Left Atrium Research Articles

Clinical outcomes and impact of mitral valve surgery in atrial functional mitral regurgitation: the REVEAL-AFMR registry

Abstract Background The real-world impact and effective treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. The aim of this study was to investigate the prevalence, clinical characteristics, and the effectiveness of mitral valve surgery in AFMR. Methods The REal-world obserVational study for invEstigAting the prevaLence and therapeutic options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR) was a retrospective cohort study conducted across 26 Japanese centers. All transthoracic echocardiography performed in 2019 were reviewed and patients with moderate or severe AFMR defined by preserved left ventricular function, dilated left atrium, and absence of degenerative valvular changes. The primary composite outcomes were heart failure hospitalization and all-cause mortality. Besides traditional multivariable regression analysis, propensity score-based time-zero matching was performed to account for immortal time bias. Results In 177,235 patients who underwent echocardiography, 8,867 had moderate or severe MR. Within this group, 1,007 were diagnosed with AFMR (mean age 78±10, 56% female, 80% atrial fibrillation). Of these, 113 underwent MV surgery, with 81% receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR, larger left heart chambers, and a higher prevalence of heart failure than those who remained under medical therapy. During a median follow-up of 1050 days, 28% experienced the primary outcome, and 18% died. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had significantly lower rate of the primary outcome (hazard ratio 0.43 [0.29-0.64], p<0.001 after adjustment for 25 covariates). Propensity score-based time-zero matching also indicated a lower risk of the primary outcome in the surgical group (hazard ratio 0.39 [0.20–0.78], p=0.007). Multiple sensitivity analyses yielded consistent results. Subgroup analysis suggested a significantly greater benefit of surgery for patients with severe MR than those with non-severe MR (p for interaction=0.044). Conclusions Our registry revealed that patients with AFMR are typically old with predominantly with atrial fibrillation, facing poor outcomes. MV surgery was associated with fewer adverse events, a finding that should be validated in future clinical trials.

Imaging predictors of adverse prognosis in fabry disease cardiomyopathy: a systematic review and meta-analysis

Abstract Background Cardiac involvement represents the main cause of death in patients with Fabry disease (FD). Echocardiography and Cardiac Magnetic Resonance (CMR) have an established diagnostic role, but their prognostic value remains unresolved. This systematic review and meta-analysis sought to assess the prognostic implications of imaging parameters in FD. Methods PubMed, ClinicalTrials.gov, Embase and Cochrane Library databases were searched for studies published from inception through to October 1, 2023. Full-length original papers including FD patients undergoing baseline imaging assessment and clinical follow-up were selected. Pre-defined study outcomes were a cardiovascular endpoint and a composite clinical endpoint. A meta-analysis of the studies investigating the effect of single imaging parameters on a pre-specified cardiovascular endpoint and a separate analysis on a pre-specified composite clinical endpoint were performed to obtain the pooled estimates for the association between the imaging parameters and the study outcome. The study protocol was registered in PROSPERO. Results Thirteen studies including 1,399 FD patients (44.8% males) were selected. At pooled analysis, late gadolinium enhancement (HR 4.39; 95% CI 2.5-7.71), left atrium volume indexed (HR 1.02 per ml/m2; 95% CI 1.01-1.04), E/e’ (HR 1.14 per unit increase; 95% CI 1.08-1.21), left ventricular (LV) mass indexed (HR 1.014 per mg/m2; 95% CI 1.006-1.023), maximum LV wall thickness (HR 1.19 per mm, 95% CI 1.04-1.36), LV-global longitudinal strain (HR 1.2 per unit increase; 95% CI 1.2-1.27), were significantly associated with the cardiovascular endpoint, whereas T1-mapping (p=0.115) and LV-ejection fraction (p=0.305) were not. T1-mapping was associated with the composite endpoint (HR 0.986 per msec increase; 95% CI 0.976-0.997). Meta-regression analysis did not show any significant interaction between each of the potential effect modifiers. Conclusion This meta-analysis demonstrates a robust prognostic value regarding several imaging parameters in FD, specifically indexes of LV mass and wall thickness, diastolic dysfunction, LV-GLS, and LGE presence. These findings support multimodality cardiovascular imaging, including CMR, in FD disease patients to predict long-term prognosis and call for longitudinal multicentre studies to develop multi-modality-imaging derived risk-score algorithms.

The potential protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients after one year of observation

Abstract Introduction Despite the widespread use of anthracyclines (ANT) and anti-HER2 agents as trastuzumab (TZB) in chemotherapy schemes, it is known the potential cardiotoxic effects that can limit the intensity and duration of treatments. The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus. Purpose We aimed to study if dapagliflozin could exerts cardioprotective effects in anthracycline, carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction (LVEF), global longitudinal strain (GLS) of both left and right ventricle, E/A ratio, E/e’ ratio, left atrium diameter, BNP/NT-pro-BNP and troponin I. Methods 32 diabetic patients were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function as well as chemotherapeutic agents ). Our patients who were diagnosed with cancer at our medical center, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Results In the first year of observation patients treated with dapagliflozin didn’t show any deterioration of LV GLS (¬19.8±2.8 vs ¬19.3±4.1%, p=0.403) There was no change in LVEF (57.8±4.9% vs 59±6.8%) and GLS of right ventricle (20.3±2.8% vs 20.0±3.6%). Conversely, patients treated with placebo, presented a significant impairment of LV GLS (¬20.8±2.1% vs ¬18.5±2.2%, p=0,001) while a borderline deterioration of EF was noticed after treatment with placebo(60±5.4 vs 56.7±6.7%, p=0,045). Conclusions At the best of our knowledge, our study is the first to investigate the prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in diabetic patients receiving anthracycline or trastuzumab,carflilzomib therapies. Treatment with dapagliflozin prevented deterioration of myocardial function and preserved ejection fraction

Organization of atrial flutter during pulse field ablation for atrial fibrillation

Abstract Background Pulse Field Ablation (PFA) has been acknowledged as an effective and safe tool for ablation of Atrial Fibrillation (AF). It is known that during AF ablation, the arrhythmia may organize into atrial flutter. The left atrial posterior wall is identified as a critical source of non-Pulmonary Vein (PV) triggers that facilitate maintenance of atrial fibrillation. Objective The purpose of this study is to investigate the phenomenon of atrial flutter organization from AF during the application of PFA. Methods This prospective multicentric study encompasses 117 consecutive patients with persistent AF across American and European institutions, undergoing first time catheter ablation. All receive isolation of the Pulmonary Veins (PV) plus Posterior Wall (PW) isolation. The PW isolation procedure targeted the standard area between the PVs and extended to the area demarcated by the line connecting the inferior borders of the inferior PV-encircling lesions to the coronary sinus defined lower part of PW (Fig. 1). The study documented the specific locations where AF organized into atrial flutter with a stable cycle length during PFA. Results Organization of AF to atrial flutter during PFA was observed in 72 (61.5%) patients. Analysis of the organization of flutter revealed that in 41 (56.9%) of these cases, flutter began while ablating the lower part of the PW. Moreover, 9 (12.5%) initiated at one of the PVs, and 22 (30.5%) during the ablation of the posterior wall. Notably, the flutter was described as perimitral flutter in 33 (45.8%), as typical flutter in 24 (33.3%), and as roof-dependent flutter in 15 (20.8%) of cases. Conclusion The findings underscore that during PFA for AF, there is a pronounced tendency for the arrhythmia to organize into atrial flutter, particularly during the ablation of the lower posterior wall. Notably ablation in the left atrium organized AF in typical atrial flutter at a considerable rate.Ablation on lower part of PW

Regularities of variability in the anatomical structure of the left atrium in persons of different body types

Attention of cardiac surgeons and arrhythmologists are the ostia of the pulmonary veins, which are the place of the formation of trigger points during the development of atrial fibrillation. Data on the variability of the anatomical structure of the left atrium are scarce and are often contradictory, which makes it relevant to study the variability of the structure of the left atrium in the aspect of constitutional anatomy. Purpose of the study: to establish patterns of variability in the structure of the left atrium, taking into account body type. Materials and methods: The study is based on an analysis of the results of contrast-enhanced MSCT of the heart in 105 apparently healthy individuals. Results: Analyzing the data obtained on the types of confluence of the pulmonary veins (PV) into the left atrium, it was found that in individuals of all body types, the flow of the 4-ostia pulmonary veins into the cavity of the left vertex occurs in the largest percentage of cases. Among the examined individuals, the following 7 variants of the anatomical structure of the left atrium with different frequencies of occurrence were identified: 1) typical confluence of the PV in combination with the oval shape of the orifice of the left appendage; 2) typical confluence of the PV in combination with the round shape of the mouth of the left atrium (LA) appendage; 3) confluence of the PV with a common collector on the left side in combination with the round shape of the mouth of the LA appendage; 4) confluence of the PV with a common collector on both sides in combination with the oval shape of the mouth of the LA appendage; 5) confluence of the PV with a common collector on both sides in combination with the round shape of the mouth of the LA appendage; 6) typical confluence of the PV in combination with the accessory pulmonary vein and the oval shape of the orifice of the LA appendage; 7) typical confluence of the PV in combination with the accessory pulmonary vein and the round shape of the auricle.

Connection of superior vena cava to left atrium in a newborn followed with unexplained mild cyanosis

Connection of superior vena cava to left atrium in a newborn followed with unexplained mild cyanosis

Giant Left Atrium in an Infant with Anomalous Origin of Left Coronary Artery from Pulmonary Artery

AbstractAnomalous origin of the left coronary artery (ALCAPA) from the pulmonary artery is a rare congenital anomaly with coronary steal and myocardial ischemia. The left ventricular dilatation leads to mitral regurgitation causing left atrial enlargement. We report a rare case of giant left atrium in an infant with ALCAPA-mediated secondary mitral regurgitation, which has been hitherto unreported.

Clinical usefulness of digital twin guided virtual amiodarone test in patients with atrial fibrillation ablation

It would be clinically valuable if the efficacy of antiarrhythmic drugs could be simulated in advance. We developed a digital twin to predict amiodarone efficacy in high-risk atrial fibrillation (AF) patients post-ablation. Virtual left atrium models were created from computed tomography and electroanatomical maps to simulate AF and evaluate its response to varying amiodarone concentrations. As the amiodarone concentration increased in the virtual setting, action potential duration lengthened, peak upstroke velocities decreased, and virtual AF termination became more frequent. Patients were classified into effective (those with virtually terminated AF at therapeutic doses) and ineffective groups. The one-year clinical outcomes after AF ablation showed significantly better results in the effective group compared to the ineffective group, with AF recurrence rates of 20.8% vs. 45.1% (log-rank p = 0.031, adjusted hazard ratio, 0.37 [0.14-0.98]; p = 0.046). This study highlights the potential of a digital twin-guided approach in predicting amiodarone’s effectiveness and improving personalized AF management. Clinical Trial Registration Name: The Evaluation for Prognostic Factors After Catheter Ablation of Atrial Fibrillation: Cohort Study, Registration number: NCT02138695. The date of registration: 2014-05. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02138695.

Surveillance of esophageal injury after atrial fibrillation catheter ablation.

Atrial-esophageal fistula following ablation procedures for atrial fibrillation (AF) remains a major concern. There is no standardized approach to minimize the risk and morbidity of this serious complication. The objective of this study was to present the 7-year experience of systematic endoscopic surveillance of esophageal injury after AF catheter ablation. This was a retrospective single-center registry of systematic endoscopic evaluations after consecutive AF ablation procedures performed from 2016 to 2022. A total of 677 AF ablation procedures with controlled esophagogastroduodenoscopy (EGD) were analyzed during that period. Most patients were male (71%) with paroxysmal AF (71%). Radiofrequency with electroanatomical mapping was the main ablation approach for 633 patients (93.5%). Esophageal temperature monitoring was performed using a single sensor in 220 patients (34.3%) and a multisensor probe in 296 patients (46%). Most of the patients presented no esophageal lesions (75,7%). Severe lesions (Kansas-city-classification KCC 2B) were found in 46 (6.8%) of them, requiring a new EGD in 7days. KCC2B lesions were persistent in 3 patients, 2 of whom had ulcers during healing and 1 patient with a deep ulcer of 10mm who was admitted to the hospital and underwent fasting and parenteral nutrition. The ulcer healed in the second week after the procedure. Both esophageal temperature monitoring strategies were equivalent at preventing thermal lesions. Additionally, a greater left atrium (LA) was associated with a lower incidence of esophageal ulcer (P = 0.028). Most of the lesions spontaneously healed. The incidence of esophageal injury after ablation was 24.3%. Most (72%) were mild lesions that required no therapeutic intervention. A larger left atrium (LA) was correlated with a lower incidence of thermal lesions. Early endoscopy can help diagnose severe esophageal lesions and may provide additional information for the surveillance of esophageal injury after AF ablation.

Subclinical cardiac damage monitoring in breast cancer patients treated with an anthracycline-based chemotherapy receiving left-sided breast radiation therapy: subgroup analysis from a phase 3 trial.

This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT). Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software. In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5Gy; for patients with subclinical heart damage, the mean MHD was 1.6Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage. Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events.

Persistent left superior vena cava with confluence into the left atrium: Missing contrast of the pulmonary arteries in the computed tomographic pulmonary angiography in a patient with pulmonary artery embolism

Persistent left superior vena cava with confluence into the left atrium: Missing contrast of the pulmonary arteries in the computed tomographic pulmonary angiography in a patient with pulmonary artery embolism

Assessment of left atrial function using tissue motion annular displacement in healthy dogs.

Recently, tissue motion annular displacement by speckle tracking has been shown to be a reliable method for evaluating deformation of the left atrium in healthy dogs. The aim of this study was to investigate whether tissue motion annular displacement is a feasible alternative method for studying left atrial function. One hundred healthy dogs were included. Left atrial function was assessed by tissue motion annular displacement, which was correlated to the left atrial strain and biplane area-length method-derived volumes. Left atrial reservoir function was evaluated by left atrial global tissue motion annular displacement, global left atrial strain and left atrial emptying fraction, while left atrial systolic tissue motion annular displacement and left atrial ejection fraction were used to assess left atrial systolic function. A statistically significant association between body weight and the dependent variables others than age was found. Indexed global and systolic tissue motion annular displacement decreased as body weight increased. Global iTMAD_AIIometric (mm/∛kg) showed a moderate, positive correlation with left atrial emptying fraction and with global left atrial strain. Systolic iTMAD_AIIometric (mm/∛kg) showed a moderate correlation with left atrial ejection fraction. Coefficients of variation for the intraobserver and interobserver analyses were 8.3% and 20.3% for global and 10.5% and 18.9% for systolic tissue motion annular displacement, respectively. Tissue motion annular displacement is a feasible and simple method for the evaluation of left atrial function. Our study documented the effects of body weight on left atrial tissue motion annular displacement, indicating that tissue motion annular displacement must be indexed to body weight. No influence of age or heart rate was observed on tissue motion annular displacement.

The consequences of cardiac autonomic nervous system modulation during pulmonary vein isolation: A review.

Pulmonary vein isolation (PVI) is a well-established treatment modality for atrial fibrillation (AF). Apart from the desired effect regarding the arrhythmic substrate within the left atrium, PVI commonly leads to modulation of the intrinsic cardiac autonomic nervous system (ICANS). Using the available literature, this article presents the anatomy of ICANS and describes methods of assessing its function, mainly focusing on heart rate (HR) variability metrics. Then, we summarize the modern pathophysiological outlooks on the onset and recurrence of AF and explain how the arrhythmia and the activation of ICANS are intertwined. Further, the article discusses the extent, dynamics and persistence of ICANS modulation during PVI, accounting for various modalities and procedural strategies. Both the potential benefits and pitfalls of such modulation are explored, considering AF recurrence, HR and HR variability changes, as well as the unclear effect on ventricular arrhythmias and nerve remodeling. Finally, the article aims to outline further directions of research necessary to improve our understanding of ICANS and its modulation.

Workflow of the zero‐fluoro pulsed field ablation

AbstractBackgroundZero‐fluoroscopic pulsed field ablation (PFA) is the next step in advancing pulmonary vein isolation (PVI) for atrial fibrillation (AF).MethodsA workflow incorporating a variable‐loop circular PFA catheter, intracardiac echocardiography (ICE), and a visualized sheath was applied to 15 paroxysmal AF patients.ResultsIt consisted of three steps: (1) positioning a non‐magnetic mapping catheter in the coronary sinus after creating a right atrial matrix, (2) transseptal puncture with the sheath advancement to the left atrium under ICE guidance, and (3) PFA confirming catheter‐tissue contact with tissue proximity indication.ConclusionsThis zero‐fluoro PFA workflow is feasible without advanced technique.

Are Drivers Recurring or Ephemeral? Observations from Serial Mapping of Persistent Atrial Fibrillation.

Rotational reentries and ectopic foci, or "drivers", are proposed mechanisms for persistent atrial fibrillation (persAF), but driver-based interventions have had mixed success in clinical trials. Selective targeting of drivers with multimonth stability may improve these interventions, but no prior work has investigated whether drivers can be stable on such a long timescale. We hypothesized that drivers could recur even several months after initial observation. We performed serial electrophysiology studies on paced canines (n=18, 27-35 kg) at 1-, 3-, and 6-months post-initiation of continual persAF. Using a high-density 64-electrode catheter, we captured endocardial electrograms in the left atrium (LA) and right atrium (RA) to determine the presence of drivers at each major anatomical site. We defined drivers which were repeatedly observed across consecutive studies to be recurrent. Mean probability any driver would recur was 66% (LA: 73%, RA: 41%). We also found evidence of "multirecurring" drivers, i.e., those seen in all three studies. Multirecurring drivers constituted 53% of initially observed drivers with at least one found in 92% of animals, and we found more multirecurring drivers per animal than predicted by random chance (2.6±1.5 vs. 1.2±1.1, p<0.001). Driver sites showed more enhancement than non-drivers during late gadolinium enhancement-magnetic resonance imaging (p=0.04), but we observed no relationship between enhancement and driver recurrence type. We observed recurring drivers over a 6-month period at fixed locations, confirming our hypothesis. We also found drivers to be associated with fibrosis, implying a structural basis.

The Expression of Genes CYP1A1, CYP1B1, and CYP2J3 in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.

It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions. The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a "healthy" control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats. We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes CYP1B1, CYP2J3, and CYP1A1 and in the time course of expression changes with age. We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats.

Subtle echocardiographic markers of CAD: looking beyond the LV ejection fraction in stable angina patients.

A routine echocardiogram aims at identifying only regional wall motion abnormality (RWMA) or left ventricle diastolic dysfunction (LVDD) for coronary artery disease (CAD). When absent, a study is often labeled "normal." This creates an unmet need to identify and add subtle markers of CAD to the routine echocardiogram to increase the diagnostic yield. Left ventricle (LV) systolic and diastolic parameters, along with left atrium (LA) strain parameters, were assessed using echocardiography in one hundred three patients of stable angina undergoing coronary angiography and compared with their SYNTAX score-II (SS-II). The left ventricle global longitudinal strain (LV-GLS) and LA Volume indexed (LAVi) did not correlate significantly with the SS-II. The LA filling pressures reflected by the ratio of early mitral inflow velocity with early mitral annular velocity (E/e`), however, increased significantly with SS-II, with a cut-off value >10.39 for significant CAD (pvalue <0.001). The LA reservoir function parameters, peak atrial longitudinal strain (PALS), and peak global systolic strain rate (LAsSR) decreased significantly with increasing SS-II (p values of 0.011 and 0.001, respectively). The values < 23.56 for PALS and less than 1.15 for LAsSR, showed a significant association with CAD. The LA conduit function parameter, peak global early diastolic strain rate (LAeSR), also increased significantly with increasing SS-II (p-value <0.001), with values > 1.09 having a good correlation with CAD. Besides RWMA and LV-GLS, the LV diastolic and LA strain parameters can be potential echocardiographic markers for CAD in stable angina patients.

Comparison of Cardioprotective Potential of Cannabidiol and β-Adrenergic Stimulation against Hypoxia/Reoxygenation Injury in Rat Atria and Ventricular Papillary Muscles

Background: Hypoxia is one of the most significant pathogenic factors in cardiovascular diseases. Preclinical studies suggest that nonpsychoactive cannabidiol (CBD) and β-adrenoceptor stimulation might possess cardioprotective potential against ischemia-reperfusion injury. The current study evaluates the influence of hypoxia-reoxygenation (H/R) on the function of atria and ventricular papillary muscles in the presence of CBD and the nonselective β-adrenoceptor agonist isoprenaline (ISO). Methods: The concentration curves for ISO were constructed in the presence of CBD (1 µM) before or after H/R. In chronic experiments (CBD 10 mg/kg, 14 days), the left atria isolated from spontaneously hypertensive (SHR) and their normotensive control (WKY) rats were subjected to H/R following ISO administration. Results: Hypoxia decreased the rate and force of contractions in all compartments. The right atria were the most resistant to hypoxia regardless of prior β-adrenergic stimulation. Previous β-adrenergic stimulation improved recovery in isolated left atria and right (but not left) papillary muscles. Acute (but not chronic) CBD administration increased the effects of ISO in left atria and right (but not left) papillary muscles. Hypertension accelerates left atrial recovery during reoxygenation. Conclusion: H/R directly modifies the function of particular cardiac compartments in a manner dependent on cardiac region and β-adrenergic prestimulation. The moderate direct cardioprotective potential of CBD and β-adrenergic stimulation against H/R is dependent on the cardiac region, and it is less than in the whole heart with preserved coronary flow. In clinical terms, our research expands the existing knowledge about the impact of cannabidiol on cardiac ischemia, the world′s leading cause of death.

Distinct methylome profile of cfDNA in AMI patients reveals significant alteration in cAMP signaling pathway genes regulating cardiac muscle contraction

BackgroundThe role of epigenetics in cardiovascular diseases has paved the way for innovative therapeutic approaches. Investigating epigenetic changes using cell-free DNA (cfDNA) holds substantial promise beyond mere diagnostics, especially for heart-related conditions like acute myocardial infarction (AMI), where obtaining tissue samples is a challenge. This study explores the methylation patterns of cfDNA in AMI patients and compares them with genomic DNA (gDNA) from the same individuals, aiming to evaluate the effectiveness of cfDNA as a valuable resource for studying heart-related diseases.MethodologyWe generated global methylome profiles of cfDNA and gDNA from 25 AMI patients using EM-Seq. Tissue deconvolution analysis was performed to estimate tissue specificity based on the methylation patterns. Differentially methylated loci were identified and explored to understand AMI pathophysiology.ResultsComparative analysis of cfDNA and gDNA methylation patterns in AMI patients reveals cfDNA holds more significance than gDNA. Principal component analysis revealed distinct clusters for cfDNA and gDNA, indicating distinct methylome profiles. cfDNA originated from multiple sources, predominantly from neutrophils (~ 75%) and about 10% from the left atrium, highlighting cardiac-specific changes. In contrast, immune cells are the major source of gDNA, indicative of inflammatory responses. Gene set enrichment analysis (GSEA) associates cfDNA methylation patterns with pathways related to cardiac muscle contraction, inflammation, hypoxia, and lipid metabolism. The affected genes include G protein-coupled receptors (GHSR, FFAR2, HTR1A, and VIPR2) that are part of the cAMP signaling pathway.ConclusionEpigenetic changes in cfDNA are more specific to cardiac tissue compared to those in gDNA, providing better insights into the molecular mechanisms involved in AMI. Genes that are differentially methylated in cfDNA and regulate core pathways, such as cAMP signaling, could be targeted for clinical applications, including the development of effective biomarkers and therapeutic targets.

Right-to-left-shunts in patients scheduled for neurosurgical intervention in semi-sitting position – a literature review based on two case scenarios

BackgroundNeurosurgery performed in the semi-sitting position provides advantages for certain procedures. However, this approach is associated with potential complications, particularly venous air embolism. Due to typically negative venous pressure at the wound site, air can be drawn into the veins. This risk is especially high in patients presenting with an intra- or extracardiac right-to-left-shunt. Transoesophageal echocardiography can be used to detect a patent foramen ovale or other possible pulmonary-systemic shunt before placing the patient in the sitting position.Case presentationIn this report, we present two young patients undergoing scheduled microsurgical vestibular schwannoma removal in a semi-sitting position who were diagnosed with congenital heart defects during routine perioperative assessment to detect possible intracardiac right-to-left shunts, using pre- and intraoperative transesophageal echocardiography (TEE) and additionally conducting an agitated saline bubble study under Valsalva manoeuvre. Patient A was diagnosed with a persistent left superior vena cava and Patient B with an unroofed coronary sinus (UCS). These findings confronted the anesthesiological and surgical teams with difficult individual decisions regarding further perioperative management.ConclusionsPerioperative transesophageal echocardiography is a diagnostic tool to both detect intraoperative position-related air embolisms and to rule out intracardiac right-to-left shunts, e.g. a patent foramen ovale, in order to decide for or against a (semi-)sitting position. Depending on the surgical circumstances a semi-sitting positioning of patients presenting with an intracardiac right-to-left-shunt, e.g. a PFO, can be feasible in individual cases if there is an implemented therapeutic algorithm to immediately terminate significant venous air entry. However, since certain other intra- or extracardiac right-to-left-shunts, such as here presented PLSVC or UCS, are rare, there is no definitive way of estimating the amount of entered air through detected shunts or anomalous vessels. Therefore, it is recommended to avoid a (semi-)sitting position in favour of a lateral or prone position for a patient undergoing intracranial surgery, once the perioperative TEE shows air bubbles in the left atrium or ventricle whose origins cannot be defined solely through TEE for certain in order to ensure patient safety by minimizing the risk of intraoperative paradoxical air embolisms.