Background-Simple conceptual ideas about cardiac resynchronization therapy assume that biventricular (BiV) pacing results in collision of right and left ventricular (LV) pacing-derived wavefronts. However, this concept is contradicted by the minor reduction in QRS duration usually observed. We investigated the electric mechanisms of cardiac resynchronization therapy by performing detailed electric mapping during extensive pacing protocols in dyssynchronous canine hearts. Methods and Results-Studies were performed in anesthetized dogs with acute left bundle-branch block (LBBB, n=10) and chronic LBBB with tachypacing-induced heart failure (LBBB+HF, n=6). Activation times (AT) were measured using LV endocardial contact and noncontact mapping and epicardial contact mapping. BiV pacing reduced QRS duration by 21±10% in LBBB but only by 5±12% in LBBB+HF hearts. Transseptal impulse conduction was significantly slower in LBBB+HF than in LBBB hearts (67±9 versus 44±16 ms, respectively), and in both groups significantly slower than transmural LV conduction (≈30 ms). In both groups QRS duration and vector and the epicardial AT vector amplitude and angle were significantly different between LV and BiV pacing, whereas the endocardial AT vector was similar. During variation of atrioventricular delay while LV pacing, and ventriculo-ventricular delay while BiV pacing, the optimal hemodynamic effect was achieved when epicardial AT and QRS vectors were minimal and endocardial AT vector indicated LV preexcitation. Conclusions-Due

Background-The relative contribution of electromechanical synchronization and ventricular filling to the optimal hemodynamic effect in cardiac resynchronization therapy (CRT) during adjustment of stimulation-timings is incompletely understood. We investigated whether optimal hemodynamic effect in CRT requires collision of pacing-induced and intrinsic activation waves and optimal filling of the left ventricle (LV). Methods and Results-CRT was performed in dogs with chronic left bundle-branch block (n=8) or atrioventricular (AV) block (n=6) through atrial (A), right ventricular (RV) apex, and LV-basolateral pacing. A 100 randomized combinations of A-LV/A-RV intervals were tested. Total activation time (TAT) was calculated from >100 contact mapping electrodes. Mechanical interventricular dyssynchrony was determined as the time delay between upslopes of LV and RV pressure curves. Settings providing an increase in LVdP/dt max (maximal rate of rise of left ventricular pressure) of ≥90% of the maximum LVdP/dt max value were defined as optimal (CRT opt ). Filling was assessed by changes in LV end-diastolic volume (EDV; conductance catheter technique). In all hearts, CRT opt was observed during multiple settings, providing an average LVdP/dt max increase of ≈15%. In AV-block hearts, CRT opt exclusively depended on interventricular-interval and not on AVinterval. In left bundle-branch block hearts, CRT opt occurred at A-LV intervals that allowed fusion of LV-pacing-derived activation with right bundle-derived activation. In all animals, CRT opt occurred at settings resulting in the largest decrease in TAT and mechanical interventricular dyssynchrony, whereas LV EDV hardly changed. Conclusions-In left bundle-branch block and AV-block hearts, optimal hemodynamic effect of CRT depends on optimal interplay between pacing-induced and intrinsic activation waves and the corresponding mechanical resynchronization rather than filling.

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Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT.Electronic supplementary materialThe online version of this article (doi:10.1007/s12265-011-9336-5) contains supplementary material, which is available to authorized users.

AimsLeft bundle branch block (LBBB) creates considerable regional differences in mechanical load within the left ventricle (LV). We investigated expression of selected microRNAs (miRs) in relation to regional hypertrophy and fibrosis in LBBB hearts and their reversibility upon cardiac resynchronization therapy (CRT).Methods and resultsEighteen dogs were followed for 4 months after induction of LBBB, 10 of which received CRT after 2 months. Five additional dogs served as control. LV geometric changes were determined by echocardiography and myocardial strain by magnetic resonance imaging tagging. Expression levels of miRs, their target genes: connective tissue growth factor (CTGF), serum response factor (SRF), nuclear factor of activated T cells (NFATc4), and cardiomyocyte diameter and collagen deposition were measured in the septum and LV free wall (LVfw). In LBBB hearts, LVfw and septal systolic circumferential strain were 200% and 50% of control, respectively. This coincided with local hypertrophy in the LVfw. MiR‐133a expression was reduced by 33% in the LVfw, which corresponded with a selective increase of CTGF expression in the LVfw (279% of control). By contrast, no change was observed in SRF and NFATc4 expression was decreased in LBBB hearts. CRT normalized strain patterns and reversed miR‐133a and CTGF expression towards normal, expression of other miRs, related to remodelling, such as miR‐199b and miR‐155f, were not affected.ConclusionsIn the clinically relevant large animal model of LBBB, a close inverse relation exists between local hypertrophy and miR‐133a. Reduced miR‐133a correlated with increased CTGF levels but not with SRF and NFATc4.

Background: Empyema is a well-known complication of pneumonia, with high morbidity and mortality rates. This warrants direct treatment either with antibiotics and chest tube drainage or surgery. With less invasive surgical approaches such as uniportal video-assisted thoracoscopic surgery (uVATS), surgical intervention gets a more prominent role early on in the treatment of empyema. The aim of this study was to compare uVATS with the complete VATS (cVATS) approach in empyema, with respect to postoperative complications, hospital length of stay and mortality.Methods: All cases of empyema that were treated surgically in our hospital between 2006 and 2019 were included in a retrospective database. The preferential surgical approach changed from cVATS from 2006 to 2015, towards uVATS from 2016 and on, based on the experience of the surgical team. The database included pre-and postoperative data, as well as peropartive characteristics.Results: One hundred and thirty-seven patients were treated with cVATS and 49 with uVATS. Apart from a slightly reduced kidney function in the uVATS group (57.3±6.3 vs. 71.4±17.2 mL/min/1.73 m 2 , P≤0.001), there were no significant baseline differences in patient characteristics. The duration of uVATS was comparable to cVATS (70±17 vs. 56±23 min, P=0.240), and with low per-and postoperative complications.The postoperative hospital stay was equal in both groups (19±13 vs. 20±15 days, P=0.320). There were no statistically significant differences in postoperative complications or death.Conclusions: Uniportal VATS is a feasible and safe technique for the use in patients with empyema requiring surgery. Even if decortication in stage III empyema is required this can be performed by uniportal VATS.

Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR) and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r  =  .86 for mice/rats and r  =  .98 for canine; both p < .001). After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR (r  =  .91, p < .001). CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis.

Recent studies have shown the efficacy of myocardial strain estimated using speckle tracking echocardiography (STE) in predicting response to cardiac resynchronisation therapy. This study focuses on circumferential strain patterns, comparing STE-acquired strains to tagged-magnetic resonance imaging (MRI-T). Second, the effect of regularisation was examined. Two-dimensional parasternal ultrasound (US) and MRI-T data were acquired in the left ventricular short-axis view of canines before (n = 8) and after (n = 9) left bunch branch block (LBBB) induction. US-based strain analysis was performed on Digital Imaging and Communications in Medicine data at the mid-level using three overall methods ("Commercial software," "Basic block-matching," "regularised block-matching"). Moreover, three regularisation approaches were implemented and compared. MRI-T analysis was performed using SinMod. Normalised regional circumferential strain curves, based on standard six or septal/lateral segments, were analysed and cross-correlated with MRI-T data. Systolic strain (SS) and septal rebound stretch (SRS) were calculated and compared. Overall agreement of normalised circumferential strain was good between all methods on a global and regional level. All STE methods showed a bias (4% strain) toward higher SS estimates. Pre-LBBB, septal and lateral segment correlation was excellent between the Basic (mean r = 0.96) and regularised (mean r = 0.97) methods and MRI-T. The Commercial method showed a significant discrepancy between the two walls (septal r = 0.94, lateral r = 0.68). Correlation with MRI-T reduced between pre-and post-LBBB (Commercial r = 0.79, Basic r = 0.82, mean regularised r = 0.86). Septal strain patterns and SRS varied with the STE software and type of regularisation, with all STE methods estimating nonzero SRS values pre-LBBB. Absolute values showed moderate agreement, with a bias for higher strain from STE. SRS varied with the type of software and extra regularisation applied. Open efforts are needed to understand the underlying causes of differences between STE methods before standardisation can be achieved. This is particularly important given the apparent clinical value of strain-based parameters such as SRS.