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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

99mTc-pyrophosphate (99mTc-PYP) uptake in the skeletal muscles is minimal in patients with transthyretin cardiac amyloidosis (ATTR-CA) when assessed qualitatively and quantitatively. We previously demonstrated moderate- to high-grade 99mTc-PYP uptake in the subcutaneous abdominal fat of some patients with ATTR-CA and showed that this abnormal finding could reflect the regional amyloid burden of this tissue. We aimed to investigate the frequency of 99mTc-PYP uptake in skeletal trunk muscles of patients with ATTR-CA.Chest- and abdomen-centered 99mTc-PYP scintigraphy images were obtained 2 hours after IV injections of the tracer (20 mCi) in 36 patients with ATTR-CA. The frequency of 99mTc-PYP uptake in the following 11 skeletal trunk muscles was investigated: pectoralis major, deltoid, subscapularis, infraspinatus, trapezius, latissimus dorsi, erector spinae, psoas major, abdominal oblique, rectus abdominis, and the gluteus muscles.Ten of the 11 muscles were involved in patients with the highest number of 99mTc-PYP uptake in the skeletal trunk muscles examined, whereas no muscle was involved in a patient with the least uptake. The muscle with the highest rate of 99mTc-PYP uptake, observed in 34 of 36 patients (94.4%), was the abdominal oblique. No tracer uptake was observed in the psoas major. The frequency of radiotracer uptake in the remaining examined muscles was between those of abdominal oblique and psoas major muscles.Radiotracer uptake was often detectable in some skeletal trunk muscles of ATTR-CA, although the muscles of patients examined and the skeletal trunk muscles of 1 patient showed heterogeneity in the uptake of 99mTc-PYP.

Background Tolvaptan (TLV) is effective for acute heart failure (HF) with congestion, but its long-term administration in patients with chronic HF (CHF) remains controversial. Moreover, the cost-effectiveness of TLV for CHF treatment has not yet been investigated. Thus, we sought to validate the cost-effectiveness of TLV for CHF treatment in Japan. Methods A Markov model was developed to compare total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) between long-term TLV strategy and the standard strategy using furosemide for CHF. The target population included 75-year-old patients with CHF. The effectiveness of the TLV strategy for CHF treatment was determined based on a systematic review and meta-analysis. We used a 10-year horizon, with sensitivity analyses for significant variables and a scenario analysis for patients with CHF receiving high-dose furosemide (≥60 mg per day). Results In the base case analysis, the total cost of the long-term TLV strategy was higher than that of the standard strategy (\3,243,779 vs. \1,179,964). The total QALYs of the long-term TLV strategy were lower than those of the standard strategy (4.52 vs 4.59). Thus, a standard TLV prescription for CHF treatment has no clinical or economic benefit. In the scenario analysis (i.e. in patients with CHF receiving high-dose furosemide), the long-term TLV strategy was more effective (total QALYs, 5.10 vs. 4.41) but more expensive (total costs, \3,540,558 vs. \1,272,208) than the standard strategy. The ICER of the TLV strategy against the standard strategy (¥3,289,579/QALY) was below the willingness-to-pay of \5,000,000, which suggests that the long-term TLV strategy is cost-effective relative to the standard strategy in patients with CHF receiving high-dose furosemide. Conclusions Long-term TLV administration did not provide a clear benefit for all patients with CHF. However, this treatment strategy may be a cost-effective therapeutic option for patients who require high-dose furosemide.

Aims This study aimed to elucidate the long‐term effect of cibenzoline therapy on cardiovascular complications and prognosis in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods and results Eighty‐eight patients with HOCM were treated with cibenzoline (Group A), and 41 patients did not receive cibenzoline (Group B). The changes in left ventricular (LV) remodelling, incidences of cardiovascular complications and deaths, were examined. The mean follow‐up period was 15.8 ± 5.6 years in Group A and 17.8 ± 7.2 years in Group B. In Group A, the LV pressure gradient (LVPG) decreased immediately after treatment, and the reduction was maintained throughout the study. In Group B, the LVPG decreased gradually according to the deterioration of LV function. LV reverse remodelling was confirmed in Group A, and LV remodelling advanced in Group B. In Group A, the incidence of each cardiovascular complication was

In a patient with variant angina of the proximal left anterior descending coronary artery, myocardial ischemia changed the QRS-ST-T configurations without J-waves into those resembling “lambda” waves at maximal ST-segment elevation, and couplets or triplets of supraventricular extrasystole (SVE) changed the ischemia-induced “lambda” waves into QRS-ST-T configurations resembling a “tombstone” morphology or “monophasic QRS-ST complex.” At the resolution phase of coronary spasm, the QRS-ST-T configurations returned to those without J-waves and were changed by SVE into “lambda” waves. Interestingly, neither ischemia- nor SVE-induced “lambda” waves or SVE-induced “tombstone” morphology or “monophasic QRS-ST complex” were complicated by ventricular tachyarrhythmia.

Aims This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium‐201 myocardial scintigraphy. Methods and results Forty‐eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the ‘mean count change’ (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium‐201 uptake (TU), MCC (%) was calculated using the following formula: (last TU − initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow‐up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P

It is unclear whether afterload mismatch occurs during the initial stage of essential hypertension (EHT). Additionally, critical left ventricular hypertrophy (LVH) between preserved and reduced systolic functions in hypertension is also unclear. Thus, we aimed to clarify these points.Forty-five normal control subjects (NCS) and 140 EHT patients participated. EHT patients were subdivided into three groups: group I, without LVH (n = 37); group II, with LVH (n = 80); and group III, with LVH and LV heart failure (LVHF) (n = 23). Routine electrocardiographic and echocardiographic parameters, V5R/V6R ratio, relative wall thickness (RWT), LV mass (LVM) index, and peak systolic wall stress (PSWS) were measured.In group I, LV systolic functions were preserved despite the increase of PSWS. In group II, LVH advanced, but LV systolic functions remained normal. A negative T-wave was observed in 69% of group II and 100% of group III. A significant correlation between RWT and LVM index was seen in NCS and groups I and II (rAfterload mismatch did not occur in group I, but it was observed in group III due to the exhaustion of preload reserve.

Background This study aimed to evaluate the combined diagnostic performance of coronary artery stenosis-subtended myocardial volume (Vsub) and myocardial blood flow (MBFsub) on computed tomography (CT) for detecting obstructive coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) and fractional flow reserve (FFR). Methods Thirty-nine patients who underwent coronary CT angiography (CTA) and stress dynamic myocardial CT perfusion (CTP) prior to ICA were enrolled. Obstructive CAD was defined as severe (≥70%) or moderate (30–69%) stenosis with FFR ≤0.8 on ICA. The Vsub was semi-automatically calculated from coronary CTA data using Voronoi diagram-based myocardial segmentation. The standard CT-MBF based on the 17-segment model was calculated using dynamic stress CTP data and deconvolution analysis. The CT-MBFsub was automatically analyzed by integrating the CT-MBF and Voronoi diagram-based myocardial segmentation analyses. The diagnostic performance of combined CT-MBFsub and Vsub assessment was determined using receiver operating characteristic analysis and compared with standard CT-MBF and CT-MBFsub. Results Of 117 vessels in 39 patients, 72 vessels were suspected of significant stenosis on CTA and 33 vessels had obstructive CAD on ICA and FFR. The sensitivity and specificity for identifying obstructive CAD were 67% and 82% for standard CT-MBF, 70% and 77% for CT-MBFsub, and 85% and 82% for combined CT-MBFsub and Vsub assessment. The area under the receiver operating characteristic curve of the combined CT-MBFsub and Vsub assessment was significantly higher than those of standard CT-MBF and CT-MBFsub (0.89 vs. 0.75, 0.77; p Conclusions The Vsub may aid in increasing the diagnostic performance of CT-MBFsub for detecting obstructive CAD.

BACKGROUNDS The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, the visual assessment of RASP is inconsistent, and the quantitative assessment of RASP is time-consuming. This study aimed to compare assessments of RASP for the identification of CA with conventional assessments and investigate their reproducibility and relevance on the assessments. METHODS Forty patients with biopsy-proven CA were compared with 80 hypertrophied patients matched for mean LV wall thickness. We compared the discriminative abilities of three assessments of RASP to identify CA (visual, quantitative, and semiquantitative). Nine patterns of semiquantitative RASP were investigated; finally, it was defined as "reduction of LS" (≥ -10%) in ≥5 (of 6) basal segments, relative to "preserved LS" (

PURPOSE: Reduction in methylenetetrahydrofolate reductase (MTHFR) activity due to genetic variations in the MTHFR gene has been controversially implicated in subfertility in human in vitro fertilization. However, there is no direct gene-knockdown study of embryonic MTHFR to assess its involvement in mammalian preimplantation development. The purpose of this study is to investigate expression profiles and functional roles of MTHFR in bovine preimplantation development. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) and analysis of publicly available RNA-seq data were performed to reveal expression levels of MTHFR during bovine preimplantation development. We knocked down MTHFR by siRNA-mediated RNA interference from the 8- to 16-cell stage and assessed the effects on preimplantation development. RESULTS: The RT-qPCR analysis showed relatively high MTHFR expression at the GV oocyte stage, which was decreased toward the 8- to 16-cell stage and then slightly restored at the blastocyst stage. Public data–based analysis also showed the similar pattern of expression with substantial embryonic expression at the blastocyst stage. MTHFR knockdown reduced the blastocyst rate (P

The slow flow phenomenon is a critical complication during percutaneous coronary intervention (PCI) that leads to poor outcomes. We aimed to evaluate the mechanisms underlying the slow flow phenomenon using intravascular ultrasound (IVUS). We retrospectively analyzed IVUS data from 62 lesions in 58 consecutive patients who experienced the slow flow phenomenon during PCI. IVUS was performed immediately after the development of the slow flow phenomenon to assess its cause. No IVUS-based evidence of mechanical obstruction was categorized as distal embolization. Distal embolization was observed in 46 lesions (74%). The slow flow phenomenon occurred in all these lesions after stent implantation. In addition to distal embolization, three different mechanisms underlying the induction of the slow flow phenomenon due to mechanical obstructions (16 lesions, 26%) were detected on IVUS, namely, medial dissection/hematoma (6 lesions), intimal flap (6 lesions), and thrombus obstruction (4 lesions). Most mechanical obstructions (13 lesions, 81%) could not be identified by angiography alone. In 15/16 lesions (94%) with mechanical obstruction, deteriorated flow improved immediately after balloon dilatation or bail-out stent implantation, although intracoronary vasodilator administration could not reestablish coronary flow. The frequency of mechanical obstruction as the cause of the slow flow phenomenon was relatively high. Given the difficulty in angiographical differentiation, IVUS-guided management of slow flow may be a useful strategy.

Background Cardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients. Methods We retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or 99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). Results Fifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0–4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88). Conclusions We developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.

Rationale: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited. Patient concerns: An 85-year-old Japanese woman with active PMR developed first syncope. Diagnosis: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP. Interventions: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective. Outcomes: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia. Lessons: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Aims Cardiac amyloidosis (CA) is an infiltrative myocardial disease that occasionally mimics hypertrophic cardiomyopathy (HCM). The aim of this study is to investigate the discriminatory ability of visual assessment of left atrial (LA) function between CA and HCM on echocardiography. Methods and results In total, 93 patients with cardiac magnetic resonance imaging (CMR)‐confirmed HCM and 34 with cardiac biopsy‐confirmed CA were retrospectively assessed. LA dilatation was assessed via echocardiography in an apical four‐chamber view. Visual assessment was performed to identify LA dilatation grade (preserved = 1, abnormal = 2, and restricted = 3) based on the extent of outward expansion in the LA reservoir phase. Regarding the reproducibility of visually assessing LA dilatation grade, the kappa values between intra‐ and inter‐observer measurements were 0.82 and 0.70, respectively. Of 127 participants, 57 (45%), 42 (33%), and 28 (22%) presented with LA dilatation Grades 1, 2, and 3, respectively. All 57 patients with preserved LA dilatation (Grade 1) had HCM, and 20 of 28 patients (71%) with restricted LA dilatation (Grade 3) presented with CA. Patients with CA had a higher LA dilatation grade than those with HCM (P

The purpose of this study was to evaluate the feasibility of the stenosis-related quantitative perfusion ratio (QPR) for detecting hemodynamically significant coronary artery disease (CAD). Twenty-seven patients were retrospectively enrolled. All patients underwent dynamic myocardial computed tomography perfusion (CTP) and coronary computed tomography angiography (CTA) before invasive coronary angiography (ICA) measuring the fractional flow reserve (FFR). Coronary lesions with FFR ≤ 0.8 were defined as hemodynamically significant CAD. The myocardial blood flow (MBF) was calculated using dynamic CTP data, and CT-QPR was calculated as the CT-MBF relative to the reference CT-MBF. The stenosis-related CT-MBF and QPR were calculated using Voronoi diagram-based myocardial segmentation from coronary CTA data. The relationships between FFR and stenosis-related CT-MBF or QPR and the diagnostic performance of the stenosis-related CT-MBF and QPR were evaluated. Of 81 vessels, FFR was measured in 39 vessels, and 20 vessels (51%) in 15 patients were diagnosed as hemodynamically significant CAD. The stenosis-related CT-QPR showed better correlation (r = 0.70, p r = 0.56, p p

Background The relationship between shot-to-shot sampling rates for dynamic myocardial computed tomography perfusion (CTP) and robustness of CTP-derived myocardial blood flow (CT-MBF) is debatable. We retrospectively investigated the influence of a reduced sampling rate for dynamic CTP on CT-MBF computation and diagnostic performance for detecting myocardial perfusion abnormalities. Methods Pharmacological stress dynamic whole-heart CTP was performed in 120 patients suspected with coronary artery disease. Dynamic CTP data were obtained for 30 continuous heartbeats during the R-peak to R-peak (1RR) interval on electrocardiography. Three additional datasets were created with sub-sampling acquisitions every 2, 3, and 4 heartbeats from the original dataset as interval times of 2RR, 3RR, and 4RR, respectively. CT-MBF was calculated using deconvolution analysis and determined as the mean value of the whole heart (global CT-MBF) and using the 16-segment model (segmental CT-MBF). The diagnostic performance of segmental CT-MBF for detecting perfusion abnormalities was compared to that of cardiac magnetic resonance imaging as the gold standard in 32 of 120 patients. These results were compared among the four CTP datasets. Results Global CT-MBFs for 1RR, 2RR, 3RR, and 4RR sampling were 1.57 ± 0.34, 1.54 ± 0.36, 1.51 ± 0.37, and 1.41 ± 0.33 mL/g/min, respectively. Areas under the receiver operating characteristic curves of segmental CT-MBF for 1RR, 2RR, 3RR, and 4RR sampling were 0.84, 0.83, 0.79, and 0.76, respectively (1RR versus [vs.] 2RR, non-significant; 1RR vs. 3RR or 4RR, p Conclusion CT-MBF with 2RR sampling has similar performance with regard to quantification and detecting myocardial perfusion abnormalities as that with 1RR sampling.

BACKGROUND This study evaluated the diagnostic capability of on-site coronary computed tomography-derived computational fractional flow reserve (CT-FFR) determinations for detecting coronary artery disease (CAD), as assessed by invasive fractional flow reserve (FFR).Methods and Results:Seventy-four patients with coronary artery calcium scores

This study aimed to evaluate the incremental diagnostic value of dynamic myocardial computed tomography (CT) perfusion (CTP) imaging for detecting obstructive coronary artery disease (CAD) in comparison with coronary CT angiography (CTA).Thirty-eight patients who had undergone coronary CTA and pharmacological stress dynamic CTP before invasive coronary angiography (ICA) were selected retrospectively. Using ICA, obstructive CAD was defined as the presence of severe (≥70%) or moderate (50-69%) stenosis with fractional flow reserve (FFR)0.75. For CT evaluations, coronary vessels with any stenosis ≥50%, ≥70% or unassessable lesions were considered significantly stenotic. Dynamic CTP was assessed quantitatively using CT-derived myocardial blood flow (CT-MBF). Receiver operating characteristic (ROC) curve analysis determined the cut-off value of CT-MBF for identifying obstructive CAD. The diagnostic performances of CTA alone and integrated CTA and CTP assessments for detecting obstructive CAD were compared.Using ICA and FFR, 24 of 114 vessels had obstructive CAD. The cut-off value of CT-MBF for detecting obstructive CAD was 1.26mL/g/min. The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) at the vessel level were 96%, 57%, 37%, and 98% for CTA, and 83%, 93%, 77%, and 95% for integrated CTA and CTP assessment using cut-off 50% stenosis on CTA, respectively. The sensitivity, specificity, and PPV and NPV at the vessel level were 79%, 69%, 40%, and 93% for CTA, and 71%, 97%, 85%, and 93% for integrated CTA and CTP assessment using cut-off 70% stenosis on CTA, respectively. The area under the ROC curve for CTA and CTP was significantly higher than that for CTA alone (0.96 vs. 0.84, p0.05).Stress dynamic myocardial CTP is feasible to detect hemodynamically obstructive CAD in patients with high pre-test likelihood and helps for improving diagnostic performance in comparison with coronary CTA alone.

Computed tomography (CT)-derived three-dimensional maximum principal strain (MP-strain) can provide incremental value to coronary CT angiography for cardiac dysfunction assessment with high diagnostic performance in patients with myocardial infarction. Global longitudinal strain (GLS) measured using two-dimensional speckle tracking echocardiography (2D-STE) is more sensitive than left ventricular ejection fraction (LVEF) for detecting early myocardial dysfunction. We aimed to compare CT-derived MP-strain with each of 2D-STE-derived strains (i.e., longitudinal, circumferential, and radial strains), and identify the major determinants of CT-derived MP-strain among 2D-STE-derived strains. We studied 51 patients who underwent cardiac CT and echocardiography. CT images were reconstructed at every 5% (0-95%) of the RR interval. A dedicated workstation was used to analyze CT-derived MP-strain on the 16-segment model. We calculated CT-derived global MP-strain with all the 16 segments on a per patient basis. Pearson's test was used to assess correlations between CT-derived MP-strain and STE-strain at global and segmental levels. The intra-class correlation coefficient for interobserver agreement for CT-derived global MP-strain was 0.98 (95% confidence interval 0.96-0.99). The low-CT-derived global MP-strain group (≤ 0.43) had more patients with LV dysfunction than the high-CT-derived global MP-strain group ( 0.43). CT-derived global MP-strain was associated with STE-GLS (r = 0.738, P 0.001), global circumferential strain (r = 0.646, P 0.001), and global radial strain (r = 0.432, P = 0.001). In multivariate analysis, STE-GLS had the strongest association to CT-derived global MP-strain among three directional STE-strains and LVEF by echocardiography (standardized coefficient = - 0.527, P 0.001). STE-GLS is a major determinant of CT-derived global MP-strain. CT-derived MP-strain may enhance the value of coronary CT angiography by adding functional information to CT-derived LVEF.

Incisional atrial tachycardia (AT) with multiple penetrating points on one surgical incision has not been reported. We present a case of incisional AT following mitral annuloplasty with a superior transseptal approach, in which two reconduction sites were part of the reentrant circuit. Radiofrequency ablation at the reconduction site successfully terminated the tachycardia. A total of four penetrating points were found on the incision line, and radiofrequency ablation at these sites was completed. Detailed mapping with consideration of possible reconduction sites along the incision line should be performed to avoid further instances of AT following open heart surgery.

Contains fulltext : 225829.pdf (Publisher’s version ) (Closed access) We aimed to evaluate the effects of four-dimensional noise reduction filtering using a similarity algorithm (4D-SF) on the image quality and hemodynamic parameter of dynamic myocardial computed tomography perfusion (CTP). Sixty-eight patients who underwent dynamic myocardial CTP for the assessment of coronary artery disease were enrolled. Dynamic CTP was performed using a 320-row CT with low tube voltage scan (80 kVp). Two different datasets of dynamic CTP were reconstructed using iterative reconstruction (IR) alone and a combination of IR and 4D-SF. Qualitative (5-grade scale) and quantitative image quality scores were assessed, and the CT-derived myocardial blood flow (CT-MBF) was quantified. These results were compared between the two different CTP images. The qualitative image quality in CTP images reconstructed with IR and 4D-SF was significantly higher than that with IR alone (noise score: 4.7 vs. 3.4, p < 0.05). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in CTP images reconstructed with IR and 4D-SF were significantly higher than those with IR alone (SNR: 20.6 vs. 9.7; CNR: 7.9 vs. 3.9, respectively; p < 0.05). There was no significant difference in mean CT-MBF between the two sets of CTP images (3.01 vs. 3.03 mL/g/min, p = 0.1081). 4D-SF showed incremental value in improving image quality in combination with IR without altering CT-MBF quantification in dynamic myocardial CTP imaging with a low tube potential.

This study evaluated the characteristics of left ventricular maximum principal strain (LV-MPS) using cardiac CT in subjects with normal LV function. Of 973 subjects who underwent retrospective electrocardiogram-gated cardiac CT using a third-generation dual-source CT without beta-blocker administration, 31 subjects with preserved LV ejection fraction ≥ 55% assessed by echocardiography without coronary artery stenosis and cardiac pathology were retrospectively identified. CT images were reconstructed every 5% (0–95%) of the RR interval. LV-MPS and the time to peak (TTP) were analyzed using the 16-segment model and compared among three levels (base, mid, and apex) and among four regions (anterior, septum, inferior, and lateral) using the Steel–Dwass test. The intra- and inter-observer reproducibilities for LV-MPS were calculated using intraclass correlation coefficients (ICCs). The intra- and inter-observer ICCs (95% confidence interval) for peak LV-MPS were 0.96 (0.94–0.97) and 0.94 (0.92–0.96), respectively. The global peak LV-MPS (median, inter-quantile range) was 0.59 (0.55–0.72). The regional LV-MPS significantly increased in the order of the basal (0.54, 0.49–0.59), mid-LV (0.57, 0.53–0.65), and apex (0.68, 0.60–0.84) (p

Our aim was to evaluate the ability of adenosine triphosphate (ATP)-stress myocardial computed tomography perfusion (CTP) imaging to detect myocardial ischemia in the left anterior descending artery (LAD) territory, and to compare this method with coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE).ATP-stress CTP and CFVR were performed in 50 patients with stable angina pectoris. Myocardial ischemia assessed from CTP imaging was defined as qualitative visual perfusion defects and reduced myocardial blood flow (MBF) based on quantitative assessment. A cut-off value of CFVR of 2.0 was used.The mean CFVR was 1.9 ± 0.6 in ischemic regions by CTP, whereas it was 2.9 ± 0.8 in non-ischemic regions (p 0.001). CTP imaging could accurately predict CFVR2.0 with 84.0% diagnostic accuracy (94.7% sensitivity, 77.4% specificity, 72.0% positive predictive value, and 96.0% negative predictive value). When receiver operating characteristic curve analysis of the MBF data was performed to detect CFVR2.0, the area under the curve was 0.89, and the optimal MBF cut-off value was 1.43 mL/g/min.This study suggests that qualitative and quantitative assessment of ATP-stress CTP exhibits a good correlation with CFVR for evaluation of myocardial ischemia.

PURPOSE Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients. METHODS Seventy-six patients with HCM who underwent echocardiographic and cardiac magnetic resonance imaging were retrospectively enrolled. Twenty-six control subjects were also included. Using speckle tracking echocardiography, LA function was divided into active and passive strain indices based on the timing of the second positive peak of LA strain rate that occurred during LV systole. RESULTS Left atrial strain indices of active and passive function were significantly impaired concomitantly with increased LA volume index in HCM patients compared with controls. During follow-up (2.6 ± 1.7 years), 14 patients with HCM developed cardiac events (heart failure hospitalization or atrial fibrillation). The association of LA active strain with cardiac events was independent of and incremental to clinical and echocardiographic parameters (age, gender, E/e', LV global longitudinal strain, and LA volume index) in sequential models. Cardiac events were more frequent in HCM patients with LA active strain

The Shikoku Rivaroxaban Registry Trial (SRRT) is a retrospective survey of the use of rivaroxaban for stroke prevention in elderly patients in Shikoku, Japan.The SRRT enrolled 1339 patients from 8 hospitals. Patients were divided into two groups according to their age, the extreme elderly group (453 patients aged ≧80 years) and the control group (886 patients aged80 years).In the extreme elderly group, 41.5% of the patients had low body weight (50kg) and 65.1% had abnormal renal function (creatinine clearance50ml/min). The mean CHADSThese results suggest that rivaroxaban is effective and safe in extreme elderly patients with atrial fibrillation.

Bovine preimplantation embryos exhibit dramatic biological changes between before and after the 8-16-cell stage. Here we report a simple lipofection method to transfect siRNA into bovine 8-16-cell stage embryos using zona removal and the well-of-the-well (WOW) culture system. Bovine one-cell embryos produced in vitro were freed from the zona pellucida and cultured up to the 8-16-cell stage in WOW dishes. The 8-16-cell embryos were lipofected with siRNA and the transfection efficiency was assessed at 48 h of transfection. Lipofection with a red fluorescent non-targeting siRNA revealed the importance of zona removal for transfection of siRNA into embryos. Using this method, we knocked down the methionine adenosyltransferase 2A (MAT2A) gene, achieving a significant reduction in MAT2A expression (P < 0.05) concomitant with the marked inhibition of blastocyst development. Our proposed method, tentatively named 'Octo-lipofection', may be useful to analyze gene functions in bovine preimplantation embryos without expensive equipment and skill-intensive techniques.

Background To examine whether the use of one value of natriuretic peptides to define "normal" is appropriate in all individuals, and to assess the influence of sex, age, and other variables on atrial and brain natriuretic peptides (ANP, BNP) levels. Methods and results A total of 1375 apparently healthy people (women:155, men:1220), aged 18–70years were enrolled. Both ANP and BNP levels were higher in women than in men (ANP: 12.50±6.82pg/mL vs 8.18±4.19pg/mL; BNP: 9.85±7.63pg/mL vs 7.03±6.97pg/mL). The subjects were divided into three age groups: group I, 18–30years; group II, 30–50years; group III, 50–70years. First, the influence of age on ANP and BNP levels was examined. In women, both ANP and BNP levels were higher in groups II and III than those in group I. In men, ANP and BNP levels increased with age. Second, sex differences in ANP and BNP levels due to age were examined. ANP level was higher in women than that in men in all age groups. BNP level was higher in women than that in men in groups I and II. Multivariate analysis indicated that both ANP and BNP levels were influenced by age, hemoglobin level, and platelet counts. Conclusion Because ANP and BNP levels in healthy subjects are influenced by sex, age, and hemoglobin levels, the use of a single value to define "normal" in all individuals is not appropriate.

Intraprocedural stent thrombosis (IPST) is a rare complication of percutaneous coronary intervention that leads to poor outcomes; however, the factors contributing to IPST remain largely unknown. Accordingly, we used intravascular ultrasound (IVUS) to examine the lesion characteristics in patients with IPST. We retrospectively analyzed 1,504 consecutive stent-implanted lesions in 1,324 patients (326 with ST-segment elevation myocardial infarction [STEMI], 403 patients with non-ST-segment elevation acute coronary syndrome [NSTE-ACS], and 595 patients with stable angina). Of these, IPST occurred in 5 patients during percutaneous coronary intervention (0.4% per patient; 3 with STEMI, 2 with NSTE-ACS). The IVUS characteristics of plaques that developed IPST were compared with those of controls without the evidence of IPST (non-IPST; n = 15) who were matched by age, gender, lesion location, and clinical presentation (STEMI, NSTE-ACS, or stable angina). All 5 lesions that led to IPST had ruptured plaques with positive remodeling and attenuation. Plaque rupture was also observed in 40% of the non-IPST group. Multiple plaque ruptures in the culprit lesion were more common in the IPST group (80% vs 7%; p0.01). The maximum cavity area was larger in the IPST group than in the non-IPST group having plaque rupture (4.6 mm(2) [interquartile range, 4.3 to 6.5] vs 2.4 mm(2) [1.8 to 2.9]; p0.01). In conclusion, we found using IVUS that multiple plaque ruptures with larger cavities more often evolved into IPST.

BACKGROUND To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling. METHODS AND RESULTS Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB ≥2.5%, n=33) and group L (CK-MB

The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM.Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

BACKGROUND Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P

This study investigated the relationship between the degree of atherosclerotic changes in the descending thoracic aorta (TA) and the coronary artery using angioscopy. Twenty-five consecutive patients undergoing angioscopy of the TA and coronary angiography were enrolled in this study. Participants were divided into three groups according to the angioscopic grading of the TA: white plaque group (W-group), yellow plaque group (Y-group) and intensive yellow, ruptured plaque with ulceration and/or thrombus group (RP-group). The maximum plaque grade, plaque score, number of yellow plaques, frequency of yellow-plaque grades by coronary angioscopy, and SYNTAX score by coronary angiography were evaluated. Brachial-artery pulse wave velocity and high-sensitivity C-reactive protein level tended to be higher in the RP-group than in the other groups, although the differences were not statistically significant. The SYNTAX score was significantly higher in the RP-group than in the W-group (W-group 4.0 ± 3.6 vs. RP-group 17.5 ± 10.0, P = 0.045). In addition, the angioscopic maximum plaque grade, plaque score, and number of yellow plaques in the RP-group were significantly higher than in the W-group (maximum plaque grade W-group 0.8 ± 0.4 vs. RP-group 1.8 ± 0.8, P = 0.026; plaque score W-group 1.0 ± 1.2 vs. RP-group 4.0 ± 1.4, P = 0.014; and number of yellow plaques W-group 1.0 ± 1.2 vs. RP-group 2.5 ± 0.5, P = 0.023). The yellow-plaque grade in the coronary artery was correlated significantly with the plaque grading of TA (P = 0.043). Our study suggests that the angioscopic progression of aortic atherosclerosis is closely associated with vulnerability to and the extent of coronary stenosis, indicating that vulnerability toward atherosclerotic plaque development occurs simultaneously in the coronary tree and systemic arteries. Electronic supplementary material The online version of this article (doi:10.1007/s10554-015-0669-z) contains supplementary material, which is available to authorized users.

We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan–Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82–1.86)]; there were no significant differences in secondary endpoints. Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. Clinicaltrials.gov number: NCT00212017

Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Optical coherence tomography (OCT) provides accurate visualization of coronary artery morphology. The aim of this study was to investigate the relation between FFR and OCT-derived FFR. We retrospectively analyzed 31 lesions (25 left anterior descending arteries, 2 left circumflex arteries, and 4 right coronary arteries) in 31 patients with moderate-to-severe coronary stenosis, who underwent OCT and FFR measurements simultaneously. OCT-derived FFR was calculated by the original algorithm, which was calculated using the following equation based on fluid dynamics: ΔP = FV + SV 2 , where V is the flow velocity, F is the coefficient of pressure loss because of viscous friction (Poiseuille resistance), and S is the coefficient of local pressure loss because of abrupt enhancement (flow separation). Mean values of % diameter stenosis by quantitative coronary angiography and FFR were 55.2 ± 14.0% and 0.70 ± 0.14, respectively. OCT-derived FFR showed a stronger linear correlation with FFR measurements (r = 0.89, p

Background Quantitative assessment of myocardial flow reserve (MFR) by single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is challenging but may facilitate evaluation of multi-vessel coronary artery disease (CAD). Methods We enrolled 153 patients with suspected or known CAD, referred for pharmacological stress MPI. They underwent a 99m Tc-perfusion stress/rest SPECT with an ultrafast cadmium-zinc-telluride (CZT) camera. Dynamic data were acquired and time-activity curves fitted to a 1-tissue compartment analysis with input function. K1 was assigned for stress and rest data. The MFR index (MFR i ) was calculated as K1 stress/K1 at-rest. The findings were validated by invasive coronary angiography in 69 consecutive patients. Results The global MFR i was 1.46 (1.16–1.76), 1.33 (1.12–1.54), and 1.18 (1.01–1.35), for 1-vessel disease (VD), 2-VD, and 3-VD, respectively. In the 3-VD, global MFR i was lower than that in 0-VD (1.63 [1.22–2.04], P i (OR: 119.6 [111.5–127.7], P=0.002). A cut-off value of 1.3 yielded 93.3% sensitivity and 75.9% specificity for diagnosing 3-VD. Fractional flow reserve positively correlated with regional MFR i (r=0.62, P=0.008), and the SYNTAX score correlated negatively with global MFR i (r=0.567, P=0.0003). Conclusion We developed and validated a clinically available method for MFR quantification by dynamic 99m Tc-perfusion SPECT utilizing a CZT camera, which improves the detectability of multi-vessel CAD.

Although saphenous vein grafts (SVGs) are widely used as conduits for coronary artery bypass grafting (CABG), SVG atheroma following CABG remains one of the major concerns. However, the morphological characteristics of old SVGs are not fully understood, especially in patients with stable angina pectoris. We imaged 9 consecutive SVGs in patients with stable angina pectoris using optical coherence tomography and coronary angioscopy. The clinical, optical coherence tomography, and coronary angioscopy characteristics of the SVGs are summarized in the Table. Multimodality imaging observations were performed in 4 SVGs without stenosis (nonculprit) and in 5 SVGs with significant stenosis before percutaneous coronary intervention (culprit). The graft age of the 7 SVGs (old SVGs) was >10 years, and the remaining 2 SVGs (young SVGs) were aged

An impaired myocardial perfusion state after primary angioplasty is a strong predictor of long-term adverse outcomes in patients with STEMI. We assessed the relationship between culprit plaque characteristics and myocardial perfusion state after primary angioplasty in patients with ST-segment elevation myocardial infarction (STEMI).A total of 101 consecutive patients with de novo STEMI were divided into 3 groups according to the state of myocardial perfusion assessed by ST-segment elevation resolution (STR): Group A (complete: STR ≥ 70%, n=26), Group B (partial: STR70% but ≥ 30%, n=55) and Group C (none: STR30%, n=20). We analyzed plaque features by virtual histology intravascular ultrasound (VH-IVUS) and assessed the relationship between culprit plaque characteristics and STR after primary angioplasty.Total plaque volume was significantly higher in Group C than in Groups A and B (146.4 ± 38.0 mm(3)vs. 93.3 ± 29.1 mm(3) and 105.8 ± 31.5 mm(3), p0.001, respectively). Necrotic core (NC) volume was also significantly higher in Group C than in Groups A and B (25.4 ± 8.0m m(3), vs. 11.9 ± 6.3 mm(3) and 17.3 ± 9.7 mm(3), p0.001, respectively). Analysis of receiver-operating characteristic curves revealed that total plaque volume and NC volume had the best diagnostic accuracy of all the VH-IVUS parameters to predict STR30%. The optimal cutoff values (sensitivity/specificity) were 123.4 mm(3) (75.0%/75.3%) for total plaque volume and 20.3mm(3) (75.0%/74.1%) for NC volume.Culprit plaque with large plaque burden and high NC volume is closely associated with poor STR after revascularization.

In recent years, while therapeutic outcome after percutaneous coronary intervention is improving due to the introduction of drug-eluting stent and device development, procedure-related complications including coronary perforation may ineluctably occur though at low-frequency, even if careful manipulations are performed under IVUS guidance. Meanwhile, coronary pseudoaneurysm subsequent to coronary perforation is one of the complications at chronic phase infrequently experienced following percutaneous coronary intervention. To date, the incidence and natural history of pseudoaneurysm following coronary artery perforation remain unclear. We experienced a case with coronary pseudoaneurysm developed 2 weeks after Ellis II-type coronary artery perforation which spontaneously disappeared 4 months later. As the mechanism of disappearance, thrombotic occlusion was confirmed upon intravascular ultrasound.

The relationship between atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) and sleep-disordered breathing (SDB) evaluated using type-3 portable monitoring (PM) is still unknown. We investigated high-risk patients with AF recurrence after initial PVI using the apnea–hypopnea index (AHI) measured by type-3 PM. One hundred twenty-four (85 males; age 62 ± 10 years) AF patients undergoing initial PVI were enrolled: 83, paroxysmal AF; 41, persistent AF. At baseline, all patients were subjected to in-hospital unattended overnight polygraphy using type-3 PM for SDB. During 13 ± 7 months following initial PVI, 47 patients (38 %) experienced AF recurrence. AHI and left atrial volume index (LAVI) were significantly greater in patients with than in those without AF recurrence (AHI P = 0.011; LAVI P

One-carbon metabolism (OCM) can be seen as integrated metabolic pathways centered on the metabolism of two nutritional substances, folate and methionine. Mammalian oocytes and preimplantation embryos express almost all enzymes that participate in OCM, suggesting that they can independently metabolize OCM nutrients. A deficiency or excess of OCM nutrients and their metabolites during in vitro culture affects preimplantation development of mammalian embryos. Recent in vivo studies have demonstrated that specific OCM dietary interventions during the periconceptional (mainly oocyte growth and preimplantation) period can cause epigenetic alterations in DNA of offspring and program the long-term consequences in their health in adulthood. The epigenetic processes are likely to be implicated in the effects of OCM nutrients; however, understanding their effects at the level of specific genes and their implications in assisted reproductive technology will require further investigations.

An 81-year-old woman was referred to our hospital because of dyspnoea. Except for hypertension, her past medical history was uneventful. No history of tuberculosis was documented. However, her husband had developed tuberculosis when he was in his 20s. Moist rales were audible predominantly in the bilateral lower lung fields. Sputum examination did not reveal tuberculous bacilli. Electrocardiography demonstrated T-wave inversion in the II–III, aVF, and V4–V6 leads. A …