Correction: Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.

[This corrects the article DOI: 10.1371/journal.pone.0274415.].

Multimodality imaging to identify lipid-rich coronary plaques and predict periprocedural myocardial injury: Association between near-infrared spectroscopy and coronary computed tomography angiography.

Background: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). Methods: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. Results: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). Conclusion: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.

Diagnostic Accuracy of Artificial Intelligence-Based Angiography-Derived Fractional Flow Reserve Using Pressure Wire-Based Fractional Flow Reserve as a Reference.

BACKGROUND: Angiographic fractional flow reserve (angioFFR) is a novel artificial intelligence (AI)-based angiography-derived fractional flow reserve (FFR) application. We investigated the diagnostic accuracy of angioFFR to detect hemodynamically relevant coronary artery disease.Methods and Results: Consecutive patients with 30-90% angiographic stenoses and invasive FFR measurements were included in this prospective, single-center study conducted between November 2018 and February 2020. Diagnostic accuracy was assessed using invasive FFR as the reference standard. In patients undergoing percutaneous coronary intervention, gradients of invasive FFR and angioFFR in the pre-senting segments were compared. We assessed 253 vessels (200 patients). The accuracy of angioFFR was 87.7% (95% confidence interval [CI] 83.1-91.5%), with a sensitivity of 76.8% (95% CI 67.1-84.9%), specificity of 94.3% (95% CI 89.5-97.4%), and area under the curve of 0.90 (95% CI 0.86-0.93%). AngioFFR was well correlated with invasive FFR (r=0.76; 95% CI 0.71-0.81; P<0.001). The agreement was 0.003 (limits of agreement: -0.13, 0.14). The FFR gradients of angioFFR and invasive FFR were comparable (n=51; mean [±SD] 0.22±0.10 vs. 0.22±0.11, respectively; P=0.87). CONCLUSIONS: AI-based angioFFR showed good diagnostic accuracy for detecting hemodynamically relevant stenosis using invasive FFR as the reference standard. The gradients of invasive FFR and angioFFR in the pre-stenting segments were comparable.

Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys.

Human in vitro oogenesis provides a framework for clarifying the mechanism of human oogenesis. To create its benchmark, it is vital to promote in vitro oogenesis using a model physiologically close to humans. Here, we establish a foundation for in vitro oogenesis in cynomolgus (cy) monkeys (Macaca fascicularis): cy female embryonic stem cells harboring one active and one inactive X chromosome (Xa and Xi, respectively) differentiate robustly into primordial germ cell-like cells, which in xenogeneic reconstituted ovaries develop efficiently into oogonia and, remarkably, further into meiotic oocytes at the zygotene stage. This differentiation entails comprehensive epigenetic reprogramming, including Xi reprogramming, yet Xa and Xi remain epigenetically asymmetric with, as partly observed in vivo, incomplete Xi reactivation. In humans and monkeys, the Xi epigenome in pluripotent stem cells functions as an Xi-reprogramming determinant. We further show that developmental pathway over-activations with suboptimal up-regulation of relevant meiotic genes impede in vitro meiotic progression. Cy in vitro oogenesis exhibits critical homology with the human system, including with respect to bottlenecks, providing a salient model for advancing human in vitro oogenesis.

Relationship between tissue characteristics and mechanical properties of coronary plaques: a comparison between integrated backscatter intravascular ultrasound (IVUS) and speckle-tracking IVUS.

High-risk coronary plaques have certain morphological characteristics. Thus, comprehensive assessment is needed for the risk stratification of plaques in patients with coronary artery disease. Integrated backscatter intravascular ultrasound (IB-IVUS) has been used successfully used to evaluate the tissue characteristics of coronary plaques; however, the mechanical properties of plaques have been rarely assessed. Therefore, we developed Speckle-tracking IVUS (ST-IVUS) to evaluate the mechanical properties of coronary plaque. This study aimed to evaluate the relation between the tissue characteristics of coronary plaques using IB-IVUS and their mechanical properties using ST-IVUS. We evaluated 95 non-targeted plaques in 95 patients undergoing elective percutaneous coronary intervention to the left anterior descending artery. We set regions of interest (ROIs) in the cross-sectional images of coronary plaques where we divided 120 degree plaques into four quadrants (every 30 degrees), with the center at the area of maximum atheroma thickness. We measured relative calcification area (%CA, relative fibrous area (%FI) and relative lipid pool area (%LP) in a total of 380 ROIs. In ST-IVUS analysis, we measured strain in the circumferential direction of the lumen area (LA strain: %), the external elastic membrane area strain (EEM strain: %), and strain in the radial direction (radial strain: %). On global cross-sectional area IB-IVUS analysis, the %CA was 1.2 ± 1.2%; the %FI was 49.0 ± 15.9%, and the %LP was 49.7 ± 16.5%. In ST-IVUS analysis, the LA strain was 0.67 ± 0.43%; the EEM strain was 0.49 ± 0.33%, and the radial strain was 2.02 ± 1.66%. On regional analysis, the %LP was not associated with the LA strain (r = - 0.002 p = 0.97), the EEM strain (r = - 0.05 p = 0.35), or with the radial strain (r = - 0.04 p = 0.45). These trends were seen between the %FI and the LA strain (r = 0.02 p = 0.74), the %FI and the EEM strain (r = 0.05 p = 0.35), and the %FI and the radial strain (r = 0.04 p = 0.50). A significant correlation was only observed between the %CA and the LA strain (r = - 0.15 p = 0.0038). Our findings indicate that the associations between mechanical properties and tissue characteristics lacked statistical significance, more often than not, and that it is necessary to evaluate the mechanical properties as well as plaque characteristics for risk stratification of coronary plaques.

Observation of plaque behavior and tissue characterization of coronary plaque using speckle tracking intravascular ultrasound (ST-IVUS) and iMap imaging system.

Tissue characterization plays an important role in the development of acute coronary syndromes. iMap is an intravascular ultrasound (IVUS) tissue characterization system that provides useful information by reconstructing color-coded maps. Mechanical properties due to dynamic mechanical stress during a cardiac cycle may also trigger vulnerable plaque. Speckle tracking IVUS (ST-IVUS) has been introduced to observe plaque behavior in relation to mechanical properties. We report the case of an 84-year-old woman with stable coronary artery disease who underwent percutaneous coronary intervention, at which time IVUS demonstrated mainly three low echoic areas like lipid pools with thick fibrous caps. Pathological evaluation with iMap revealed that one low echoic area was occupied with necrotic tissue and that the other two areas occupied fibrotic. Although those tissue characterizations were different, they showed similar stretching behavior at systole by ST-IVUS which depicted plaque behavior from IVUS images using a color mapping. The mechanical properties of individual coronary plaques may differ depending on the tissue disposition. It is necessary to consider mechanical properties using ST-IVUS as well as to evaluate tissue characterization in plaque risk stratification.

Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.

Lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies (Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests. We assessed 25 new and 4 existing Igs in a matrixed format using a multiplex electrochemiluminescence-based liquid immunoassay. A total of 841 paired Ig combinations were challenged with in vitro cultured LAM (cLAM) derived from MTB strains representing diverse phylogenetic lineages, alongside urinary LAM (uLAM) from the urine of adults with active pulmonary TB. Analytical sensitivity of down-selected Ig pairs was determined using MTB Aoyama-B cLAM, while diagnostic accuracy was determined using clinical samples. When testing cLAM, the reactivity of Ig pairs was similar across MTB lineages 1-4 but lineage 5:6 had significantly more reactivity among Ig pairs. Overall, 41 Ig pairs had a strong binding affinity to cLAM, as compared to the reference pair of S4-20/A194-01, and 28 Ig pairs therein exhibited a strong affinity for both cLAM and uLAM. Retrospective testing on clinical urine specimens demonstrated varying sensitivities (12-80%) and specificities (14-100%). The five top pairs had a similar analytical limit of detection to the reference pair but in four instances, the sensitivity and specificity with clinical uLAM samples was poor. Overall, epitopes presented by uLAM are different from cLAM, which may affect antibody performance when testing uLAM in patient samples. Several new Ig pairs had similar ranges of high sensitivity to cLAM but overall, there were no new candidate Ig pairs identified in this round of screening with increased performance with uLAM as compared to an existing optimal pair.

Development of 60 MHz integrated backscatter intravascular ultrasound and tissue characterization of attenuated signal coronary plaques that cause myocardial injury after percutaneous coronary intervention.

The purpose of the present study was to develop a 60 MHz integrated backscatter intravascular ultrasound (IB-IVUS) and to evaluate its usefulness for the detection of lipid area with backward attenuation of ultrasound signal (AT) that for the prediction of post-procedural myocardial injury (PMI) after percutaneous coronary intervention (PCI). In a pathological study, images were acquired from 221 cross-sections of 18 coronary arteries from 13 cadavers obtained at autopsy. In the clinical training study, we compared non-targeted plaques in 38 patients by a previous IB-IVUS system (38 MHz) and a new IB-IVUS system (60 MHz). In the clinical testing study, we included 70 consecutive patients who underwent PCI. Serum troponin-I was measured just before and 24 h after PCI to evaluate PMI. As the % microcalcification + % cholesterol cleft area increased, the attenuation of IB values increased (r = 0.56, p < 0.001). The slopes of regression lines of the area of each tissue component between 38 and 60 MHz IB-IVUS were excellent. The lipid pool area with AT tended to be more useful than that of the conventional lipid pool area for the prediction of PMI (p = 0.11). We developed a 60 MHz IB-IVUS imaging system for tissue characterization of coronary plaques. Cutoff value of purple color was the most reliable value for the prediction of PMI.

Clinical impact of PCSK9 inhibitor on stabilization and regression of lipid-rich coronary plaques: a near-infrared spectroscopy study.

AIMS: This study aimed to determine the effects of a proprotein convertase subtilisin-kexin type 9 inhibitor (PCSK9i) on coronary plaque volume and lipid components in patients with a history of coronary artery disease (CAD). METHODS AND RESULTS: This prospective, open-label, single-centre study analysed non-culprit coronary segments using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) at baseline and follow-up angiography. Following changes in the lipid-lowering treatment based on the most recent guideline, the enrolled subjects were divided into two groups: treatment with PCSK9i and statins (PCSK9i: 21 patients and 40 segments) and statins only (control: 32 patients and 50 segments). The absolute and percent LDL-C reductions were significantly greater in the PCSK9i group than in the control group (between group difference: 59.3 mg/dL and 46.4%; P < 0.001 for both). The percent reduction in normalized atheroma volume and absolute reduction in percent atheroma volume (PAV) were also significantly greater in the PCSK9i group (P < 0.001 for both). Furthermore, the PCSK9i group showed greater regression of maximal lipid core burden index for each of the 4-mm segments (maxLCBI4mm) than the control group (57.0 vs. 25.5; P = 0.010). A significant linear correlation was found between the percent changes in LDL-C and maxLCBI4mm (r = 0.318; P = 0.002), alongside the reduction in PAV (r = 0.386; P < 0.001). CONCLUSION: The lipid component of non-culprit coronary plaques was significantly decreased by PCSK9i. The effects of statin combined with PCSK9i might be attributed to the stabilization and regression of residual vulnerable coronary plaques in patients with CAD.

Stress Myocardial Perfusion Imaging Interpretation From the Viewpoint of Fractional Flow Reserve.

BACKGROUND: Myocardial perfusion imaging (MPI) and fractional flow reserve (FFR) are established approaches to the assessment of myocardial ischemia. Recently, various FFR cutoff values were proposed, but the diagnostic accuracy of MPI in identifying positive FFR using various cutoff values is not well established.Methods and Results:We retrospectively studied 273 patients who underwent stress MPI and FFR within a 3-month period. Results for FFR were obtained from 218 left anterior descending artery (LAD) lesions and 207 non-LAD lesions. Stress MPI and FFR demonstrated a good correlation in the detection of myocardial ischemia. However, the positive predictive value (PPV) of FFR for detecting MPI-positive lesions at the optimal FFR thresholds was insufficient (44% for LAD and 65% for non-LAD lesions). This was caused by a sharp drop in PPV at an FFR threshold of 0.7 or more. Notably, 41% of the lesions with normal MPI demonstrated FFRs <0.80. However, MPI-negative lesions had an extremely low lesion rate with FFR <0.65 (6%). Conversely, 78% and 41% of MPI-positive lesions had FFR <0.80 and <0.65, respectively. CONCLUSIONS: The data confirmed that decisions based on MPI are reasonable because MPI-negative patients have an extremely low rate of lesions with a FFR below the cutoff point for a hard event, and MPI-positive lesions include many lesions with FFR <0.65.

Macrocyclic Peptides that Selectively Inhibit the Mycobacterium tuberculosis Proteasome.

Treatment of tuberculosis (TB) currently takes at least 6 months. Latent Mycobacterium tuberculosis (Mtb) is phenotypically tolerant to most anti-TB drugs. A key hypothesis is that drugs that kill nonreplicating (NR) Mtb may shorten treatment when used in combination with conventional drugs. The Mtb proteasome (Mtb20S) could be such a target because its pharmacological inhibition kills NR Mtb and its genetic deletion renders Mtb unable to persist in mice. Here, we report a series of macrocyclic peptides that potently and selectively target the Mtb20S over human proteasomes, including macrocycle 6. The cocrystal structure of macrocycle 6 with Mtb20S revealed structural bases for the species selectivity. Inhibition of 20S within Mtb by 6 dose dependently led to the accumulation of Pup-tagged GFP that is degradable but resistant to depupylation and death of nonreplicating Mtb under nitrosative stress. These results suggest that compounds of this class have the potential to develop as anti-TB therapeutics.

In vivo validation of resting full-cycle ratio and diastolic pressure ratio: simultaneous measurement with instantaneous wave-free ratio.

The diastolic pressure ratio (dPR) and resting full-cycle ratio (RFR) are considered to be almost identical to the instantaneous wave-free ratio (iFR) in the retrospective analysis of pooled data. The aim of this study was to investigate the direct comparison of iFR and these new resting indexes in real world practice. Two pressure wires were inserted and placed in the distal part of the same coronary artery. The measurement of the iFR and the other resting indexes was performed simultaneously. A total of 54 lesions from 23 patients were subject to physiological study. In 49 lesions, iFR and other resting indexes were also measured in hyperemic conditions. The general correlation between iFR and other resting indexes was excellent in both resting and hyperemic conditions (r2 = 0.99; mean difference - 0.001 ± 0.021; p < 0.001; and r2 = 0.99; mean difference - 0.012 ± 0.025; p < 0.001, respectively). This correlation was maintained in various subgroup analyses. A diagnostic change between iFR and other resting indexes occurred in three cases (3%) when a fixed cut-off point (≤ 0.89) was applied. There was no diagnostic change when a hybrid zone (0.86 ≤ iFR ≤ 0.93) was considered. The new resting indexes and iFR showed very high correlation in real world practice. A diagnostic change only occurred in three cases (3%) when a fixed cut-off point (≤ 0.89) was applied.

Comparisons of Nonhyperemic Pressure Ratios: Predicting Functional Results of Coronary Revascularization Using Longitudinal Vessel Interrogation.

OBJECTIVES: The aim of this study was to investigate the accuracy of pre-percutaneous coronary intervention (PCI) predicted nonhyperemic pressure ratios (NHPRs) with actual post-PCI NHPRs and to assess the efficacy of PCI strategy using pre-PCI NHPR pullback. BACKGROUND: Predicting the functional results of PCI is feasible using pre-PCI longitudinal vessel interrogation with the instantaneous wave-free ratio (iFR), a pressure-based, adenosine-free NHPR. However, the reliability of novel NHPRs (resting full-cycle ratio [RFR] and diastolic pressure ratio [dPR]) for this purpose remains uncertain. METHODS: In this prospective, multicenter, randomized controlled trial, vessels were randomly assigned to receive pre-PCI iFR, RFR, or dPR pullback (50 vessels each). The pre-PCI predicted NHPRs were compared with actual NHPRs after contemporary PCI using intravascular imaging. The number and the total length of treated lesions were compared between NHPR pullback-guided and angiography-guided strategies. RESULTS: The predicted NHPRs were strongly correlated with actual NHPRs: iFR, r = 0.83 (95% confidence interval: 0.72 to 0.90; p < 0.001); RFR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001), and dPR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001). The number and the total length of treated lesions were lower with the NHPR pullback strategy than with the angiography-guided strategy, leading to physiological improvement. CONCLUSIONS: Predicting functional PCI results on the basis of pre-procedural RFR and dPR pullbacks yields similar results to iFR. Compared with an angiography-guided strategy, a pullback-guided PCI strategy with any of the 3 NHPRs reduced the number and the total length of treated lesions. (Study to Examine Correlation Between Predictive Value and Post PCI Value of iFR, RFR and dPR; UMIN000033534).

Primary Angiosarcoma in the Right Atrium Diagnosed by a Cardiac Tumor Biopsy Using Intracardiac Echocardiography.

A 47-year-old woman consulted a doctor due to a persistent cough. Computed tomography revealed a 30 mm × 60 mm intracardiac mass in the right atrium. Because of lung metastasis, her respiratory status did not allow a more invasive procedure, such as general anesthesia. Although intracardiac echocardiography (ICE) during percutaneous transcatheter biopsy (PTB) is not covered by medical insurance, we performed PTB under ICE guidance. Pathology and immunohistochemistry revealed primary cardiac angiosarcoma. Primary cardiac angiosarcoma is a rare tumor with a poor prognosis. After seven cycles of chemotherapy, the pulmonary metastasis was clearly improved. The patient is alive 18 months after the first consult, even though the mortality of angiosarcoma is high. ICE during PTB allowed us to choose appropriate chemotherapy and improve her pulmonary metastasis. ICE during PTB reduces the need for a diagnostic open-chest procedure that requires a more invasive approach.

Adduct Formation of Delamanid with NAD in Mycobacteria.

Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F420)-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM metabolites revealed covalent binding of reduced DLM with a nicotinamide ring of NAD derivatives (oxidized form) in DLM-treated Mycobacterium tuberculosis var. Bacille de Calmette et Guérin. Isoniazid-resistant mutations in the type II NADH dehydrogenase gene (ndh) showed a higher intracellular NADH/NAD ratio and cross-resistance to DLM, which were restored by complementation of the mutants with wild-type ndh Our data demonstrated for the first time the adduct formation of reduced DLM with NAD in mycobacterial cells and its importance in the action of DLM.

Relationships among pulmonary capillary wedge pressure, dry weight and natriuretic peptide in patients undergoing hemodialysis: a three-dimensional speckle tracking echocardiography study.

BACKGROUND: Although the evaluation of fluid status in hemodialysis (HD) patients is useful, relationship among pulmonary capillary wedge pressure (PCWP), dry body weight (DW) and natriuretic peptide has not been elucidated. In addition, there has been no objective marker for instantaneously monitoring hemodynamic improvement in response to HD. We previously reported that PCWP and time constant of left ventricular pressure decline (Tau) can be noninvasively estimated (ePCWP and eTau) by speckle tracking echocardiography (STE). The aim of this study was to elucidate the relationship among ePCWP, eTau, DW and natriuretic peptide in patients undergoing HD. METHODS: We measured ePCWP and body weight (BW) by STE in 81 patients and ANP and BNP by blood examination in 31 patients just before and after HD during sinus rhythm. RESULTS: The ePCWP decreased after HD, and this was associated with reductions in ln ANP, eTau and BW (r = 0.523, 0.271 and 0.814, respectively, p < 0.05). The % change in ePCWP was not correlated with the % change in ln BNP (p = 0.47). The change in ePCWP had a stronger correlation with the % change in BW than the change in any other parameters. CONCLUSIONS: The ePCWP is more sensitive to estimate the change in BW during HD than any other parameters such as ANP and BNP. These results indicated that a substantial amount of excess fluid can be assessed real-time by STE using ePCWP.

In situ nuclear DNA methylation in dilated cardiomyopathy: an endomyocardial biopsy study.

AIMS: Although distinct DNA methylation patterns have been reported, its localization and roles remain to be defined in heart failure. We investigated the cellular and subcellular localization of DNA methylation and its pathophysiological significance in human failing hearts. METHODS AND RESULTS: Using left ventricular (LV) endomyocardial biopsy specimens from 75 patients with dilated cardiomyopathy (DCM; age: 58 ± 14 years old, %female: 32%) and 20 patients without heart failure (controls; age: 56 ± 17 years old, %female: 45%), we performed immunohistochemistry and immunoelectron microscopy for methylated DNA, 5-methylcytosine (5-mC). We next investigated possible relations of the incidence of 5-mC-positive (%5-mC+ ) cardiomyocytes with clinicopathological parameters. Immunopositivity for 5-mC was detected in the cardiomyocytes and other cell types. The %5-mC+ cardiomyocytes was significantly greater in DCM hearts than in controls (57 ± 13% in DCM vs. 25 ± 12% in controls, P < 0.0001). The localization of 5-mC immunopositivity in cardiomyocyte nuclei coincided well with that of heterochromatin, as confirmed by immunoelectron microscopy. Substantial DNA methylation was also observed in interstitial non-cardiomyocytes, but the incidences did not differ between control and DCM hearts (39 ± 7.9% in DCM vs. 41 ± 10% in controls, P = 0.4099). In DCM patients, the %5-mC+ cardiomyocytes showed a significant inverse correlation with LV functional parameters such as heart rate (r = 0.2391, P = 0.0388), end-diastolic pressure (r = 0.2397, P = 0.0397), and ejection fraction (r = -0.2917, P = 0.0111) and a positive correlation with LV dilatation (volume index at diastole; r = 0.2442, P = 0.0347; and volume index at systole; r = 0.3136, P = 0.0062) and LV hypertrophy (mass index; r = 0.2287, P = 0.0484)-that is, LV remodelling parameters. No significant correlations between DNA methylation and the histological parameters of the biopsies, including cardiomyocyte hypertrophy, fibrosis, and inflammatory cell infiltration, were noted. CONCLUSIONS: The present study revealed increased nuclear DNA methylation in cardiomyocytes, but not other cell types, from DCM hearts, with predominant localization in the heterochromatin. Its significant relations with LV functional and remodelling parameters imply a pathophysiological significance of DNA methylation in heart failure.

Carotid Artery Stenting Using a Double-layer Micromesh Stent.

Carotid artery stenting (CAS) has recently emerged as a potential alternative to carotid endarterectomy (CEA) in Japan. However, one of its disadvantages is the higher incidence of ischemic complications than CEA, such as distal embolism during or after the procedure. Plaque protrusion (PP) through the stent strut after deployment of the stent has been suggested as one of the major causes of distal embolism, especially in patients with unstable plaques. The need for increased plaque coverage to reduce the risk of PP through the stent struts has led to the development of a double-layer micromesh stent (micromesh stent) system. This stent system has already been used clinically in European countries with good short- to medium-term follow-up results. Also clinical trials evaluating micromesh stents have been completed in Japan. Hence, usefulness of the micromesh stent for CAS is expected. According to the results of several clinical studies, CAS with the double-layer micromesh stent has the potential to minimize distal embolism during or after the procedure even in patients with unstable plaques. However, it may not be suitable for emergency CAS at this point. Also, since results of only short- to medium-term follow-up have been reported, longer-term follow-up will be required in the near future.

Neovascularization in pericarditis: a possible etiology of hemopericardium.

Hemorrhagic pericardial effusion is life-threatening and mostly occurs during pericarditis; however, its underlying mechanism is unclear. We report a case of pericardial hematoma with obvious hemorrhage. A 56-year-old man without prior chest trauma presenting with exertional dyspnea and abdominal fullness was treated for idiopathic pericarditis. The echocardiogram showed a thickened pericardium with effusion. Imaging showed extravasation and neovascularization. Following ineffective pharmacotherapy, we performed pericardiectomy. The site of bleeding was undetectable. Because parietal pericardiectomy with hematoma evacuation did not improve diastolic function, we removed the epicardium. During the follow-up period, the patient remained almost asymptomatic. We identified neovascularization as the potential source of idiopathic pericardial hemorrhage.