Comparison of the early cardiac electromechanical remodeling following transcatheter and surgical secundum atrial septal defect closure in adults

Background Secundum atrial septal defect (ASD) closure leads to electrical and mechanical remodeling that occurs early after shunt disappearance. The relationship between electromechanical remodeling using electrocardiogram (ECG) and cardiac magnetic resonance (CMR) after percutaneous and surgical closure has not yet been recorded in prospective studies. Objective We thought to study right atrium (RA) and right ventricle (RV) changes by CMR 3 months after transcatheter and surgical closure and their comparison with electrical remodeling by ECG. Results We prospectively evaluated 30 consecutive adult patients with isolated secundum ASD who were referred for (transcatheter and surgical) ASD closure. There was significant reduction in all of the electrical parameters within the same group as compared to the baseline values, except P wave dispersion (Pd). (P max was 97.33 ± 16.67 (pre closure) to 76 ± 15.49 (post closure) in the device group and 97.33 ± 12.79 (preclosure) to 73.33 ± 16.32 (post closure) in the surgical group, QRS complex was 104 ± 18.82 (preclosure) to 80 ± 18.51 (post closure) in the device group and 106.67 ± 14.47 (preclosure) to 86.67 ± 17.99 (post closure) in the surgical group. QTc maximum was 478.53 ± 36.79 (preclosure) to 412.53 ± 38.03 (post closure) in the device group and 470.53 ± 65.70 (preclosure) to 405.93 ± 63.08 (post closure) in the surgical group, and QTc dispersion was 70.33 ± 24.04 (preclosure) to 60.26 ± 28.56 (post closure) in the device group and 80.73 ± 30.38 (preclosure) to 60.27 ± 28.57 (post closure) in the surgical group).There was no significant difference between two groups indicating that transcatheter and surgical closure had led to equivalent value of electrical remodeling. In CMR study, we measured RA maximal volume and right ventricle end diastolic volume (RVEDV), RA maximal volume decreased significantly as compared to the base line values post closure in both groups (P value < 0.001). The reduction in RA max volume was more in the transcatheter closure group; however, this difference was not statistically significant when compared with the surgical arm (P value = 0.5).RVEDV decreased significantly in both groups as compared to the baseline values (P value < 0.001). Transcatheter closure resulted in more significant reduction in the RVEDV than the surgical closure (P value = 0.03). Conclusion Our study showed early significant electromechanical reverse remodeling in most of the study parameters from the baseline values after ASD closure. We found no significant differences in all of the electrical and RA mechanical remodeling parameters with significantly better mechanical remodeling of RV in the device group.

Decoding electrocardiographic predictors of left ventricular mechanical remodeling in patients with left bundle branch block

Introduction – Left bundle branch block (LBBB) occurrence is uncommon in the general population (~1-3%), but is more prevalent among patients with congestive heart failure (~30%), and portends worse prognosis1-3. The impact of LBBB on left ventricular (LV) systolic function can range from minimal to dramatic reduction of ejection fraction. The delay in electrical activation subsequently triggers dyssynchronous contraction of the LV opposing walls, leading to ventricular remodeling and elevated LV filling pressures. This is turn results in electrical and mechanical left atrium (LA) remodeling. The left ventricular activation time (LVAT) and P-wave terminal force in lead V1 (PTFV1) have been correlated with cardiac resynchronization response. However, the relationship between these electrocardiographic markers and LV mechanical remodeling has not been evaluated. Aims – The aim of this study is to investigate the relationship between LVAT and PTFV1 recorded on ECG and the LV mechanical remodeling evaluated by the left ventricular end-diastolic diameter (LVEDd) in patients with LBBB. Methods – We have conducted a retrospective, observational study on 155 consecutive patients diagnosed with LBBB admitted in our clinic between January 2017 and December 2019 with NYHA class I-IV, regardless of the left ventricle ejection fraction (LVEF). Biventricular electrical activation in LBBB was performed by measuring the right and left ventricular activation times (RVAT, LVAT) and electrical activation of the LA was analyzed by measuring P-wave terminal force in lead V1 (PTFV1). Results – In our cohort, LVEDd is statistically significantly correlated with LVAT and PTFV1, with a higher Pearson correlation coefficient for LVAT compared to PTFV1. In multivariate analysis LVAT and PTFV1 are independent predictors of LVEDd. Conclusion – This study suggests that LV mechanical remodeling in patients with LBBB can be predicted by the delayed electrical activation of the LV and the magnitude of P-wave negative terminal forces in V1.

Bachmann bundle impairment following linear ablation of left anterior wall: impact on left atrial function

Background: We aimed to evaluate the effect of Bachmann bundle (BB) impairment on electrical and mechanical function of the left atrium (LA), as well as the long-term clinical impact of such impairment. Design: We measured activation time in the five LA walls in 56 patients with atrial fibrillation. LA reservoir, conduit, and contractile function were also evaluated. Patients were divided into two groups based on ablation strategy: the circumferential pulmonary vein isolation (CPVI) group and CPVI with anterior wall linear ablation (LAWA) group. Patients in the CPVI+LAWA group were divided into two sub-groups based on ECG differences following ablation: the BB impairment group and intact BB group. LA activation time and function were then compared between the ablation strategy groups and the CPVI+LAWA subgroups. Results: Patients in the CPVI+LAWA group exhibited longer activation times in the anterior and lateral walls of the LA, poorer LA synchrony, and reduced LA contractile and reservoir function when compared with those in the CPVI group. In the BB impairment subgroup, we observed a discrepancy between electrical/mechanical remodeling. Among five walls, activation time was longest in this region. BB impairment was also associated with reduced LA function. Conclusion: Significant changes in LA function and conductibility were observed in patients with anterior wall ablation, especially those with iatrogenic BB impairment.

Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin

Chronic inflammation and subsequent tissue fibrosis are associated with a biochemical and mechanical remodeling of the fibronectin matrix. Due to its conformational lability, fibronectin is considerably stretched by the contractile forces of the fibrotic microenvironment, resulting in the unfolding of its Type III domains. In earlier studies, we have shown that a peptide mimetic of a partially unfolded fibronectin Type III domain, FnIII-1c, functions as a Damage Associated Molecular Pattern (DAMP) molecule to induce activation of a toll-like receptor 4 (TLR4)/NF-κB pathway and the subsequent release of fibro-inflammatory cytokines from human dermal fibroblasts. In the current study, we evaluated the requirement of the canonical TLR4/MD2/CD14 receptor complex in the regulation of FnIII-1c induced cytokine release. Using dermal fibroblasts and human embryonic kidney (HEK) cells, we found that all the components of the TLR4/MD2/CD14 complex were required for the release of the fibro-inflammatory cytokine, interleukin 8 (IL-8) in response to both FnIII-1c and the canonical TLR4 ligand, lipopolysaccharide (LPS). However, FnIII-1c mediated IL-8 release was strictly dependent on membrane-associated CD14, while LPS could use soluble CD14. These findings demonstrate that LPS and FnIII-1c share a similar but not identical mechanism of TLR4 activation in human dermal fibroblasts.

Structural and mechanical remodeling of the cytoskeleton maintains tensional homeostasis in 3D microtissues under acute dynamic stretch

When stretched, cells cultured on 2D substrates share a universal softening and fluidization response that arises from poorly understood remodeling of well-conserved cytoskeletal elements. It is known, however, that the structure and distribution of the cytoskeleton is profoundly influenced by the dimensionality of a cell’s environment. Therefore, in this study we aimed to determine whether cells cultured in a 3D matrix share this softening behavior and to link it to cytoskeletal remodeling. To achieve this, we developed a high-throughput approach to measure the dynamic mechanical properties of cells and allow for sub-cellular imaging within physiologically relevant 3D microtissues. We found that fibroblast, smooth muscle and skeletal muscle microtissues strain softened but did not fluidize, and upon loading cessation, they regained their initial mechanical properties. Furthermore, microtissue prestress decreased with the strain amplitude to maintain a constant mean tension. This adaptation under an auxotonic condition resulted in lengthening. A filamentous actin cytoskeleton was required, and responses were mirrored by changes to actin remodeling rates and visual evidence of stretch-induced actin depolymerization. Our new approach for assessing cell mechanics has linked behaviors seen in 2D cultures to a 3D matrix, and connected remodeling of the cytoskeleton to homeostatic mechanical regulation of tissues.