小林 欣夫

BACKGROUND: The heart responds to hemodynamic overload through cardiac hypertrophy and activation of the fetal gene program. However, these changes have not been thoroughly examined in individual cardiomyocytes, and the relation between cardiomyocyte size and fetal gene expression remains elusive. We established a method of high-throughput single-molecule RNA imaging analysis of in vivo cardiomyocytes and determined spatial and temporal changes during the development of heart failure. METHODS AND RESULTS: We applied three novel single-cell analysis methods, namely, single-cell quantitative PCR (sc-qPCR), single-cell RNA sequencing (scRNA-seq), and single-molecule fluorescence in situ hybridization (smFISH). Isolated cardiomyocytes and cross sections from pressure overloaded murine hearts after transverse aortic constriction (TAC) were analyzed at an early hypertrophy stage (2 weeks, TAC2W) and at a late heart failure stage (8 weeks, TAC8W). Expression of myosin heavy chain β (Myh7), a representative fetal gene, was induced in some cardiomyocytes in TAC2W hearts and in more cardiomyocytes in TAC8W hearts. Expression levels of Myh7 varied considerably among cardiomyocytes. Myh7-expressing cardiomyocytes were significantly more abundant in the middle layer, compared with the inner or outer layers of TAC2W hearts, while such spatial differences were not observed in TAC8W hearts. Expression levels of Myh7 were inversely correlated with cardiomyocyte size and expression levels of mitochondria-related genes. CONCLUSIONS: We developed a new image-analysis pipeline to allow automated and unbiased quantification of gene expression at the single-cell level and determined the spatial and temporal regulation of heterogenous Myh7 expression in cardiomyocytes after pressure overload.

Significant recurrence of atrial tachyarrhythmias are observed after the surgical Cox Maze procedure (CMP). We retrospectively enrolled 11 consecutive patients who had atrial tachyarrhythmias (ATAs) that recurred after a biatrial CMP and underwent catheter ablation. Information including the site of any incomplete lesions and the etiology of the clinical ATAs was shared with the surgical team as feedback. In a total of 11 patients, 12 clinical ATAs were identified. They consisted of 2 atrial fibrillations and 10 atrial tachycardias (ATs). In 6 patients, the CMP was performed after the beginning of this investigation. In a total of 10 ATs, we diagnosed 5 mitral annular flutters, 2 roof-dependent flutters, 1 pulmonary vein (PV)-reentrant AT, and 1 localized reentrant AT. A total of 6 patients had reconnected perimitral block lines. PV reconnections were observed in 3 and posterior wall (PW) residual conduction was also observed in 3 cases. However, no residual conduction of the pulmonary vein isolation (PVI) and only 1 residual conduction of the PW were observed in 5 patients who underwent their index surgery after the beginning of this investigation. This fact may implicate that sharing the information from the electrophysiological study of postsurgical ATAs with the surgical team may contribute to the refinement of the CMP in each facility. <Learning objective: Reconduction of the surgical lesion is the major etiology of recurrence of atrial tachyarrhythmias after the surgical Cox Maze procedure. Although perimitral block line seemed to be the most frequent reconduction site, our study suggested that durable lesion of the PVI and the PW isolation could be achieved by improving surgical techniques by feedback from the electrophysiological team to the surgical team.>.

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570 s, mean 89 ± 98 s). IV nicorandil decreased systolic blood pressure by 32 ± 16 mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and a decrease in blood pressure are the major limitations of this method.

Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.

BACKGROUND: Patient-reported outcomes of implantable cardioverter defibrillator (ICD), such as those with shock anxiety, have emerged as important endpoints that are related to quality of life (QOL), but they have not been well studied in a sample of the Japanese population. Therefore, we prospectively examined changes in shock anxiety in a large sample of Japanese patients with an ICD. METHODS: We recruited 214 consecutive patients with an ICD who visited the outpatient clinic. At registration and 12 months later, all patients completed the Florida Shock Anxiety Scale (FSAS) questionnaire to allow us to examine changes in shock anxiety over the course of the first year after registration. RESULTS: During the 12-month follow-up period, 10.5% of the patients received ICD shock therapy. Female sex, secondary prevention, and experience of ICD shock therapy were associated with high FSAS scores at registration. The FSAS scores in both patients with appropriate and inappropriate shock were significantly higher at the 12-month follow-up interval than at registration, and there was no significant difference in the extent of changes in FSAS scores (Δ = 5.2 ± 5.1 and Δ = 6.3 ± 9.9, respectively, P = 0.62). CONCLUSIONS: Female sex, secondary prevention, and experience of ICD shock therapy are important risk factors affecting shock anxiety in Japanese patients. Attention should be paid to the after-effects of ICD shock in these patients, regardless of the shock type, with particular attention to women and patients who require secondary prevention.

The PRASFIT-ACS study showed the antiplatelet effect 2–4 h after prasugrel loading. However, there is little information about the antiplatelet effect &lt 2 h after prasugrel loading dose, especially in patients with acute coronary syndrome (ACS). There had not been any comparison between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). Fifty patients with ACS (15 with STEMI and 35 with NSTE-ACS) were enrolled. They received a 20-mg prasugrel loading dose followed by a maintenance dose of 3.75 mg. Platelet reactivity [P2Y12 reaction units (PRU)] was evaluated by the VerifyNow assay at baseline, 30 min, 1, 2, 4, and 6 h, 1 week under prasugrel, and at 1 month after switching to clopidogrel. The primary end point was the change of PRU compared to the baseline. Furthermore, PRU after prasugrel loading between STEMI and NSTE-ACS was compared. A significant reduction in PRU from baseline was observed at ≥2 h after administration of prasugrel. In STEMI patients, a significant reduction in PRU was observed at 4 h after prasugrel loading. STEMI patients had higher PRU compared to NSTE-ACS patients at 2, 4, and 6 h after prasugrel loading. Utilizing &gt 208 PRU as a cutoff value, STEMI patients had a higher prevalence of high on-treatment platelet reactivity at 2–6 h and 1 week after loading. Rapid antiplatelet effect is not achieved by low-dose prasugrel loading in STEMI patients. Platelet inhibition occurs earlier in NSTE-ACS patients, although it takes ≥2 h after loading in the majority of patients.

Treating a patient with heparin-induced thrombocytopenia can be challenging particularly when the patient requires urgent cardiac surgery that uses heparin for anticoagulation. We herein report a case of a 61-year-old man with idiopathic dilated cardiomyopathy associated with heparin-induced thrombocytopenia and who underwent plasma exchange to remove heparin-induced thrombocytopenia antibodies before undergoing left ventricular assist device implantation. The surgery was performed using cardiopulmonary bypass and unfractionated heparin.

Introduction: Cardiac implantable electronic devices (CIEDs) can detect atrial fibrillation (AF) early and accurately. Risk factors for the development of new-onset AF in patients with CIEDs remains uncertain. Methods: Patients with CIEDs who visited Chiba University Hospital between January 2016 and December 2016 were enrolled. We only included patients without single chamber CIEDs or a known history of AF. Results: Of 371 patients with CIEDs, 78 (21.0% median age 61.0 years, 65.5% male) developed new-onset AF. Multivariate analysis demonstrated that independent predictors for the development of new or incident AF were age ≥65 years (odd ratio [OR] 2.76, 95% confidence interval [CI] 1.54–4.96, P = 0.001), diabetes mellitus (OR 2.24, 95% CI 1.20–4.19, P = 0.011), congestive heart failure (OR 1.94, 95% CI 1.06–3.54, P = 0.031), and left atrial volume index &gt 34 ml/m2 (OR 3.51, 95% CI 1.96–6.25, P &lt 0.001). Based on these 4 clinical factors (age ≥ 65, diabetes mellitus, congestive heart failure, left atrial volume index &gt 34 ml/m2) there was a good predictive ability for new AF development (AUC 0.728) and clinically usefulness using decision curve analysis. Conclusions: A substantial number of patients with CIEDs develop new-onset AF. Four clinical factors (age ≥ 65, diabetes mellitus, congestive heart failure, left atrial volume index &gt 34 ml/m2) independently predicted new-onset AF and may provide an approach to clinically useful risk assessment for incident AF.

Purpose: Very few studies have investigated the efficacy of ganglionated plexus ablation during the conventional maze procedure. In this study, we sought to evaluate its additive effect in reducing recurrent atrial fibrillation after concomitant maze surgery. Methods: A retrospective study was conducted of 79 patients who underwent Cox maze IV concomitantly with open-heart surgery with (GP group) or without (Maze group) ganglionated plexus mapping. All active ganglionated plexuses were ablated. The two groups were compared and their follow-up data were analyzed. Results: Active ganglionated plexuses were found in 81% of patients who underwent ganglionated plexus mapping. The rates of freedom from atrial fibrillation at 1 year in the GP and Maze groups were 77 and 75%, respectively. The cumulative freedom from atrial fibrillation at follow-up (27.7 ± 17.3 months) was comparable in the two groups (p = 0.427). A multivariate analysis revealed that persistent atrial fibrillation for more than 90 months was an independent predictor of recurrent atrial fibrillation. Conclusion: Ganglionated plexus ablation with Cox maze IV did not reduce the incidence of recurrent atrial fibrillation in comparison to Maze alone.

Forward Projected Model-based Iterative Reconstruction SoluTion (FIRST) is a new reconstruction technique using CT, which provides successful reconstruction of high-quality CT images, especially in low contrast imaging. To evaluate improvements in the diagnostic accuracy of the detection of abnormal late enhancement (LE) in left-ventricular myocardium (LVM) using 320-slice CT with FIRST, we compared this modality with previous CT methods in patients with non-ischemic cardiomyopathy or a cardiac tumor. This was a retrospective study of 88 patients (56 males 57 ± 15 years) suspected of having non-ischemic myocardial disease or a cardiac tumor. The first 52 consecutive patients (Group 1) underwent 16-slice CT at 140 kV tube voltage and an average tube current of 337 ± 20 mA, and 1.5 T MRI. The next 18 patients (Group 2) underwent 1st generation 320-slice CT at 120 kV tube voltage and an average tube current of 255 ± 106 mA, and 1.5T MRI the remaining 18 patients (Group 3) underwent 2nd generation 320-slice CT with FIRST, at 80 kV tube voltage and a tube current of 800 mA, and 1.5T or 3T MRI. On patient-based analysis, no significant differences were observed between the 3 groups. For segment-based analysis, the specificity and overall accuracy were significantly higher (both P &lt 0.05) in Group 3 than in Group 1. Positive predictive value (PPV) was significantly higher in Group 3 than in Groups 1 and 2. The diagnostic accuracy of LE on CT for detecting myocardial fibrosis determined by late gadolinium-enhanced MRI was improved with the use of 2nd generation 320-slice CT with FIRST, in particular regarding specificity, PPV, and overall accuracy. (Int Heart J 2018 59: 542-549)

To achieve further risk stratification in hypertrophic cardiomyopathy (HCM) patients, we localized and quantified layer-specific LVM fibrosis on MRI in HCM patients using regional layer-specific peak longitudinal strain (PLS) and peak circumferential strain (PCS) in LV myocardium (LVM) on speckle tracking transthoracic echocardiography (TTE). A total of 18 HCM patients (14 males 58 ± 17 years) underwent 1.5T-MRI and TTE. PLS and PCS in each layer of the LVM (endocardium, epicardium, and whole-layer myocardium) were calculated for 17 AHA-defined lesions. MRI assessment showed that fibrosis was classified as endocardial, epicardial, or whole-layer (= either or both of these). Regional PLS was smaller in fibrotic endocardial lesions than in non-fibrotic endocardial lesions (P = 0.004). To detect LV endocardial lesions with fibrosis, ROC curves of regional PLS revealed an area under the curve (AUC) of 0.609 and a best cut-off point of 13.5%, with sensitivity of 65.3% and specificity of 54.3%. Regional PLS was also smaller in fibrotic epicardial lesions than in non-fibrotic epicardial lesions (P &lt 0.001). To detect LV epicardial lesions with fibrosis, ROC curves of PLS revealed an AUC of 0.684 and a best cut-off point of 9.5%, with sensitivity of 73.5% and specificity of 55.5%. Using whole-layer myocardium analysis, PLS was smaller in fibrotic lesions than in non-fibrotic lesions (P &lt 0.001). To detect whole-layer LV lesions with fibrosis, ROC curves of regional PLS revealed an AUC of 0.674 and a best cut-off point of 12.5%, with sensitivity of 79.0% and specificity of 50.7%. There were no significant differences in PCS of LV myocardium (endocardium, epicardium, and whole-layer) between fibrotic and non-fibrotic lesions. Quantitative regional PLS but not PCS in LV endocardium, epicardium, and whole-layer myocardium provides useful non-invasive information for layer-specific localization of fibrosis in HCM patients.

Aims: Shortening of the atrial-His bundle (AH) interval during the sinus rhythm is occasionally observed after slow pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT). In addition, high-rate atrial pacing is useful for avoiding atrioventricular block. We hypothesized that shortening of the AH interval during slow pathway ablation under high-rate atrial pacing would lead to successful ablation of typical AVNRT. Methods and results: This retrospective study included 37 patients in whom successful ablation of typical AVNRT was performed under atrial pacing. The AH interval was measured immediately before the first radiofrequency (RF) application and immediately after the last RF application, prior to the first induction. Twenty-five of 37 patients achieved procedural success at the first induction (i.e. successful group). No patients developed a prolonged AH interval or atrioventricular block. The AH interval was shortened by an average of 14.6 ± 7.7 and 1.8 ± 1.2 ms in the successful and other patient groups, respectively (P < 0.01). An AH interval decrease of > 10 ms was observed in 23 of 27 (85%) patients in the successful group, whereas all other patients had an AH interval decrease of < 5 ms. Conclusion: Shortening of the AH interval during high-rate atrial pacing is a predictor of the successful ablation for typical AVNRT.

We used peak longitudinal strain (PLS) on TTE in HCM patients to differentiate LV myocardium (LVM) into the following 4 groups: group 1—no fibrosis or hypertrophy (≥ 13 mm), group 2—no fibrosis but hypertrophy evident, group 3—fibrosis present but without hypertrophy, and group 4—both fibrosis and hypertrophy. Seventeen HCM patients (13 males, 56 ± 16 years) underwent both 1.5 T CMR and TTE. On TTE, PLS (absolute values) for each LVM segment from 17 AHA-defined lesions was calculated. Of 289 LVM lesions, the numbers in each group, 1–4, were 156, 53, 39, and 41, respectively. PLS for LVM segments in group 1 (13.6 ± 6.4%) were significantly greater than those in group 2 (8.5 ± 4.9%, P &lt 0.001), group 3 (10.4 ± 5.0%, P = 0.006), and group 4 (7.1 ± 4.4%, P &lt 0.001). PLS for LVM segments in group 3 was significantly greater than those in group 4 (P = 0.016). However, significant differences in PLS in LVM between groups 2 and 3, and between 2 and 4 were not observed. Using regional PLS, we demonstrate successful differentiation of LVM in HCM patients for group 1 (LVM with zero fibrosis or hypertrophy) from LVM belonging to groups 2–4 and we also demonstrate successful differentiation of LVM with fibrosis present but without hypertrophy from LVM with both fibrosis and hypertrophy. However, it is not possible to differentiate between LVM with no fibrosis but hypertrophy evident and those with fibrosis present but without hypertrophy and also between LVM with no fibrosis but hypertrophy evident and those with both fibrosis and hypertrophy. Our findings have significant implications for the management of HCM patients.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. Although outpatient coronary angiography has been widely performed in current clinical settings, the feasibility and safety of ACh provocation test in outpatient services are unclear. A total of 323 patients, who electively underwent ACh provocation test in hospitalization and outpatient services, were included. Coronary angiography was performed after insertion of a temporary pacing electrode in the right ventricle. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic electrocardiographic changes. Cardiac complications defined as composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, and cardiac tamponade, were evaluated. There were 201 patients (62%) in the hospitalization group and 122 patients (38%) in the outpatient group. The incidence of positive ACh provocation test was similar between the 2 groups (47 vs. 54%, p = 0.21). Coronary angiography in the outpatient group was performed through the radial artery, mostly (98%) with a 4 F sheath. Venous access site was not significantly different between the 2 groups, and the sheath size was 5 F in all cases. There were 2 cases (1.0%) of cardiac complications in the hospitalization group, whereas 1 case (0.8%), which led to unexpected hospitalization, occurred in the outpatient group. In conclusion, intracoronary ACh provocation test for the diagnosis of vasospastic angina in outpatient services was feasible and safe in selected patients.

Background: Cardiovascular surgery is one of the highest risk procedures in the field of surgery. Preoperative assessment of endothelial function has been reported as useful for predicting postoperative adverse events (AEs). The aim of this study was to investigate the relationship between endothelial function assessed by reactive hyperemia index (RHI) and AEs after cardiovascular surgery. Methods and Results: A prospective observational study of 197 patients who underwent cardiovascular surgery was conducted. RHI was measured before the surgery. The primary endpoint was a composite of postoperative death, reoperation, stroke, newly required dialysis, deep sternum infection, and prolonged ventilation within 30 days. The secondary endpoint was new-onset atrial fibrillation (AF) within 30 days. Following cardiovascular surgery, 19 patients (9.6%) had AEs. New-onset AF was documented in 42 (25.9%) of 162 patients without a prior history of AF. In the receiver-operating characteristic curve analysis, RHI significantly predicted AEs (area under the curve [AUC] 0.67, best cutoff value 1.64, P=0.03), whereas RHI did not predict new-onset AF (AUC 0.53, P=0.93). Patients with RHI ≤1.64 had more AEs than those with RHI &gt 1.64 (16.3% vs. 4.5%, P=0.005). Multiple logistic regression analysis showed the number of surgical procedures and RHI ≤1.64 as significant predictors of AEs. Conclusions: Preoperative endothelial dysfunction assessed by RHI was associated with postoperative AEs in patients with cardiovascular surgery.

Augmentation index (AIx) and pulse pressure (PP) amplification can be determined by the SphygmoCor XCEL device in an operator-independent manner. This study aimed to examine its validity against invasive measurements. Simultaneous recordings of central aortic pressure waveforms were performed with oscillometric and high-fidelity invasive methods in 35 patients who underwent coronary arteriography. Brachial blood pressure was also recorded using the two methods. AIx for the aortic pressure waveform was defined as the ratio of augmentation pressure to PP. PP amplification was defined as the ratio of brachial PP to aortic PP. The differences between the invasive and oscillometric measurements were-7.7±12.7% for AIx and 0.17±0.14 for PP amplification (mean±s.d.). Strong correlations between the invasive and oscillometric measurements were found in both indices (AIx: R=0.75 PP amplification: R=0.80 both P&lt 0.001). The Bland-Altman plot showed a proportional bias of PP amplification, but not of AIx (AIx: R=-0.21, P=0.23 PP amplification: R=-0.61 P&lt 0.001). In conclusion, estimated AIx may be reliable considering the high correlation between the invasive and noninvasive values and the lack of proportional bias against invasive assessment. However, a substantial underestimation and a large scatter of estimated AIx were also observed. Further studies using the device to investigate associations with target organ damage or prognoses are needed to clarify its clinical validity.

Objective: To investigate the relationship between 1-h post-load plasma glucose, measured during an oral glucose tolerance test, and arterial stiffness, determined by brachial–ankle pulse-wave velocity, in normotensive subjects with normal glucose tolerance. Methods: Study subjects were non-industrial workers aged 25–55 years (n = 8381) who underwent a regular health check-up every 5 years. We included only normotensive subjects with normal glucose tolerance based on the American Diabetes Association criteria. Subjects taking medication and having an abnormal ankle–brachial index (⩽1.0 or ⩾1.3) were excluded. The final sample comprised 4970 participants (mean age: 38.8 ± 9.4 years women: n = 2048). Results: 1-h post-load plasma glucose correlated with brachial–ankle pulse-wave velocity in men (β = 0.04, p = 0.01), but not women (β = –0.03, p = 0.13) in multivariate linear regression analysis. We found a significant interaction between 1-h post-load plasma glucose and age in men (p = 0.04) therefore, a subgroup analysis was performed in each 5-year age group. The correlation between 1-h post-load plasma glucose and brachial–ankle pulse-wave velocity was significant in the 55-year-old age group (β = 0.12, p = 0.01) and neared significant in 45-year-old (β = 0.08, p = 0.07) and 50-year-old (β = 0.09, p = 0.07) age groups. Conclusion: Elevated 1-h post-load plasma glucose levels were associated with arterial stiffness in normotensive, middle-aged men with normal glucose tolerance.

Background The aim of this study was to investigate microvascular function in patients with valvular heart disease (VHD), which causes chronic left ventricular volume and/or pressure overload, therefore change in coronary microvascular hemodynamics. Patients and methods We prospectively enrolled 30 patients with VHD considered for surgery (10 aortic stenosis, 12 aortic regurgitation, and eight mitral regurgitation) and 30 controls. Intracoronary physiological assessments were performed in the unobstructed left anterior descending artery using a pressure-temperature sensor guidewire at rest and hyperemia. Results The index of microcirculatory resistance (IMR) was similar between the two groups (16.2 ± 6.5 vs. 16.2± 8.5, P=0.997), whereas coronary flow reserve (CFR) was lower in the VHD group compared with the controls (3.2 ± 1.4 vs. 4.3± 1.7, P=0.005). Resting and hyperemic coronary distal pressure, and hyperemic mean transit time were similar between VHD and controls, whereas resting mean transit time was significantly shorter (0.70±0.29 vs. 0.89± 0.39, P=0.035) and baseline resting microvascular resistance was significantly lower in the VHD group compared with the controls (58.1± 25.4 vs. 78.1± 36.7, P=0.011). Patients with aortic stenosis showed numerically higher IMR values than aortic regurgitation, mitral regurgitation, and controls, although this was not statistically significant (20.4 ± 6.9, P=0.14). CFR was significantly correlated with log highsensitivity cardiac troponin T levels in patients with VHD (r=-0.523, P=0.004). Conclusion CFR was reduced in patients with VHD compared with controls, despite similar microvascular function as assessed by IMR. This appeared to be mainly because of an increased resting coronary flow accompanied by a decreased resting coronary microvascular resistance rather than microvascular disease.

Background: Atrial fibrillation (AF) is the most common arrhythmia in the ageing population in East Asia. Silent cerebral infarction (SCI) is defined as cerebral infarction in the absence of corresponding clinical symptoms, and is a highly prevalent and morbid condition in AF. SCI is increasingly being recognized as a risk factor for future stroke, which can lead to cognitive decline or dementia. The latter is an increasingly common health problem in East Asia. Methods and Results: We conducted a meta-analysis to compare the association of AF and SCI between East Asian and non-Asian patients. AF was associated with SCI in patients with no symptomatic stroke history (relative risk [RR], 2.24 95% CI: 1.26–3.99, I2=83% P=0.006) although the prevalence varied widely between studies (P for heterogeneity&lt 0.001). In non-Asian patients, the prevalence of SCI in AF is higher than that in controls (RR, 1.85 95% CI: 1.65–2.08, I2=17% P&lt 0.001). There was no significant racial difference between Asian and non-Asian studies (P=0.53). Conclusions: In East Asia, AF was significantly associated with SCI and no racial difference was seen between East Asian and non-Asian patients. The present findings offer clinicians new insights into the association between AF and SCI.