In vitro characterization of radiofrequency ablation lesions in equine and swine myocardial tissue.

Radiofrequency ablation is a promising technique for arrhythmia treatment in horses. Due to the thicker myocardial wall and higher blood flow in horses, it is unknown if conventional radiofrequency settings used in human medicine can be extrapolated to horses. The study aim is to describe the effect of ablation settings on lesion dimensions in equine myocardium. To study species dependent effects, results were compared to swine myocardium. Right ventricular and right and left atrial equine myocardium and right ventricular swine myocardium were suspended in a bath with circulating isotonic saline at 37 °C. The ablation catheter delivered radiofrequency energy at different-power-duration combinations with a contact force of 20 g. Lesion depth and width were measured and lesion volume was calculated. Higher power or longer duration of radiofrequency energy delivery increased lesion size significantly in the equine atrial myocardium and in equine and swine ventricular myocardium (P < 0.001). Mean lesion depth in equine atrial myocardium ranged from 2.9 to 5.5 mm with a diameter ranging from 6.9 to 10.1 mm. Lesion diameter was significantly larger in equine tissue compared to swine tissue (P = 0.020). Obtained data in combination with estimated wall thickness can improve lesion transmurality which might reduce arrhythmia recurrence. Optimal ablation settings may differ between species.

Predictive value of the left atrioventricular coupling index for recurrence after radiofrequency ablation of paroxysmal atrial fibrillation.

BACKGROUND: Although patients with paroxysmal atrial fibrillation (PAF) are preferred to undergo catheter ablation (CA), the high possibility of recurrence following surgery is still concerning. We aimed to evaluate the ability of the left atrioventricular coupling index (LACI), which is the ratio of the left atrium end-diastolic volume to the left ventricle end-diastolic volume, to predict PAF recurrence after CA. METHODS: Patients with PAF undergoing CA for the first time between January 2018 and June 2021 were admitted and grouped by recurrence within a year. LACI was measured before CA using ultrasonography. Risk factors identified by multivariable logistic regression analysis, and the area under the receiver operating characteristic (ROC) curve was used to assess the ability of LACI to predict PAF recurrence after CAP. RESULTS: Among the 204 patients treated at our hospital, 164 patients were included in the research after eliminating those who were lost to follow-up. Among them, 56 individuals had recurrence following a 90-day blanking period. Recurrence is more likely in elderly patients with high blood pressure. Patients who suffered recurrence exhibited lower left atrial ejection fraction and increased LACI, left atrial volume minimum, and left atrium volume index maximum. LACI was an independent risk factor for postoperative recurrence (OR: 1.526, 95% CI: 1.325-1.757, P < 0.001), and ROC displayed remarkable predictive value [area under the curve (AUC) = 0.868]. CONCLUSIONS: High LACI is significantly associated with postoperative recurrence in PAF patients, and LACI has incremental prognostic value to predict recurrence.

Relationship between left atrial isolated surface area and early-term recurrence in patients with persistent atrial fibrillation after cryoballoon ablation.

OBJECTIVE: To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. METHODS: 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. RESULTS: 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0-0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256-25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. CONCLUSION: A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.

A scenario for heart failure during the filling phase.

Heart failure (HF) is a life-threating cardiac disease that develops progressively for the reduced ability of the left ventricle (LV) to pump blood into the circulation during systole. HF can also develop in patients with a preserved systolic function, typically in presence of hypertrophic cardiomyopathy (HCM). This type of HF is sometimes termed as diastolic HF, but its biomechanical origin is still unclear. This study employs a physics-based analysis of both the LV and left atrium (LA) in selected HCM patients and matched healthy subjects using 3D echocardiography and demonstrates that alteration on the LV side (stiffening) reduces the elastic recovery of the LA. Moreover, the analysis of the forces exchanged between the two chambers demonstrates that they result unbalanced, keeping the LA in a sustained stretched condition that leads to dilation. This scenario clarifies the diastolic root of the dysfunction that may likely be the cause of the spiraling of events progressing toward failure of both LA emptying and LV filling. This deeply interdisciplinary study provides a physics-based basis for both physics/engineering modeling of heart function and to cardiologists for the design of clinical studies.

Subclinical impairment of the left atrium is associated with MRI-based lung volume but not with parameters from pulmonary function testing.

Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm2, while maximal and minimal LA size from gated measurements were 19.6 cm2 and 11.9 cm2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = - 0.03, p = 0.006; ß = - 0.03, p = 0.021; ß = - 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT.

In vivo cardiovascular profile of ryanodine receptor 2 inhibitor M201-A: Utility as an anti-atrial fibrillatory drug for patients suffering from heart failure with preserved ejection fraction.

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) often coexist; however, clinically available anti-AF drugs can exacerbate symptoms of HFpEF. M201-A suppressed ryanodine receptor-mediated diastolic Ca2+ leakage, possibly inhibiting common pathological processes toward AF and HFpEF. To bridge the basic information to clinical practice, we assessed its cardiohemodynamic, anti-AF and ventricular proarrhythmic profile using halothane-anesthetized dogs (n = 4). M201-A hydrochloride in doses of 0.03, 0.3 and 3 mg/kg/10 min was intravenously administered, providing peak plasma concentrations of 0.09, 0.81 and 5.70 µg/mL, respectively. The high dose of M201-A showed various cardiovascular actions. Namely, M201-A increased mean blood pressure and tended to enhance isovolumetric ventricular relaxation without suppressing ventricular contraction or decreasing cardiac output. M201-A enhanced atrioventricular conduction, but hardy affected intra-atrial/ventricular conduction. Importantly, M201-A prolonged effective refractory period more potently in the atrium than in the ventricle, indicating that it may become an atrial-selective antiarrhythmic drug. Meanwhile, M201-A prolonged QT interval/QTcV, and showed reverse frequency-dependent delay of ventricular repolarization. M201-A prolonged J-Tpeakc without prolonging Tpeak-Tend or terminal repolarization period, indicating the risk of causing torsade de pointes is negligible. Thus, M201-A is expected to become a hopeful therapeutic strategy for patients having pathology of both AF and HFpEF.

Atrial Adaptations in Athletes Heart.

BACKGROUND: Intensive training efforts are associated with hemodynamic changes accompanied by increases in cardiac output and stroke volume related to higher peak oxygen consumption and better athletic performance during exercise. These hemodynamic changes induce an enlargement of cardiac chambers, but also of the atria and may result in an athletes' heart (AH). Data from large studies about atrial enlargement in AH are sparse. METHODS: Competitive athletes aged ≥18 years, who presented for pre-participation screening 04/2020-10/2021 were included in this study and stratified for AH (defined as physiologically increased heart volume >13.0 in males and >12.0 mL/kg in females). RESULTS: Overall, 646 athletes aged ≥18 years (median age 24.0 [20.0/31.0] years; 206 [31.9%] females) were included in our study 04/2020-10/2021; among these, 118 (18.3%) had an AH. The computed absolute heart volume was 969.4 (853.1/1083.0) mL in athletes with AH and 841.3 (707.4/966.3) mL in those without AH (p < 0.001). AH was associated with larger left ventricular mass (206.6 ± 39.0 vs. 182.7 ± 44.2 g, p < 0.001). LA area (15.4 [13.7/18.2] vs. 14.3 [12.0/16.3] cm2, p < 0.001) and RA area (15.8 [13.8/18.6] vs. 14.5 [12.3/17.0] cm2, p < 0.001) were enlarged in AH versus those athletes without AH. The logistic regressions confirmed an independent association of AH on LV mass (OR 1.05 [95% CI 1.04-1.06], p < 0.001). LA area (OR 1.29 [95% CI 1.19-1.39], p < 0.001) as well as RA area (OR 1.28 [95% CI 1.19-1.38], p < 0.001) were afflicted by AH. CONCLUSION: An AH is accompanied by significant enlargement of the atria as well as increased cardiac muscle mass.

MCPIP1 promotes atrial remodeling by exacerbating miR-26a-5p/FRAT/Wnt axis-mediated atrial fibrosis in a rat model susceptible to atrial fibrillation.

Atrial fibrosis plays a critical role in the pathogenesis of atrial fibrillation (AF). Monocyte chemotactic protein-induced protein-1 (MCPIP1), recognized as a functional ribonuclease (RNase), exacerbates cardiac remodeling and contributes to a range of cardiovascular diseases. However, the involvement of MCPIP1 in atrial fibrosis and development of AF, along with its underlying biological mechanisms, remains poorly understood. This study demonstrated that knockdown of MCPIP1 significantly reduced AF inducibility, decreased left atrial diameter, and ameliorated atrial fibrosis, coinciding with reduced FRAT1/2/Wnt/ß-catenin signaling. Furthermore, the MCPIP1-D141N mutation attenuated AF vulnerability and atrial remodeling compared to MCPIP1 overexpression in an acetylcholine and calcium chloride (ACh-CaCl2)-induced rat model of AF. Conversely, overexpression of FRAT1/2 partially reversed the cardioprotective effects of MCPIP1-D141N mutation. Using H9C2 cell lines, we observed that MCPIP1 may induce a transcriptional effect that downregulates miR-26a-5p expression, and luciferase and RNA immunoprecipitation (RIP) assays substantiated the direct interaction between miR-26a-5p and FRAT1/2. Moreover, overexpression of miR-26a-5p countered MCPIP1-induced atrial remodeling and attenuated the progression of AF. In conclusion, these findings indicate that MCPIP1 facilitates atrial remodeling and the progression of AF by exacerbating miR-26a-5p/FRAT/Wnt axis-mediated atrial fibrosis through its RNase activity in an ACh-CaCl2-induced rat model of AF.

The value of computed tomography angiography for evaluation of left atrial enlargement in patients with persistent atrial fibrillation.

BACKGROUND: The post-processing technology of CTA offers significant advantages in evaluating left atrial enlargement (LAE) in patients with persistent atrial fibrillation (PAF). This study aims to identify parameters for rapidly and accurately diagnosing LAE in patients with PAF using CT cross-sections. METHODS: Left atrial pulmonary venous (PV) CT was performed to 300 PAF patients with dual-source CT, and left atrial volume (LAV), left atrial anteroposterior diameter (LAD1), left atrial transverse diameter (LAD2), and left atrial area (LAA) were measured in the ventricular end systolic (ES) and middle diastolic (MD). LA index (LAI) = LA parameter/body surface area (BSA). Left atrial volume index (LAVIES) > 77.7 ml/m2 was used as the reference standard for the LAE diagnosis. RESULTS: 227 patients were enrolled in the group, 101 (44.5%) of whom had LAE. LAVES and LAVMD (r = 0.983), LAVIES and LAVIMD (r = 0.984), LAAES and LAVIES (r = 0.817), LAAMD and LAVIES (r = 0.814) had strong positive correlations. The area under curve (AUC) showed that all measured parameters were suitable for diagnosing LAE, and the diagnostic efficacy was compared as follows: LAA/LAAI> LAD> the relative value index of LAD, LAD2> LAD1. LAA and LAAI demonstrated comparable diagnostic efficacy, with LAA being more readily available than LAAI. CONCLUSIONS: The axial LAA measured by CTA can be served as a parameter for the rapid and accurate diagnosis of LAE in patients with PAF.

Adjuncts to annuloplasty in atrial functional mitral regurgitation.

Atrial fibrillation is the most common cardiac arrhythmia, leading to progressive dilation of cardiac chambers, abnormal contraction patterns of the atria and ventricles and, potentially, atrioventricular valvular insufficiency. Moreover, heart failure with preserved ejection fraction is often present and closely intertwined with disease initiation and progression. Surgical valve repair with a true-sized ring annuloplasty is a well-established treatment option in atrial functional mitral regurgitation. While early results are good, recent studies have brought the durability of this repair approach into question, highlighting the need for further refinement of the surgical strategy. In particular, repair strategies that simultaneously target the mitral valve as well as the left ventricle could provide improved repair durability.

Aldosterone Robustly Promotes Atrial Fibrillation in the Presence of Chronic Volume Overload in Rats.

We investigated the modulatory effects of aldosterone on atrial remodeling induced by an abdominal aorto-venocaval shunt (AVS) in rats, as patients with primary hyperaldosteronism are suggested to have a higher risk of developing atrial fibrillation (AF). The rats were divided into four groups based on the basis of whether they underwent AVS surgery, received aldosterone using an intraperitoneally implanted osmotic minipump, or both. Aldosterone was started at 0.5 µg/h during the AVS surgery, and morphological and electrophysiological assessments were performed four weeks after AVS creation. The atrial structural changes induced by AVS, including atrial cell hypertrophy and fibrosis, were not modulated by aldosterone, whereas P-wave duration was longer in aldosterone-treated AVS rats than in non-treated rats. Although the average AF duration induced by burst pacing was 10-25 s in the untreated, aldosterone-treated, and AVS rats, the AF duration was approximately 100 s in the aldosterone-treated AVS rats. Meanwhile, there was no significant difference in the atrial effective refractory period among the four experimental groups. Notably, premature atrial contractions (PAC) were frequently observed in aldosterone-treated sham rats, while paroxysmal AF, in addition to PAC, was detected in aldosterone-treated AVS rats, which was not induced in non-treated AVS rats. These findings suggest that aldosterone robustly promotes AF, particularly in the presence of chronic volume overload.

Pathways to precision medicine: deciphering the secrets of physiological and pathological atrial enlargement.

Cardiac functional, morphological, and histological analysis, coupled with liquid chromatography and mass spectrometry, of two transgenic mouse models with cardiomyocyte-specific overexpression of insulin-like growth factor 1 receptor (IGF1R) or a dominant-negative PI3K mutant (DCM-dnPI3K) revealed distinctive functional and molecular profiles during physiological (driven by IGF1R overexpression) and pathological (driven by dn-PI3K overexpression) atrial remodeling. The current study confirmed previously reported findings, including ventricular dilatation and enhanced systolic function with no evidence of arrhythmia in IGF1R model, as well as ventricular hypertrophy and decreased systolic function with intermittent atrial fibrillation in DCM-dnPI3K model. Novel findings obtained from the left atrial (LA) characterization of female mice revealed that physiological atrial enlargement resulted from increased atrial myocyte size and was associated with preserved atrial function, as determined by maintained LA ejection fraction (EF). The proteomic profile of IGF1R transgenic (Tg) mice was enriched for metabolic remodeling and showed a protein expression pattern similar to that of healthy human atria; on the other hand, pathological atrial enlargement resulted from increased atrial fibrosis with normal myocyte size and was associated with impaired atrial function due to a reduced LA EF. The proteomic profile of DCM-dnPI3K mice was enriched to both metabolic and structural remodeling and showed a protein expression pattern similar to that of human AF atria.

The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes.

BACKGROUND: Doxorubicin is an important anticancer drug, however, elicits dose-dependently cardiomyopathy. Given its mode of action, i.e. topoisomerase inhibition and DNA damage, we investigated genetic events associated with cardiomyopathy and searched for mechanism-based possibilities to alleviate cardiotoxicity. We treated rats at clinically relevant doses of doxorubicin. Histopathology and transmission electron microscopy (TEM) defined cardiac lesions, and transcriptomics unveiled cardiomyopathy-associated gene regulations. Genomic-footprints revealed critical components of Abl1-p53-signaling, and EMSA-assays evidenced Abl1 DNA-binding activity. Gene reporter assays confirmed Abl1 activity on p53-targets while immunohistochemistry/immunofluorescence microscopy demonstrated Abl1, p53&p73 signaling. RESULTS: Doxorubicin treatment caused dose-dependently toxic cardiomyopathy, and TEM evidenced damaged mitochondria and myofibrillar disarray. Surviving cardiomyocytes repressed Parkin-1 and Bnip3-mediated mitophagy, stimulated dynamin-1-like dependent mitochondrial fission and induced anti-apoptotic Bag1 signaling. Thus, we observed induced mitochondrial biogenesis. Transcriptomics discovered heterogeneity in cellular responses with minimal overlap between treatments, and the data are highly suggestive for distinct cardiomyocyte (sub)populations which differed in their resilience and reparative capacity. Genome-wide footprints revealed Abl1 and p53 enriched binding sites in doxorubicin-regulated genes, and we confirmed Abl1 DNA-binding activity in EMSA-assays. Extraordinarily, Abl1 signaling differed in the heart with highly significant regulations of Abl1, p53 and p73 in atrial cardiomyocytes. Conversely, in ventricular cardiomyocytes, Abl1 solely-modulated p53-signaling that was BAX transcription-independent. Gene reporter assays established Abl1 cofactor activity for the p53-reporter PG13-luc, and ectopic Abl1 expression stimulated p53-mediated apoptosis. CONCLUSIONS: The tyrosine kinase Abl1 is of critical importance in doxorubicin induced cardiomyopathy, and we propose its inhibition as means to diminish risk of cardiotoxicity.

Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.

Single-chamber atrial pacing†+†Micra AV implantation: A case report.

RATIONALE: The use of transvenous pacing leads is associated with the risk of tricuspid valve dysfunction, mainly due to the continuous presence of the leads can have an impact on subsequent tricuspid function and possible operation injury of the tricuspid valve during implantation or operation. PATIENT CONCERNS: A 69-year-old female with a history of syncope for 9 months was admitted to the hospital. The electrocardiogram showed sinus bradycardia, junctional escape rhythm, and a heart rate of 44 bpm. Echocardiography suggested a downward displacement and severe insufficiency of the tricuspid valve and atrial septal defect. DIAGNOSES: The cause of syncope was considered to be sick sinus syndrome. The patient was diagnosed with Ebstein anomaly and is considered a candidate for surgical intervention. INTERVENTIONS: To avoid aggravating tricuspid insufficiency by pacing leads crossing the tricuspid valve and hindering subsequent tricuspid valve surgery, a single-chamber pacing mode with atrial pacing (AAI) lead and Micra AV was chosen for maintaining atrioventricular synchrony after multidisciplinary discussion. OUTCOMES: The patient had stable parameters and was in good general condition at 1- and 3-month outpatient follow-ups after discharge. LESSONS: This is the first case of new implantation of single-chamber atrial pacing + leadless ventricular pacing with Micra AV, an alternative strategy to epicardial or coronary sinus system for tricuspid valve displacement and severe tricuspid regurgitation.

BMP2 Diminishes Angiotensin II-Induced Atrial Fibrillation by Inhibiting NLRP3 Inflammasome Signaling in Atrial Fibroblasts.

Atrial fibrillation (AF) is the most common sustained arrhythmia to affect 1% of the global population and increases with age. Atrial fibrosis is a crucial substrate for promoting structural remodeling to cause atrial arrhythmogenesis. Bone morphogenic protein 2 (BMP2) has been reported to be involved in cardiac fibrogenesis. However, its role in modulating atrial fibrosis to affect AF development remains unknown. Our study aimed to investigate the expression of BMP2 under different AF conditions and the effect of BMP2 on the progression of atrial fibrosis using an angiotensin II (Ang II) rat model and an ex vivo cardiac fibroblast model. The qRT-PCR and Western blot assay showed increased BMP2 mRNA and protein levels in the atria of chronic AF patients and the right atria of a tachypacing rabbit model. In contrast, the levels of BMP2 receptor mRNA were comparable. The AF incidence of the Ang II rat was higher than that of a control rat, which was reduced by BMP2 treatment. Masson staining demonstrated an anti-fibrogenic impact on BMP2-subjected rat atria compared to only Ang II-treated rat atria. RNA-sequencing indicated the potential function of blocking NLRP3-associted inflammasome activation in BMP2-treated rat atrial tissues. In vitro, transfecting BMP2 shRNA into neonatal rat atrial fibroblasts upregulated the mRNA levels of NLRP3/Caspase-1/p20/ASC and the secretion of IL-1ß and IL-6. In contrast, recombinant BMP2 protein attenuated the increased levels of the NLRP3 inflammasome pathway induced by Ang II. In summary, BMP2 opposes atrial fibrosis to alleviate AF susceptibility by inhibiting the activation of the inflammasome in atrial fibroblasts.

Right Ventricular Myxoma with a Papillary Muscular Origin.

Cardiac myxomas in the right ventricle are a very rare condition. In this case report, we describe an exceptionally uncommon case involving a right ventricular cardiac myxoma, originating from a papillary muscle, extending to both the tricuspid valve and the right atrium. The valve was able to be repaired via artificial chorda implantation.