Feasibility of In-Vivo Simulation of Acute Hemodynamics in Human Atrial Fibrillation.

This study evaluated hemodynamic feasibility and reproducibility of a new method for in vivo simulation of human atrial fibrillation (AF). The method was tested during sinus rhythm in 10 patients undergoing catheter ablation for AF. A simple electronic device was assembled that allowed triggering a cardiac stimulator by predefined series of RR intervals. Irregular RR interval sequences with a mean heart rate of 90/min and 130/min were obtained from ECG recordings of another patients with AF. Simultaneous atrioventricular pacing was delivered by catheters placed inside the coronary sinus and at the His bundle region. Hemodynamic effect of the simulated AF was assessed by invasive measurement of the left ventricular (LV) pressure, dP/dt, and Tau. Compared to regular pacing at the same mean heart rate, the simulated AF significantly impaired the LV both systolic and diastolic function. Repeated AF pacing in the same patients generated similar LV hemodynamics. The proposed method provides a realistic and reproducible in-vivo model of AF. It can be exploited for investigation of the hemodynamic consequences of AF in various patient populations

Characteristics of the template AF sequences.

<p>The figure shows histograms of the RR intervals and of the absolute differences of the subsequent RR intervals that were contained in the template AF sequences. It can be seen that both sequences contained a broad range of homogenously distributed RR intervals, which enabled to study the effects of heart rhythm irregularity. The dark bars represent mean cycle length (667 ms and 462 ms—i.e., 90/min and 130/min, respectively).</p

General principle of the method for simulation of AF.

<p>(A) QRS complexes were identified in an Holter ECG recording of AF to obtain a text string of the corresponding RR intervals. (B) The sequence of RR intervals was loaded to an Arduino-based microcomputer. The microcomputer generated square-wave pulses according to the RR interval sequence. (C) The pulses from the microcomputer were sensed by a cardiac stimulator, which was set to a sense-pace mode. (D) Pacing was performed by catheters in the coronary sinsus (i.e., left atrial pacing) and at the His bundle region. A pigtail cathter was inserted antegradely to measure the LV pressure.</p

Characteristics of the study population.

<p>Characteristics of the study population.</p

Effect of the simulated AF on the LV performance.

<p>The colored lines represent average values in the individual patients during three different pacing modes (atrial regular [reg], simultaneous atrioventricular [AV], simulated AF [AF]) at two different heart rates (90/min and 130/min). The black line with the errorbars represents mean and standard errors. */**/*** = P-value <0.5/<0.01/<0.001 by paired t-test with Holm’s correction; n.s. = non-significant difference (P-value > 0.5);</p

Reproducibility of the LV hemodynamics during two separate runs of simulated AF.

<p>(A) The colored lines represent average values in the individual patients obtained at two separate runs of the simulated AF. The black line with the errorbars represent mean and standard errors of all the patients. The p values were obtained by a paired t-test. (B) The graph shows excellent correlation between LV systolic pressure measured in the same patient during two separate runs of simulated AF. The data points were pooled from all the patients.</p

Sample of ECG with corresponding LV pressure signal during simulated AF.

<p>The figure shows a 10s sample of ECG and a corresponding LV pressure tracing recorded in all the study patients during two separate runs of the simulated AF. It can be appreciated that (i) the His pacing generated narrow QRS complexes thus indicating intrinsic activation of the ventricles, (ii) the RR intervals followed the same pattern in all the patients at both runs, (iii) the simulated AF generated similar LV pressure tracings among all the patients, (iv) the LV pressure tracings were almost identical within each patient at the two separate runs. Pt = patient.</p

Real-time measurement of ICD lead motion during stereotactic body radiotherapy of ventricular tachycardia

Background: Here we aimed to evaluate the respiratory and cardiac-induced motion of a ICD lead used as surrogate in the heart during stereotactic body radiotherapy (SBRT) of ventricular tachycardia (VT). Data provides insight regarding motion and motion variations during treatment. Materials and methods: We analyzed the log files of surrogate motion during SBRT of ventricular tachycardia performed in 20 patients. Evaluated parameters included the ICD lead motion amplitudes; intrafraction amplitude variability; correlation error between the ICD lead and external markers; and margin expansion in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions to cover 90% or 95% of all amplitudes. Results: In the SI, LL, and AP directions, respectively, the mean motion amplitudes were 5.0 ± 2.6, 3.4. ± 1.9, and 3.1 ± 1.6 mm. The mean intrafraction amplitude variability was 2.6 ± 0.9, 1.9 ± 1.3, and 1.6 ± 0.8 mm in the SI, LL, and AP directions, respectively. The margins required to cover 95% of ICD lead motion amplitudes were 9.5, 6.7, and 5.5 mm in the SI, LL, and AP directions, respectively. The mean correlation error was 2.2 ± 0.9 mm. Conclusions: Data from online tracking indicated motion irregularities and correlation errors, necessitating an increased CTV-PTV margin of 3 mm. In 35% of cases, the motion variability exceeded 3 mm in one or more directions. We recommend verifying the correlation between CTV and surrogate individually for every patient, especially for targets with posterobasal localization where we observed the highest difference between the lead and CTV motion

Membrane-type MMPs are indispensable for placental labyrinth formation and development

The membrane-type matrix metalloproteinases (MT-MMPs) are essential for pericellular matrix remodeling in late stages of development, as well as in growth and tissue homeostasis in postnatal life. Although early morphogenesis is perceived to involve substantial tissue remodeling, the roles of MT-MMPs in these processes are only partially characterized. Here we explore the functions of 2 prominently expressed MT-MMPs, MT1-MMP and MT2-MMP, and describe their roles in the process of placental morphogenesis. The fetal portion of the placenta, in particular the labyrinth (LA), displays strong overlapping expression of MT1-MMP and MT2-MMP, which is critical for syncytiotrophoblast formation and in turn for fetal vessels. Disruption of trophoblast syncytium formation consequently leads to developmental arrest with only a few poorly branched fetal vessels entering the LA causing embryonic death at embryonic day 11.5. Through knockdown of MMP expression, we demonstrate that either MT1-MMP or MT2-MMP is crucial specifically during development of the LA. In contrast, knockdown of MT-MMP activity after LA formation is compatible with development to term and postnatal life. Taken together these data identify essential but interchangeable roles for MT1-MMP or MT2-MMP in placental vasculogenesis and provide the first example of selective temporal and spatial MMP activity required for development of the mouse embryo

Assessment of electrical dyssynchrony in cardiac resynchronization therapy: 12-lead electrocardiogram vs. 96-lead body surface map

Aims The standard deviation of activation time (SDAT) derived from body surface maps (BSMs) has been proposed as an optimal measure of electrical dyssynchrony in patients with cardiac resynchronization therapy (CRT). The goal of this study was two-fold: (i) to compare the values of SDAT in individual CRT patients with reconstructed myocardial metrics of depolarization heterogeneity using an inverse solution algorithm and (ii) to compare SDAT calculated from 96-lead BSM with a clinically easily applicable 12-lead electrocardiogram (ECG). Methods and results Cardiac resynchronization therapy patients with sinus rhythm and left bundle branch block at baseline (n = 19, 58% males, age 60 +/- 11 years, New York Heart Association Classes II and III, QRS 167 +/- 16) were studied using a 96-lead BSM. The activation time (AT) was automatically detected for each ECG lead, and SDAT was calculated using either 96 leads or standard 12 leads. Standard deviation of activation time was assessed in sinus rhythm and during six different pacing modes, including atrial pacing, sequential left or right ventricular, and biventricular pacing. Changes in SDAT calculated both from BSM and from 12-lead ECG corresponded to changes in reconstructed myocardial ATs. A high degree of reliability was found between SDAT values obtained from 12-lead ECG and BSM for different pacing modes, and the intraclass correlation coefficient varied between 0.78 and 0.96 (P < 0.001). Conclusion Standard deviation of activation time measurement from BSM correlated with reconstructed myocardial ATs, supporting its utility in the assessment of electrical dyssynchrony in CRT. Importantly, 12-lead ECG provided similar information as BSM. Further prospective studies are necessary to verify the clinical utility of SDAT from 12-lead ECG in larger patient cohorts, including those with ischaemic cardiomyopathy