Correlation between inflammation state and successful medical cardioversion using bepridil for refractory atrial fibrillation

AbstractBackgroundIt has been reported that inflammation is associated with long-term maintenance of sinus rhythm after electrical cardioversion for non-valvular atrial fibrillation (AF). However, the relation between high-sensitive C-reactive protein (hs-CRP) and the recurrence of AF after medical cardioversion is unknown. On the other hand, bepridil is very effective in restoring sinus rhythm for patients with refractory AF.Methods and resultsIn 119 patients with non-valvular AF lasting >6 months who failed to maintain sinus rhythm after medical cardioversion without bepridil or electrical cardioversion, we prescribed bepridil. We divided our patients into success group who maintained sinus rhythm for at least 6 months using bepridil and failure group, and compared the following parameters, which were measured just before prescription of bepridil, between the two groups: hs-CRP as a marker of inflammation, left ventricular end-diastolic dimension, ejection fraction, and left atrial dimension as echocardiographic markers, and the incidence of dyslipidemia, hypertension, and diabetes mellitus. After the treatment with bepridil, 57 patients converted to sinus rhythm; however, 12 patients among these 57 patients could not maintain sinus rhythm. Therefore, the success group consisted of 45 patients (38%). Univariate analysis revealed that left atrial dimension and the value of hs-CRP were significantly lower and ejection fraction was significantly higher in the success group than the failure group. Multivariate analysis showed that hs-CRP and left atrial dimension were independent factors for AF recurrence.ConclusionsBepridil is effective in restoring sinus rhythm for refractory AF patients. Inflammation, in addition to left atrial dimension, may be associated with successful cardioversion using bepridil

High-density activation map of atrial tachycardia within left atrial appendage

Identification of the critical isthmus of the reentrant tachycardia is essential to maximize the effect of catheter ablation (CA) and to minimize the myocardial injury of CA. An 81-year-old woman presented recurrent palpitations after CA of atrial fibrillation (AF) and atrial tachycardia (AT). She had moderate aortic valve stenosis and coronary artery disease. She had received a pulmonary vein isolation, left atrial (LA) posterior wall isolation, and LA anterior linear ablation for atrial fibrillation 1 year prior. At the start of the procedure, she was in sinus rhythm. Atrial burst pacing induced an AT (230msec). High-density mapping revealed a figure-of-eight activation pattern within the LA appendage (LAA), accounting for 99% of the tachycardia cycle length. The critical isthmus was identified at the mid LAA and the local electrogram of the critical isthmus was not fractionated. A single radiofrequency application at the critical isthmus of the AT, terminated the AT. She was free from any ATs for 28 months.Radiofrequency ablation of the localized reentrant AT was usually performed targeting long fractionated electrograms. In our case, the local electrogram at the critical isthmus was not fragmented compared with the LAA distal part. Long fractionated electrograms were recorded at a more distal part of the LAA than the common isthmus and we could avoid the potential risk of a perforation. A recent developed 3-dimensional electro-anatomical mapping system can identify the critical isthmus and allow us to select a new therapeutic strategy for a critical isthmus ablation of an AT within the LAA

Importance of left ventricular minimal pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction

AbstractObjectives. This study was designed to assess whether the transmitral flow velocity pattern provides an estimation of left atrial pressure irrespective of the presence of left ventricular systolic dysfunction and, if not, to clarify the mechanism.Background. The pulsed Doppler transmitral flow velocity pattern, particularly peak early diastolic filling velocity, has been shown to change in parallel with left atrial pressure. However, extremely elevated left atrial pressure in association with heart failure does not necessarily cause an increase in peak early diastolic filling velocity in patients.Methods. Left atrial pressure was elevated with intravenous saline infusion in 11 dogs (normal left ventricular function group) and hemodynamic, transesophageal Doppler echocardiographic and M-mode echocardiographic variables were recorded at three different loading levels. In another 12 dogs, left atrial pressure was elevated by production of left ventricular systolic dysfunction with the stepwise injection of microspheres into the left coronary artery (left ventricular dysfunction group) and the same set of recordings was obtained at three different levels of dysfunction.Results. Peak early diastolic filling velocity increased with left atrial pressure in the normal left ventricular function group and correlated with mean left atrial pressure (r = 0.61, p < 0.01) and early diastolic left atrial to left ventricular crossover pressure (r = 0.71, p < 0.01). In contrast, peak early diastolic filling velocity did not increase with left atrial pressure in the left ventricular dysfunction grtup and did not correlate with mean left atrial pressure (r = −0.05) or the crossover pressure (r = 0.06). Peak early diastolic filling velocity correlated well with the difference between the crossover pressure and left ventricular minimal pressure in the left ventricular dysfunction group (r = 0.64, p < 0.01). In contract to peak early diastolic filling velocity, deceleration time of the early diastolic filling wave correlated with mean left atrial pressure and the crossover pressure irrespective of the primary cause of preload alteration (r = −0.54, r = −0.59, p < 0.01 respectively, n = 69 for all data).Conclusions. Preload dependency of the Doppler transmitral flow velocity pattern is hampered if an increase in left atrial pressure is due to left ventricular systolic dysfunction. In this setting, the increase in left ventricular minimal pressure due to left ventricular systolic dysfunction cancels the effect of the increase in left atrial pressure on the flow velocity pattern

Linear Population Allocation by Bistable Switches in Response to Transient Stimulation

<div><p>Many cellular decision processes, including proliferation, differentiation, and phenotypic switching, are controlled by bistable signaling networks. In response to transient or intermediate input signals, these networks allocate a population fraction to each of two distinct states (e.g. OFF and ON). While extensive studies have been carried out to analyze various bistable networks, they are primarily focused on responses of bistable networks to sustained input signals. In this work, we investigate the response characteristics of bistable networks to transient signals, using both theoretical analysis and numerical simulation. We find that bistable systems exhibit a common property: for input signals with short durations, the fraction of switching cells increases linearly with the signal duration, allowing the population to integrate transient signals to tune its response. We propose that this allocation algorithm can be an optimal response strategy for certain cellular decisions in which excessive switching results in lower population fitness.</p></div

Response of a positive-feedback model to pulse inputs.

<p>(A) Triggering a bistable positive-feedback model with a pulse. (B) Simulation (open circles) vs. theoretical prediction (solid lines) of activation probability as a function of pulse duration. The black arrow indicates increasing stimulus intensity. The activation probability increases linearly with the duration, when the latter is small. Inset shows intermediate signal transformation function. (C) The transition rate dictates the linear dependence, and increases with increasing stimulus intensity. Open circles and lines indicate theoretical and numerical predictions, respectively. (D) The pulse strength can be monotonically scaled upstream of the bistable decision module without affecting the characteristic activation property. Here, we use a Hill function with coefficient <i>n</i> = 2 as the transformation function (shown in inset).</p