materials of the research and their discussion. The peculiarities of remodeling the structures of the atria were histostoreometrically studied in 65 adult white male rats, which were divided into 3 groups: the 1- consisted of 20 intact animals, the 2 – 30 rats with postresection portal hypertension, which was modeled by removal of the left and right lateral lobes of the liver, the 3 – 15 animals with postresection portal hypertension and multiorgan failure. One month after the start of the experiment, rats were euthanized by bloodletting under conditions of thiopental anesthesia. Histological micropreparations were used to determine the diameters of cardiomyocytes of the left and right atria, diameters of their nuclei, nuclear-cytoplasmic relations, relative volumes of cardiomyocytes, capillaries, stroma, stromal-cardiomyocyte, capillary-cardiomyocyte relations, relative volumes of damaged cardiomyocytes. Quantitative indicators were processed statistically. Results of the research and their discussion. Histostereometrically, it was found that postresection portal hypertrophy leads to hypertrophy of atrial cardiomyocytes, their nuclei, growth of stromal structures, relative volumes of damaged cardiomyocytes, disorders of tissue and cellular structural homeostasis. The revealed features of remodeling of the studied structures dominated in the left atrium at combination of postresection portal hypertension with multiorgan failure. Conclusions. Postresection portal hypertension leads to pronounced remodeling of the structures of the left and right atria, characterized by hypertrophy of cardiomyocytes, changes in their nuclear-cytoplasmic relations, an increase of the relative volume of stroma, damaged cardiomyocytes, pronounced disorders of tissue and cellular structural homeostasis. The revealed morphological changes dominated in the left atrium at combination of postresection portal hypertension with multiorgan failure.

Left atrial septal pouch in a six-year-old child: echocardiographic and magnetic resonance view

In a 6-year-old child patient, transthoracic echocardiography revealed a large saccular structure (with anechogenic content) in the left atrium, near the fossa ovalis, and diagnosis of the left atrial septal pouch was made. The left atrial septal pouch is a kangaroo pouch-like structure on the left side of the interatrial septum, opened into the left atrial cavity without a connection between the left and right atria. It occurs when the foramen ovale is absent but the septum primum and septum secundum are only partially fused. The left atrial septal pouch is believed to be present in 47% of population. In many cases, the pocket on the atrial septum is small and it could not be detected by transthoracic echocardiography. Our description is uncommon because we diagnosed a very large septal pouch. Based on our knowledge, this is the youngest reported case of the left atrial septal pouch and the longest follow-up described in this type of congenital heart malformation.

Role of Phospholipases A2 in Vascular Relaxation and Sympatholytic Effects of Five Australian Brown Snake, Pseudonaja spp., Venoms in Rat Isolated Tissues

Human envenoming by Australian brown snakes (Pseudonaja spp.) may result in potentially life-threatening hypotension and subsequent cardiovascular collapse. There have been relatively few studies of the cardiovascular and sympathetic effects of Pseudonaja spp. venoms. In this study, we have examined the effects of venom from five brown snake species—P. affinis, aspidorhyncha, inframacula, nuchalis, and textilis—on cardiac inotropic and chronotropic responses, vascular tone, and sympathetic nerve-induced vascular contractions in rat isolated tissues. The role of phospholipases A2 (PLA2s) in venom-induced effects was assessed with the sPLA2 inhibitor varespladib. In rat isolated left and right atria, there were no physiologically relevant effects of Pseudonaja venoms (0.1–30 µg/ml) on left atrial force of contraction (inotropy) or right atrial rate (chronotropy). In contrast, in isolated small mesenteric arteries precontracted with a thromboxane mimetic, each of the five brown snake venoms (at 30 µg/ml) caused marked vasorelaxation (−60 to –90% of contractile tone). Pretreatment with varespladib (1 µM) significantly inhibited the vasorelaxation caused by P. aspidorhyncha, P. nuchalis, and P. textilis venoms. Electrically induced sympathetic nerve-mediated contractions of mesenteric arteries were significantly attenuated by only P. textilis, and P. affinis venoms (30 µg/ml) and these sympatholytic effects were inhibited by varespladib (1 µM). Based on their inhibition with the sPLA2 inhibitor varespladib, we conclude that PLA2 toxins in P. aspidorhyncha, P. nuchalis, and P. textilis venoms are involved in brown snake venom-induced vasorelaxation and the sympatholytic effects of P. affinis, and P. textilis venoms. Our study supports the promising potential role of varespladib as an initial (pre-referral) and/or adjunct (in combination with antivenom) therapeutic agent for brown snake envenoming.

Machine learning analysis of chest CT to detect cardiac abnormalities in COVID19

Introduction Standard, un-gated chest CT can be used as the basis of detailed segmentation of the atrial and ventricular cardiac chambers. In conditions such as COVID19 where dedicated cardiac imaging may be hazardous or unavailable atlas-based machine learning tools allow automatic quantification of cardiac morphology and may allow early detection of abnormalities. Purpose To develop an automated screening tool to detect cardiac changes associated with COVID19 on chest/lung CT to allow early treatment and appropriate selection of patients for dedicated cardiac imaging. Methods A previously validated atlas-based cardiac contouring algorithm was modified to work within the setting of variable and severe lung pathology. The modified technique was used to segment the left and right atria and ventricles from non-contrast CT scans. We applied the developed algorithm to the Moscow University COVID19 CT dataset. 1110 scans were available. COVID19 severity was graded 0 to 4. Grade 4 was not used in analysis due to insufficient numbers. Cardiac chamber sizes were compared according to COVID19 severity status. In a limited cohort of repeat studies, the feasibility of polar mapping to demonstrated serial morphological change was tested. Results A statistically significant increase of average cardiac chamber volumes was noted relative to mild Grade 0 COVID19 at every incremental severity grade (Figure 1). Changes in average ventricular volumes were greater (up to 15.2% and 16.9% for left and right ventricles) than changes in atrial volumes (up 12.1% and 7.6% for left and right atria). Automated quantification was successful in the large majority of cases and inter-patient polar mapping of sequential data to detect progressive chamber enlargement appears feasible (Figure 2). Conclusion Machine learning methods permit automatic quantification of cardiac chamber size from standard lung CT scans. Cardiac changes on lung CT examinations may be used to identify cardiac abnormalities at an early stage and could be useful to triage individuals for dedicated cardiac investigations. With further refinement, this method may be useful to detect and track temporal cardiac changes in COVID19, as well as in other pulmonary pathology and conditions in which chest CT is routinely used. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SPHERE Research consortium Figure 1 Figure 2

Atrial function discriminates paroxysmal AF patients with HFpEF from those without HFpEF: subanalysis from AF-RISK study

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie. Grant support from the Dutch Heart Foundation [NHS2010B233] Background. Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are two cardiovascular conditions that often coexist. Overlapping symptoms, biomarker profile, and echocardiographic changes hinder the diagnosis of underlying HFpEF in patients with AF and suggest that both conditions might reflect similar remodelling processes in the heart. Purpose. To assess cardiac remodelling in AF patients with versus without concomitant HFpEF by transthoracic echocardiography, focusing on atrial dimension and strain. Methods. We selected 120 patients included in AF-RISK, a prospective, observational, multicentre study aiming to identify a risk profile to guide atrial fibrillation therapy study. Patients had paroxysmal AF diagnosed within three years before inclusion, had a left ventricular ejection fraction (LVEF) ≥50% and were in sinus rhythm at the moment of performing echocardiography and blood sampling. Patients were matched by nearest neighbour by age and sex with a 1:1 ratio and were classified into two groups: 1) AF with HFpEF (n = 60) and 2) AF without HFpEF (n = 60). The diagnosis of HFpEF was based on the 2016 ESC heart failure guidelines, including symptoms and signs of heart failure, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥125pg/ml, and one of the following echocardiographic measures: left atrium volume index (LAVI) >34ml/m2, left ventricular mass index ≥115g/m2 for men and ≥95g/m2 for women, average E/e’ ≥13cm/s and average e’ <9cm/s. Measurements of reservoir, conduit and contraction strain of both atria were performed in apical four-chamber by echocardiography (GE, EchoPac BT12). Associations of clinical and echocardiographic characteristics were tested for collinearity by multivariable logistic regression analyses. LAVI, LV mass index and NT-proBNP were excluded from multivariable analysis since these markers were part of the HFpEF diagnostic criteria. Results. Patients with paroxysmal AF and concomitant HFpEF had more often hypertension (72% vs. 45%, P = 0.005), had more impaired strain phases of both the left and right atria (figure 1), had comparable LVEF and global longitudinal strain (GLS) (P = 0.168 and P = 0.212, respectively). In a model adjusted for the number of comorbidities and sex, LA contraction decrease was associated with presence of HFpEF (odds ratio per 1% LA contraction-percent was 0.94, 95% confidence interval 0.87–0.99, P = 0.042). LA contraction was not explained by LAVI in patients with concomitant HFpEF (Spearman’s rho= -0.07, P = 0.08). Conclusion. Our results show that atrial function may differentiate paroxysmal AF patients with HFpEF from those without HFpEF. In patients with paroxysmal AF, more impaired strain phases of the left and right atria were associated with concomitant HFpEF, whereas ventricular function, reflected by LVEF and GLS, did not differ. Abstract Figure. Strain distribution of both atria