Epicardial flow in the right ventricular wall on echocardiography: A sign of chronic total occlusion of left anterior descending artery.

Transthoracic coronary Doppler echocardiography (TCDE) can be useful for the detection of chronic total occlusion (CTO) of the proximal left anterior descending coronary artery (LAD) noninvasively, by detecting retrograde flow through the distal LAD or its septal branch. This intriguing case report details the detection of abnormal blood flow in the right ventricular free wall by TCDE. This detection of abnormal flow may be useful to predict CTO of the LAD, even in the absence of retrograde flow in the LAD and its septal branch.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

The HTML version of this Article contained errors in Supplementary Figure S2 "Flowchart of the lyso-Gb3 screening and gene analysis in female patients", which have been detailed in the associated Correction.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.

Relationship between coronary diastolic pressure indexes during the wave-free period and a novel pressure-derived index: Diastolic pressure ratio at the optimal point.

OBJECTIVES: We aimed to determine the diastolic pressure ratio at the optimal point (DROP) using a simple measurement algorithm and to compare DROP with distal coronary-to-aortic pressure ratios during the wave-free period (PRWFP ) and at the mid-diastolic point (PRMD ). METHODS: Distal coronary and aortic pressures were measured from color pressure images of 440 beats in 48 patients with coronary stenoses. The DROP measurement point was 67% for one beat between the two rising points on the aortic pressure curve according to the distribution of the wave-free period and the mid-diastolic point. RESULTS: DROP correlated closely with PRWFP (r = 0.993, P < 0.0001) and PRMD (r = 0.997, P < 0.0001). The diagnostic efficiency was excellent (area under the receiver-operating characteristic curve, 0.997) for both PRWFP ≤ 0.89 (specificity, 0.99; sensitivity, 0.96) and PRMD ≤ 0.89 (specificity, 0.95; sensitivity, 1.00). CONCLUSIONS: A simple pressure-derived physiological marker of coronary stenosis, DROP, might represent other diastolic pressure indexes with a numerical equivalency to the instantaneous wave-free ratio. DROP can be measured automatically assuming that the rising points on the aortic pressure curve are detectable. However, further large-scale clinical investigations are needed to determine whether DROP could contribute to the further generalization of physiology-guided percutaneous coronary intervention.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

In the above article, we noticed that one female patient in the positive group (plasma lyso-Gb3 7.6 ng/ml, α-galactosidase A activity 4.9 nmol/h/ml) who presented at the neurology clinic was already diagnosed with Fabry disease before the current study. We excluded patients with a confirmed diagnosis of Fabry disease and those with relatives known to have Fabry disease. To accurately describe the information in the current study, we must exclude this patient from the analysis. We have accurately revised this information as follows.

Serial changes in the three-dimensional aspect of the side-branch ostium jailed by a drug-eluting stent assessed by optical coherence tomography.

The present study investigated serial changes in the three-dimensional (3D) aspect of the jailed side-branch (SB) ostium. We evaluated 32 patients who underwent examination with optical coherence tomography (OCT) both at baseline and at follow-up. After reconstruction of the 3D images, we classified the configuration of overhanging struts at the SB orifice into three groups according to the 3D aspect of the jailing configuration. The number of compartments divided by the stent strut was counted. The side-branch flow area (SBFA), i.e., the area of the SB ostium except for jailing struts, was measured by cut-plane analysis. Forty-eight SBs of 25 patients were analyzed. Thirteen SBs were classified as the No-jail type (N-type), 19 as the Simple-jail type (S-type; no longitudinal link at the carina), and 16 as the Complex-jail type (C-type; had a link at the carina). In the N-type, the SBFA was significantly increased at follow-up (P = 0.018). In the C-type, the SBFA was significantly decreased at follow-up (P = 0.002). Percent reduction of SBFA in the C-type group was significantly greater than that in the N-type or S-type groups (S-type vs. C-type P = 0.002, N-type vs. C-type P < 0.001). 3D-OCT images showed that some of the compartments were filled with tissue. The number of compartments was significantly decreased at follow-up (P < 0.001). In the C-type group, the SBFA was significantly decreased and small compartments were filled with tissue. These findings suggest that stent jail complexity is associated with the progression of SB ostial stenosis.

Differences of side branch jailing between left main-left anterior descending artery stenting and left main-left circumflex artery stenting with Nobori biolimus-eluting stent.

The aim of this study is to indicate differences of side branch jailing between the left main (LM)-left anterior descending artery (LAD) stenting and the LM-left circumflex artery (LCx) stenting. Thirty-one patients who underwent single-stenting using a two-link ten-crowns biolimus-eluting stent (Japanese design of BES, J-BES) and subsequent kissing balloon dilation (KBD) on an LM bifurcation with optical coherence tomography (OCT) were divided into two groups according to the stented vessel. Bifurcation angles were measured by three-dimensional (3D) quantitative coronary analysis. The jailing pattern on a side branch ostium was evaluated by stent-enhanced 3D-OCT. Incomplete stent apposition (ISA) after KBD was compared between the stented vessels. The to-be-stented angle of the LM-LCx stenting (n = 11) was significantly steeper than that of the LM-LAD stenting (n = 20) (132.6° ± 16.9° vs. 150.7° ± 10.6°, p < 0.01). The incidence of the free carina type, which has no stent links bridging from a carina, in the LM-LCx stenting was significantly higher than that in the LM-LAD stenting (90.9 vs. 45.0 %, p = 0.02). The percentage of ISA at the bifurcation segment in the LM-LCx stenting was significantly smaller than that in the LM-LAD stenting (4.4 ± 8.2 vs. 12.7 ± 9.2 %, p = 0.0003). This study showed, by higher incidence of the favorable configuration, that the LM-LCx stenting achieved a smaller percentage of ISA than the LM-LAD stenting. These insights may help guide LM bifurcation stenting with J-BES.

Comparison of neointimal coverage and extra-stent lumen between sirolimus and everolimus-eluting stent using optical coherence tomography.

The external lumen of a stent [defined as extra-stent lumen (ESL)] assessed by optical coherence tomography (OCT) may be related to the risk of thrombus formation after sirolimus-eluting stent (SES) implantation. An everolimus-eluting stent (EES) might provide relatively minimal inflammatory reaction and appropriate neointimal coverage. The purpose of this study was to compare the neointimal thickness and ESL between SES and EES. Patients who underwent OCT examination more than 7 months after either SES or EES implantation were enrolled. Stent area (SA), lumen area (LA), neointimal area (NIA) and neointimal thickness (NIT) of each strut were measured at 1-mm intervals between stented segments. The area, angle (summation per cross-section) and depth (maximum distance from adjacent vessel surface to the outline of stent) of ESL were analyzed. A total of 49 lesions were included (SES n = 20, EES n = 29). Mean follow-up period was 11 months. A total of 998 cross-sections and 9874 struts were analyzed. There were no differences in stent area, lumen area and neointimal area (SA: 6.01 ± 1.60 vs. 6.02 ± 1.40 mm(2), p = 0.572, LA: 5.37 ± 1.52 vs. 5.29 ± 1.34 mm(2), p = 0.692, NIA: 0.64 ± 0.49 vs. 0.72 ± 0.37 mm(2), p = 0.493). Mean NIT of SES and EES were 0.11 ± 0.05 and 0.10 ± 0.05 mm, respectively (p = 0.367). Conversely, area, angle and depth of ESL in SES group were significantly greater than those in EES group (0.20 ± 0.39 vs. 0.03 ± 0.09 mm(2), p < 0.001, 56.2 ± 59.1° vs. 20.1 ± 41.9°, p < 0.001, 0.10 ± 0.09 vs. 0.03 ± 0.03 mm, p < 0.001). OCT showed that the efficacy of neointimal growth suppression is similar between SES and EES, whereas the adverse vascular response after EES implantation is smaller than that after SES implantation.

Association of apixaban therapy and prothrombin time in patients with atrial fibrillation.

BACKGROUND: This study evaluated whether measuring prothrombin time (PT) using particular reagents of interest predicted apixaban-associated anticoagulant activity in Japanese patients with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Two reagents, Shinplastin Excel S and Coagpia PT-N, were used to evaluate PT under apixaban therapy. From June 2013 to February 2014, 103 NVAF patients were recruited, and PT was measured at 3 time points: (1) anytime in the outpatient clinic, (2) at peak, and (3) at trough. In spike-in experiments using pooled citrated normal human platelet-poor plasma with these PT reagents, apixaban prolonged PT values in a concentration-dependent manner. PT values significantly correlated between both reagents (r=0.97) in outpatients. PT values in outpatients taking 5-mg apixaban bid were significantly prolonged and had wide inter- and intraindividual variability. Peak values were significantly higher than trough values, with both values higher than normal. The dose change of apixaban from 5 mg bid to 2.5 mg bid in outpatients halved the degree of PT prolongation in each NVAF patient. CONCLUSIONS: The PT value measured by these specific reagents can predict apixaban-associated anticoagulant activity, although there is significant interpatient variability.

3D optical coherence tomography: new insights into the process of optimal rewiring of side branches during bifurcational stenting.

AIMS: We describe three-dimensional optical coherence tomography (3D-OCT) guided bifurcation stenting and the clinical utility of 3D-OCT. METHODS AND RESULTS: Twenty-two consecutive patients who underwent OCT examination to confirm the recrossing position after stent implantation in a bifurcation lesion were enrolled. Frequency domain OCT images were obtained to check the recrossing position and 3D reconstructions were performed off-line. The recrossing position was clearly visualised in 18/22 (81.8%) cases. In 13 cases, serial 3D-OCT could be assessed both before and after final kissing balloon post-dilation (FKBD). We divided these cases into two groups according to the presence of the link between hoops at the carina: free carina type (n=7) and connecting to carina type (n=6). All free carina types complied with the distal rewiring. The percentage of incomplete stent apposition (%ISA) of free carina type at the bifurcation segment after FKBD was significantly smaller than that of the connecting to carina type (0.7±0.9% vs. 12.2±6.5%, p=0.0074). CONCLUSIONS: 3D-OCT confirmation of the recrossing into the jailed side branch is feasible during PCI and may help to achieve distal rewiring and favourable stent positioning against the side branch ostium, leading to reduction in ISA and potentially better clinical outcomes.

Serial three-dimensional optical coherence tomography assessment of strut coverage and intraluminal structures after drug-eluting stent implantation.

Understanding of intraluminal structure and distribution of uncovered struts after drug-eluting stent implantation are limited by only 2-dimensional (2D) optical coherence tomography (OCT) images. We compared tissue coverage with 3-dimensional (3D) OCT and 2D quantitative analyses, and changes in intraluminal structure immediately after (baseline) everolimus-eluting stent (EES) implantation and at follow-up. The 2D analyses of uncovered struts ratio and tissue coverage thickness at a 0.5-mm interval were compared to 3D-OCT images and visually classified for the degree of tissue coverage. The difference in tissue coverage at baseline and follow-up after EES implantation was evaluated with tissue coverage scores (TCS) calculated by the 3D-OCT classification (Grade 0-3). 3D-OCT classifications were negatively correlated with uncovered-to-total struts (r = -0.864, P < 0.001) and positively correlated with tissue coverage thickness (r = 0.905, P < 0.001). Follow-up TCS was greater than baseline TCS (0.2 ± 0.4 vs. 1.4 ± 0.5, P < 0.001). Moreover, changes in intraluminal structures and longitudinal distribution of uncovered struts were assessed. Incomplete stent appositions, in-stent dissections, and thrombi were decreased at follow-up, indicating progressive arterial healing. The distribution of uncovered-to-total struts could be assessed by 3D-OCT, which was related to 2D analysis. Significant correlations between 3D-OCT classifications and quantitative analyses were shown. The classification and visual assessment of intraluminal structures by 3D-OCT were useful in evaluating arterial healing after EES implantation.

Tongue muscle-derived stem cells express connexin 43 and improve cardiac remodeling and survival after myocardial infarction in mice.

BACKGROUND: Cell transplantation therapy for heart failure is hindered by poor differentiation into cardiomyocytes and arrhythmias caused by the poor expression of connexin 43 (Cx43). A new stem cell source for cardiac regeneration is needed. METHODS AND RESULTS: Tongue muscle-derived Sca-1(+) cells (TDSCs) were isolated from normal and green fluorescence protein (GFP)-transgenic mouse tongues using surface antigen Sca-1. Cardiomyogenic differentiation was confirmed by measuring the calcium transient and the expression of cardiac-specific genes. The formation of gap junctions was confirmed by the expression of Cx43 and the dye transfer method. The contraction of regenerated cells was demonstrated by the calcium transients. GFP mouse-derived TDSCs were transplanted into hearts in a model of acute myocardial infarction. Three months after transplantation, LV remodeling was attenuated and the survival rate was improved compared with the control group. CONCLUSIONS: TDSCs form gap junctions and improve cardiac function and long-term survival after myocardial infarction.