Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping.

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm × 2 mm or 10 mm x 10 mm, with a 100 × 100 resolution (20 µm/pixel or 100 µm/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

Prediction of relapse after discontinuation of biologic agents by ultrasonographic assessment in patients with rheumatoid arthritis in clinical remission: high predictive values of total gray-scale and power Doppler scores that represent residual synovial inflammation before discontinuation.

OBJECTIVE: This prospective study aimed to determine whether the comprehensive ultrasonographic assessment of synovial inflammation predicts relapse after discontinuation of treatment with a biologic agent in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: RA patients in clinical remission (Disease Activity Score in 28 joints [DAS28] <2.6) receiving treatment with a biologic agent who agreed to discontinue the treatment were recruited. Patients underwent a comprehensive ultrasound scan on 134 synovial sites in 40 joints and were prospectively followed up for 6 months. Physicians who evaluated the patients during the study period were blinded to the baseline ultrasound findings. RESULTS: Forty-two patients receiving either a tumor necrosis factor antagonist or tocilizumab were enrolled. Using the optimal cutoff values determined by receiver operating characteristic curve analysis, relapse rates were significantly higher in patients whose total ultrasound scores at discontinuation were high than in those whose total ultrasound scores were low (P < 0.001 for both total gray-scale and power Doppler scores), whereas the difference between high and low DAS28 was not statistically significant (P = 0.158 by log rank test). Positive and negative predictive values were 80.0% and 73.3% for the total gray-scale score and 88.9% and 74.2% for the total power Doppler score, respectively. CONCLUSION: In RA patients in clinical remission receiving treatment with a biologic agent, residual synovial inflammation determined by comprehensive ultrasound assessment predicted relapse within a short term after discontinuation of the treatment. Our data provide a rationale and groundwork to conduct a large-scale study for establishment of ultrasound-based strategies to optimize the period of treatment with a biologic agent.

Assessment of echo-attenuated plaque by optical coherence tomography and its impact on post-procedural creatine kinase-myocardial band elevation in elective stent implantation.

OBJECTIVES: This study examined morphological characteristics of echo-attenuated plaques by optical coherence tomography (OCT) and evaluated their influence on creatine kinase-myocardial band (CK-MB) elevation after percutaneous coronary intervention (PCI) in patients with elective stent implantation. BACKGROUND: Recent intravascular ultrasound studies have described atherosclerotic plaques with echo attenuation (EA) without associated bright echoes that are correlated with no-reflow phenomenon after PCI. METHODS: We studied 135 native de novo culprit coronary lesions in 135 patients with normal pre-PCI CK-MB levels (28 with unstable angina; 107 with stable angina) who underwent intravascular ultrasound and OCT examinations before elective stent implantation. The lesions were divided into 2 groups based on the presence or absence of EA, and OCT findings were compared. We then determined predictors of post-PCI CK-MB elevation. RESULTS: EA was found in 47 (34.8%) lesions and was associated with the presence of OCT-derived thin-capped fibroatheroma, ruptured plaques, greater lipid content, intravascular ultrasound-derived large reference and plaque area, lesion eccentricity, and microcalcification. Elevated CK-MB levels were observed in 36 (26.7%) lesions, and significantly more frequently in lesions with EA than without. In multivariable analysis, EA (odds ratio [OR]: 3.49; 95% confidence interval [CI]: 1.53 to 7.93; p = 0.003) and OCT-derived ruptured plaque (OR: 2.92; 95% CI: 1.21 to 7.06; p = 0.017) were independent predictors of post-PCI CK-MB elevation. CONCLUSIONS: Atherosclerotic plaques with EA were associated with characteristics considered to be high risk or unstable. OCT examination showed an additive predictive value to the presence of EA for post-PCI CK-MB elevation.

Assessment of acute injuries and chronic intimal thickening of the radial artery after transradial coronary intervention by optical coherence tomography.

AIMS: Transradial coronary intervention (TRI) introduces a trauma to the radial artery (RA), possibly influencing quality as a bypass conduit if subsequently used. We sought to determine the acute and chronic effects of TRI on the RA by optical coherence tomography (OCT). METHODS AND RESULTS: Immediately after TRI completion, 73 RAs in 69 patients were examined. The sheath was pulled back 2 cm distal to the puncture site, and OCT imaging was performed. The acute injuries and intimal thickening were compared between first-TRI RAs and repeat-TRI RAs. Intimal tears were observed in 49 RAs (67.1%) and were more frequent in the distal than in the proximal RA (P = 0.001). Medial dissections were not uncommon (26 RAs, 35.6%). The frequency of acute injury was significantly higher in repeat-TRI RAs (P < 0.001). Intima/medial area, the maximum intimal thickness/medial thickness ratio, and per cent narrowing were all significantly greater in repeat-TRI RAs in the distal and proximal RA. Multivariate analysis revealed that a repeated TRI procedure was the only independent predictor of intimal thickening. CONCLUSION: Optical coherence tomography clearly demonstrated significant acute injuries and chronic intimal thickening of RA after TRI. Further study should evaluate the impact of these effects when TRI RAs are subsequently used as conduits, on long-term graft patency and on clinical outcomes after bypass surgery.