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Background The risk of restenosis after intervention is higher in femoropopliteal than in aortoiliac lesions. However, the appropriate endovascular therapy (EVT) for preventing restenosis after intervention for femoropopliteal lesions remains unknown. This study aimed to elucidate the relationship between lesion characteristics and patency after EVT using intravascular ultrasound (IVUS) measurement and to determine the predictors of restenosis on IVUS.Methods and Results:This prospective observational study was performed at 18 Japanese centers. We evaluated the lesion characteristics before and after EVT for femoropopliteal lesion using IVUS. Angiographic or duplex ultrasound follow-up was performed at 1 year after EVT. A total of 263 lesions underwent EVT between December 2016 and December 2017. In total, 20 lesions (8 cases of isolated common femoral artery lesion and 12 cases of restenosis lesion) were excluded, and 243 lesions were enrolled in this study. A total of 181 lesions were treated with stent placement, and 62 lesions were treated only with balloon angioplasty. In the case of stent use, a larger distal plaque burden was associated with restenosis, while a lower calcification angle was associated with higher patency in the case of balloon angioplasty alone. Conclusions The factors related to patency differed depending on the treating modality. The findings suggest that IVUS is a useful tool for predicting patency because it can provide a more accurate evaluation after EVT for femoropopliteal lesions.

Objective Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. Method We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. Results The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. Conclusions This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

Aims Infrequent appearance and failed induction of premature ventricular contractions (PVCs) at catheter ablation make their localization difficult and are associated with a poor procedural outcome. This study aimed to assess the effect of preprocedural oral caffeine intake on induction of PVCs during catheter ablation. Methods and results Seventy patients (age: 54 ± 14 years, 37 men) undergoing catheter ablation for monofocal PVCs were randomized to receive oral caffeine (5 mg/kg) or placebo. Before ablation, PVC counts for 5 min were performed at baseline and during isoproterenol infusion and the isoproterenol washout period. PVC count fluctuation was defined as the difference between the highest and lowest 5-min count among the three-time periods. The 5-min PVC counts during baseline and isoproterenol infusion were equivalent between the groups. However, those during the isoproterenol washout period and PVC count fluctuation were significantly higher in the caffeine group than the control group (73.1 ± 73.2 vs. 38.9 ± 28.9 beats/5 min, P = 0.012 and 69.3 ± 61.3 vs. 37.7 ± 30.9 beats/5 min, P = 0.008, respectively). The procedure and ablation times were significantly shorter in the caffeine group than the control group (105.0 ± 23.4 vs. 136.9 ± 43.2 min, P < 0.01 and 219.1 ± 104.7 vs. 283.5 ± 136.0 sec, P < 0.01, respectively). Conclusion Oral caffeine intake amplified the effect of isoproterenol infusion on PVC induction during catheter ablation. The combined use of oral caffeine intake and isoproterenol infusion can be an option to increase intraprocedural PVCs.

Atypical aortic coarctation is a rare condition associated with Takayasu arteritis, and is characterized by symptoms caused either by hypotension in the lower half of the body or secondary hypertension in the upper half of the body, and heart failure. We report a rare case of axillofemoral bypass to improve congestive heart failure for atypical aortic coarctation complicating Takayasu arteritis. Augmented vascular bed and retrograde renal blood flow after axillofemoral bypass surgery could achieve effective blood pressure control and improve renal function and cardiac function (LVEF: 30% → 55%, BNP: 2943 pg/mL → 128 pg/mL). There were two contributing factors for improvement of heart failure such as the increased vascular bed and the increase in retrograde renal blood flow. We believe that axillofemoral bypass is effective for Takayasu arteritis patients with refractory heart failure. In daily practice, careful attention should be paid to an impact of cardiorenal‐aorta interaction in atypical aortic coarctation complicating Takayasu arteritis.

Aims We aimed to determine whether shortening the duration of P2Y12 inhibitor therapy can reduce the risk of bleeding without increasing the risk of major adverse cardiovascular events following coronary stenting in patients with atrial fibrillation (AF). Methods and results The SAFE-A is a randomised controlled trial that compared one-month and six-month P2Y12 inhibitor therapy, in combination with aspirin and apixaban for patients with AF who require coronary stenting. The primary endpoint was the incidence of any bleeding events, defined as Thrombolysis In Myocardial Infarction major/minor bleeding, bleeding with various Bleeding Academic Research Consortium grades, or bleeding requiring blood transfusion within 12 months after stenting. The study aimed to enrol 600 patients but enrolment was slow. Enrolment was terminated prematurely after enrolling 210 patients (72.7±8.2 years; 81% male). The incidence of the primary endpoint did not differ between the one-month and six-month groups (11.8% vs 16.0%; hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.33-1.47; p=0.35). Conclusions The study evaluated the safety of withdrawing the P2Y12 inhibitor from triple antithrombotic prescription one month after coronary stenting. However, enrolment was prematurely terminated because it was slow. Therefore, statistical power was not sufficient to assess the differences in the primary endpoint.

INTRODUCTION Catheter ablation (CA) for long-standing persistent atrial fibrillation (LS-AF) remains challenging. We aimed to explore whether sinus rhythm (SR) restoration and left atrium (LA) function after pretreatment with antiarrhythmic drugs (AAD's) and electrical cardioversion (ECV) predict procedural outcomes. METHODS AND RESULTS We included 100 consecutive patients with LS-AF who were treated with AAD/ECV for at least 3 months before CA. The echocardiographic LA strain during reservoir phase (LASr) was assessed after pretreatment as a marker of LA fibrosis. The recurrence was recorded for ≥1 year after the last procedure. During a 34 ± 16-month follow-up period, the single and multiple procedures and pharmaceutically assisted success rates were 40% and 71%, respectively. Patients with preprocedural SR restoration and higher LASr showed a significantly higher recurrence-free probability after the last CA (logrank P = .001 and P

Background An audiovisual telesupport system that enables real-time audiovisual communications between 2 long-distance hospitals is one method of telemedicine. The usefulness and safety of radiofrequency catheter ablation (RFCA) using an audiovisual telesupport system has not been well established. Objective The purpose of this study was to evaluate the effectiveness and safety of RFCA using an audiovisual telesupport system. Methods An audiovisual telesupport system using a strictly secured virtual network was established between Kamisu Saiseikai Hospital (operator with 10 years' experience and 800 procedures) and the University of Tsukuba (advisor with >20 years' experience and 8000 procedures). We evaluated 19 initial consecutive patients who underwent RFCA using this system for tachyarrhythmia: 10 with atrial fibrillation (AF), 5 with paroxysmal supraventricular tachycardia (PSVT), 3 with premature ventricular contraction (PVC), and 1 with atrial flutter. Electrophysiological and procedural characteristics were retrospectively assessed. Results Acute success was achieved in all 19 patients without any major complications, with the advisor's audiovisual assistance. Mean procedure time and fluoroscopic time were 161 ± 44 minutes and 24 ± 14 minutes for AF, 110 ± 17 minutes and 28 ± 8 minutes for PVC, and 132 ± 19 minutes and 32 ± 2 minutes for PSVT, respectively. There was no recurrence of clinical arrhythmia in 17 of the 19 patients (89%) during 13 ± 9 month follow-up. Conclusion An audiovisual telesupport system for RFCA is a useful and safe method that enabled the electrophysiologist with limited human resources to make an optimal decision regarding procedural strategy and endpoint with the remote advisor's audiovisual assistance.

BACKGROUND Paucity of a premature ventricular complex (PVC) during ablation procedures may occur and be associated with a lower success rate. Isoproterenol (ISP) injections are commonly used to induce PVC; however, the induced tachycardia sometimes prevents the appearance of PVC. Epinephrine (EPI) administration may be an alternative strategy to induce PVC due to its smaller effect on heart rate (HR). This study sought to examine the electrophysiological impact of EPI injection, with a stepwise induction protocol, for infrequent intraprocedural PVC. METHODS We studied 78 consecutive patients who underwent catheter ablation of idiopathic frequent PVC. If no PVC was observed at the beginning of the procedure, ISP (10 µg) was injected. If clinical PVC was not induced by ISP administration, EPI (10 µg) was injected. RESULTS Of 18 patients without PVC at baseline, ISP injection induced PVC in five patients. Of the remaining 13 patients, EPI injection successfully induced PVC in seven patients (53%). The maximum HR and increments of HR after EPI injection were significantly lower than those after ISP injection (99 ± 15 vs 137 ± 15 bpm, P = .001; 22 ± 10 vs 53 ± 12 bpm, P

Higher drug concentrations in complex clinical scenarios in which multiple factors such as drug–drug interactions (DDIs) and comorbidities are simultaneously present are not necessarily rationalized in prospective clinical studies. Physiologically based pharmacokinetic (PBPK) modeling and simulation of the anti-arrhythmic drug flecainide, as an example, were utilized to quantitatively rationalize the higher flecainide concentration in a complex clinical case involving end-stage renal disease (ESRD), cirrhosis, and the co-administration of mexiletine, a CYP1A2 inhibitor. The developed flecainide PBPK model was used to evaluate the DDI effect (as measured by AUC ratio before and after inhibition) of mexiletine and the combined disease effects of ESRD and cirrhosis on flecainide exposure. The predicted DDI effect of mexiletine was negligible or weak in anuric hemodialysis with cirrhosis population (mean [5th/95th percentiles], 1.23 [0.97–1.67]), although it was negligible in healthy volunteers (1.03 [1.02–1.05]). The predicted flecainide concentrations after multiple flecainide doses (50 mg BID) in the anuric hemodialysis with cirrhosis population were comparable with the observed value (3602 ng/mL), which fell between the predicted concentrations in the absence and presence of mexiletine (3043 [718–8499] and 5914 [880–20,624] ng/mL, respectively). The PBPK simulation proposed a likely explanation that the observed higher flecainide concentration could be attributed to the combined effects of ESRD, cirrhosis, and a potential DDI with mexiletine. This approach provides quantitative insight into theoretically conceivable extremes in drug exposure occurring in complex clinical situations even if uncommon.

An increase in epicardial adipose tissue (EAT) volume is associated with the development of atrial fibrillation (AF) and coronary artery disease (CAD), but little is known about differences in its distribution. We included 50 patients with paroxysmal AF (PAF), 50 patients with CAD, and 50 control patients. Using multidetector computed tomography, EAT volumes surrounding the whole heart (total EAT), the atrium (atrial-EAT), and the ventricle (ventricular-EAT) were measured. EAT atrial/ventricular (A/V) ratio was calculated by dividing atrial- by ventricular-EAT volume. The total EAT volume indexes in the PAF and CAD groups were significantly larger than those in the control group. The atrial-EAT volume index in the PAF group was significantly larger than that in the CAD and control groups, whereas the ventricular-EAT volume index in the CAD group was significantly larger than that in the PAF and control groups. Thus, EAT A/V ratio was smaller in the CAD and control group than that in the PAF group (0.28 ± 0.12 vs. 0.38 ± 0.13 vs. 0.54 ± 0.33, P

The pulse wave transit time (PWTT) is easily measured as the time from the R wave of an electrocardiogram to the arrival of the pulse wave measured by an oxygen saturation monitor at the earlobe. We investigated whether the change of PWTT during exercise testing reflects cardiopulmonary function. Eighty-nine cardiac patients who underwent cardiopulmonary exercise testing (CPX) were enrolled. We analyzed the change of PWTT during exercise and the relationship between the shortening of the PWTT and CPX parameters. PWTT was significantly shortened from rest to peak exercise (204.6 ± 33.6 vs. 145.6 ± 26.4 msec, p < 0.001) in all of the subjects. The patients with heart failure had significantly higher PWTT at peak exercise than the patients without heart failure (152.7 ± 27.1 vs. 140.4 ± 24.8 msec, p = 0.031). The shortening of PWTT from rest to peak exercise showed significant positive correlations with the peak O2 uptake (VO2) (r = 0.56, p < 0.001), anaerobic threshold (r = 0.40, p = 0.016), and % increase of systolic blood pressure during exercise (r = 0.75, p < 0.001), and a negative correlation with the slope of the increase in ventilation versus the increase in CO2 output (VE-VCO2 slope) (r = - 0.42, p = 0.010) in the patients with heart failure. PWTT was shortened during exercise as the exercise intensity increased. In the patients with heart failure, the shortening of PWTT from rest to peak exercise was smaller in those with lower exercise capacity and those with higher VE-VCO2 slope, an established index known to reflect the severity of heart failure.

Supplemental Digital Content is available in the text., Background: Recent advancements in a 3-dimensional mapping system allow for the assessment of detailed conduction properties during sinus rhythm and thus the establishment of a strategy targeting functionally abnormal regions in scar-related ventricular tachycardia (VT). We hypothesized that a rotational activation pattern (RAP) observed in maps during baseline rhythm was associated with the critical location of VT. Methods: We retrospectively examined the pattern of wavefront propagation during sinus rhythm in patients with scar-related VT. The prevalence and features of the RAP on critical VT circuits were analyzed. RAP was defined as >90° of inward curvature directly above or at the edge of the slow conductive areas. Results: Forty-five VTs in 37 patients (66±15 years old, 89% male, 27% ischemic heart disease) were evaluated. High-density substrate mapping during sinus rhythm (median, 2524 points) was performed using the CARTO3 system before VT induction. Critical sites for reentry were identified by direct termination by radiofrequency catheter ablation in 21 VTs or by pace mapping in 12 VTs. Among them, RAP was present in 70% of the 33 VTs. Four VTs had no RAP at the critical sites during sinus rhythm, but it became visible in the mappings with different wavefront directions. Six VTs, in which intramural or epicardial isthmus was suspected, were rendered noninducible by radiofrequency catheter ablation to the endocardial surface without RAP. RAP had a sensitivity and specificity of 70% and 89%, respectively, for predicting the elements in the critical zone for VT. Conclusions: The critical zone of VT appears to correspond to an area characterized by the RAP with slow conduction during sinus rhythm, which facilitates targeting areas specific for reentry. However, this may not be applicable to intramural VT substrates and might be affected by the direction of wavefront propagation to the scar during mapping. Graphic Abstract: A graphic abstract is available for this article.

Upregulated p38 signaling is implicated in the accelerated proliferation of pulmonary artery smooth muscle cells (PA-SMCs) and the pathogenesis of pulmonary artery remodeling observed in pulmonary arterial hypertension (PAH). Previously, we reported that after endothelin-1 (ET-1) pretreatment, bone morphogenetic protein 2 (BMP2) activates p38 signaling and accelerates PA-SMC proliferation. The activity of p38 signaling is tightly regulated by the inactivation of dual-specificity phosphatase 1 (DUSP1). Activated p38 induces DUSP1 expression, forming a negative feedback loop. Prostacyclin IP receptor agonists (prostacyclin and selexipag) are used to treat PAH. In this study, we aimed to verify whether IP receptor agonists affect DUSP1 expression and accelerate the proliferation of PA-SMCs. PA-SMCs were treated with BMP2, ET-1, prostacyclin, and MRE-269, an active metabolite of selexipag, either alone or in combination. We quantified mRNA expressions using real-time quantitative polymerase chain reaction. Pulmonary artery specimens and PA-SMCs were obtained during lung transplantation in patients with PAH. Both prostacyclin and MRE-269 increased DUSP1 expression. Combined treatment with BMP2 and ET-1 induced cyclin D1 and DUSP1 expression and increased PA-SMC proliferation. MRE-269 attenuated BMP2/ET-1-induced cell proliferation. ET-1 increased DUSP1 expression in PA-SMCs from control patients but not in PA-SMCs from patients with PAH. This study showed that the p38/DUSP1 negative feedback loop is impaired in PAH, contributing to unregulated p38 activation and PA-SMC hyperplasia. IP receptor agonist MRE-269 increases DUSP1 expression and inhibit p38-mediated PA-SMC proliferation. Future elucidation of the detailed mechanism underlying reduced DUSP1 expression would be informative for PAH treatment.

BACKGROUND Aiming to establish an effective tool in new cardiac rehabilitation programs, we investigated the use of a lumbar-type hybrid assistive limb (HAL) in patients with heart failure (HF) who had difficulty in walking at the usual speed of healthy subjects (≈80 m/min).Methods and Results:We randomly assigned 28 HF patients (age, 73.1±13.8 years) to perform a sit-to-stand exercise with or without HAL. The sit-to-stand exercise was repeated as many times as possible as cardiac rehabilitation therapy over a period of 6-10 days. We measured 5 parameters before and after the completion of cardiac rehabilitation: B-type natriuretic peptide, Short Physical Performance Battery (SPPB), 6-min walking distance (6MWD), 30-s chair-stand test (CS-30), and isometric knee extensor muscle strength. The SPPB and 6MWD were significantly improved, and the CS-30 score was somewhat improved, after the exercise therapy in both the HAL and non-HAL groups. The knee extensor muscle strength improved significantly in the HAL group (0.29±0.11 to 0.35±0.11 kgf/kg, P

Isolated right ventricular (RV) infarction is extremely rare and its diagnosis may be challenging, because RV infarction most often occurs simultaneously with infarction of the inferior wall of the left ventricle. A 66-year-old man with a history of diabetes mellitus presented with cold sweat and general malaise. Although his symptoms were atypical for myocardial infarction, he was quickly diagnosed with RV infarction and successfully underwent urgent percutaneous coronary intervention. He was definitely diagnosed with isolated RV infarction by a scintigram and cardiac magnetic resonance imaging. Our review showed the importance of the combined assessment in the diagnosis of isolated RV infarction.

Background Nilotinib, a second-generation BCR-ABL tyrosine kinase inhibitor (TKI), is highly effective in the treatment of patients with chronic myeloid leukemia (CML), despite being more vasculotoxic than older TKIs such as imatinib. Herein, we present a case of nilotinib-associated vasospastic angina confirmed by an acetylcholine spasm provocation test. Case presentation A 62-year-old CML patient treated with 300 mg nilotinib twice daily complained of several episodes of rest angina and was hospitalized at our institution. Coronary angiography revealed no severe organic stenosis, and the acetylcholine spasm provocation test confirmed the diagnosis of vasospastic angina. Although treatment with a calcium channel blocker and nicorandil reduced the frequency of chest pain, angina symptoms continued to occur. At 10 months post discharge, the patient complained of increased frequency of angina; therefore, the nilotinib dosage was reduced to 150 mg twice daily. Consequently, the patient reported a significant improvement in chest symptoms. Conclusions This case report highlights the potential vasculotoxic effects of nilotinib. Cardiologists and hematologists should be vigilant for coronary artery spasm as a possible vascular adverse event caused by nilotinib.

Dilated cardiomyopathy (DCM) remains among the most refractory heart diseases because of its complicated pathogenesis, and the key molecules that cause it remain unclear.To elucidate the molecules and upstream pathways critical for DCM pathogenesis, we performed meta-analysis and co-expression analysis of RNA-sequencing (RNA-seq) datasets from publicly available databases. We analyzed three RNA-seq datasets containing comparisons of RNA expression in left ventricles between healthy controls and DCM patients. We extracted differentially expressed genes (DEGs) and clarified upstream regulators of cardiovascular disease-related DEGs by Ingenuity Pathway Analysis (IPA). Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) analysis were also used to identify the hub gene candidates strongly associated with DCM.In total, 406 samples (184 healthy, 222 DCM) were used in this study. Overall, 391 DEGs [absolute fold change (FC) ≥ 1.5; P 0.01], including 221 upregulated and 170 downregulated ones in DCM, were extracted. Seven common hub genes (LUM, COL1A2, CXCL10, FMOD, COL3A1, ADAMTS4, MRC1) were finally screened. IPA showed several upstream transcriptional regulators, including activating (NFKBIA, TP73, CALR, NFKB1, KLF4) and inhibiting (CEBPA, PPARGC1A) ones. We further validated increased expression of several common hub genes in the transverse aortic constriction-induced heart failure model.In conclusion, meta-analysis and WGCNA using RNA-seq databases of DCM patients identified seven hub genes and seven upstream transcriptional regulators.

A knock-in can generate fluorescent or Cre-reporter under the control of an endogenous promoter. It also generates knock-out or tagged-protein with fluorescent protein and short tags for tracking and purification. Recent advances in genome editing with clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein 9 (Cas9) significantly increased the efficiencies of making knock-in cells. Here we describe the detailed protocols of generating knock-in mouse and human pluripotent stem cells (PSCs) by electroporation and lipofection, respectively.

Parameters of cardiac function related to the development of pulmonary edema (PE) in acute heart failure (AHF), including right ventricular (RV) function and a mismatch of interventricular function, are not fully elucidated. The aim of this study was to verify the hypothesis that a relatively preserved RV function compared with left ventricular function may be associated with the development of PE by using two-dimensional speckle tracking echocardiography (2DSTE).Hospitalized patients with AHF at 11 institutions were enrolled. PE was defined as lung congestion on chest X-ray with hypoxemia. Patients with systolic blood pressure ≥140 mmHg on admission were defined to have hypertensive AHF. Echocardiographic analyses, including 2DSTE, were performed prior to discharge. The index of mismatch between RV and left ventricular systolic function was assessed by interventricular longitudinal strain difference (IVLSD) which was defined as RV free wall longitudinal strain and left ventricular global longitudinal strain.Of 610 patients with AHF, 422 (69.2%) had PE. In patients with PE, IVLSD (p = 0.007) and RV fractional area change ratio (p0.001) was significantly higher than those in patients without PE. In patients with non-hypertensive AHF, RV fractional area change ratio, age, ischemic etiology, and serum brain natriuretic peptide (BNP) levels were independent predictors of PE. In patients with hypertensive AHF, IVLSD, age, and serum BNP levels were independent predictors of PE.Preserved RV function might be one of the underlying mechanisms of the development of PE in AHF. Furthermore, interventricular functional mismatch might be related to the development of PE in hypertensive AHF.

BACKGROUND Although elevated levels of oxidized low-density lipoprotein (LDL) could play a critical role in vulnerable plaque, there are no studies that have compared coronary high-intensity plaque (HIP) and circulating malondialdehyde-modified (MDA)-LDL levels for the prediction of cardiac events.Methods and Results:A total of 139 patients with coronary artery stenosis (>70%) were examined with non-contrast T1-weighted magnetic resonance imaging (MRI) (HIP: n=64, non-HIP: n=75). Scheduled percutaneous coronary intervention (PCI) for culprit lesions was performed within 48 h after MRI. HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) ≥1.4. We evaluated the subsequent major adverse cardiac events (MACE) during the follow-up period (5.6±1.3 years). MDA-LDL levels were independently associated with the presence of HIP (P

Aims A high-density pace-mapping can depict an abrupt transition in paced QRS morphology from a poor to excellent match, unmasking the critical component of ventricular tachycardia (VT) isthmus from the entrance to exit. We sought to assess pace-mapping at multiple sites within the endo- and epicardial scars to identify the VT isthmus in patients with ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM). Methods and results Colour-coded maps correlating to the percentage matches between 12-lead electrocardiograms during VT and pace-mapping [referred to as correlation score maps (CSMs)] were analysed. We studied 115 CSMs (80 endo- and 35 epicardial CSMs) in 37 patients (17 ICM, 20 NICM). The CSM with an abrupt change (AC) in pacemap score (AC-type) on the endocardium was more frequently observed in ICM than in NICM [11/39 (28%) vs. 1/41 (2%); P = 0.001]. Among 35 CSMs that were analysed by the combined endo- and epicardial mapping, 10 (29%) CSMs exhibited non-AC-type on the endocardium; however, AC-type was present on the opposite epicardium. Although 24 (69%) CSMs did not show AC-type on both the endocardium and epicardium, 16 of them had either an excellent (>90%) or poor ( Conclusion The CSM may provide electrophysiological information to localize the endo- and epicardial VT isthmus. The absence of AC-type CSM on the endocardium, which is frequently observed in NICM, appears to indicate the sub-epicardial or intramural course of the critical isthmus.

Using 3-dimensional speckle-tracking echocardiography-derived activation imaging system, we visualized interventricular dyssynchrony in a repaired tetralogy of Fallot case with pacing-induced left ventricular dysfunction. The activation imaging system visualized interventricular dyssynchrony and resynchronization after cardiac resynchronization therapy and may be useful to assess electromechanical disturbance in complicated congenital heart diseases. (Level of Difficulty: Intermediate.), Graphical abstract, Using 3-dimensional speckle-tracking echocardiography-derived activation imaging system, we visualized interventricular dyssynchrony in a repaired…

To determine the influence of right bundle branch block (RBBB) on right ventricular (RV) size and function, we investigated the association between complete RBBB (CRBBB) and RV volume, function, and dyssynchrony by three-dimensional echocardiography. In this retrospective, cross-sectional study, 103 consecutive patients with adequate three-dimensional echocardiographic images were divided into the CRBBB, middle-range QRS, and narrow QRS group. RV volumetric and functional data were compared between the three groups. Among the 103 patients (44.8 ± 18.7 years, 50 men), the CRBBB group comprised 26 (25%) patients and the middle-range QRS group comprised 48 (47%). The CRBBB group showed a significant contraction delay in the RV inlet free wall and outflow tract; larger RV end-diastolic and systolic volume index (RV-EDVI, RV-ESVI); and lower RV systolic function. On dividing the CRBBB patients into two (with or without mechanical dyssynchrony), those with RV dyssynchrony showed larger RV-EDVI (121 ± 45 vs. 85 ± 25 mL/m2, P = 0.019) and RV-ESVI (93 ± 42 vs. 56 ± 20 mL/m2, P = 0.009) and smaller RV ejection fraction (24 ± 11 and 34 ± 11%, P = 0.026) than those without RV dyssynchrony. RV dyssynchrony in CRBBB patients might have an adverse effect on RV volume and function. Three-dimensional speckle-tracking echocardiography could provide additional and beneficial data during assessment of RV dyssynchrony.

Objectives This study aimed to develop a novel premature ventricular contraction (PVC) mapping method to predict PVC origins in whole ventricles by merging a magnetocardiography (MCG) image with a cardiac computed tomography (CT) image. Background MCG can noninvasively discriminate PVCs originating from the aortic sinus cusp from those originating from the right ventricular outflow tract. Methods This study was composed of 22 candidates referred for catheter ablation of idiopathic PVCs. MCG and CT were performed the same day before ablation. Estimated origins by MCG-CT imaging using the recursive null steering spatial filter algorithm were compared with origins determined by electroanatomic mapping (CARTO, Biosense Webster, Inc., Diamond Bar, California) during the ablation procedure. Radiopaque acrylic markers for the CT scan and coil markers generating a weak magnetic field during MCG measurements were used as reference markers to merge the 2 images 3-dimensionally. Results PVC origins were determined by endocardial and epicardial mapping and ablation results in 18 (86%) patients (right ventricular outflow tract in 10 patients, aortic sinus cusp in 2 patients, interventricular septum in 1 patient, near His bundle in 1 patient, right ventricular free wall in 1 patient, and left ventricular free wall in 3 patients). Estimated origins by MCG-CT imaging matched the origins determined during the procedure in 94% (17 of 18) of patients, whereas the electrocardiography algorithms were accurate in only 56% (10 of 18). Discrimination of an epicardium versus an endocardium or right- versus left-sided septum was successful in 3 of 4 patients (75%). Conclusions The diagnostic accuracy of noninvasive MCG-CT mapping was high enough to allow clinical use to predict the site of PVC origins in the whole ventricles.

Background Although atrial fibrillation (AF) is associated with exacerbation of heart failure with preserved ejection fraction (HFpEF), the relationships between maintenance of sinus rhythm (SR) and clinical outcomes in HFpEF is unknown. We investigated whether maintenance of SR was associated with better prognosis compared with rate control in patients with concomitant HFpEF and AF. Methods We conducted a retrospective, observational study of 283 patients with HFpEF and AF. Of these, 107 patients achieved maintenance of SR by catheter ablation and/or antiarrhythmic drugs (rhythm control) and 176 were treated with rate control. The propensity score (PS) for each patient in both treatment groups was estimated, resulting in selectively matched subgroups of 79 patients each. All-cause death and a composite of cardiovascular death or hospitalization for heart failure (HF) were analyzed. Results During a median follow-up period of 24 months, all-cause mortality was comparable between groups; however, maintenance of SR was significantly associated with a lower incidence of the composite endpoint [adjusted hazard ratio (HR), 0.30; 95% confidence interval, 0.18–0.98; p = 0.04] in the PS-matched cohort. The PS-adjusted multivariable analysis based on 283 pre-matched patients also revealed that rhythm control was associated with a lower rate of the composite endpoint (adjusted HR, 0.27; 95% CI, 0.12–0.61; p = 0.002). Subgroup analyses suggested that rhythm control was consistently related to the composite endpoint across a wide spectrum of HFpEF patients. Conclusions Maintenance of SR was associated with a lower risk of composite of cardiovascular death or hospitalization for HF in patients with HFpEF and AF. A randomized trial is necessary to confirm this result.

The lumbar-type Hybrid Assistive Limb (HAL) is expected to expand the possibilities of exercise therapy for severe cardiac patients who have difficulty in moving on their own legs. We investigated whether motion assistance from HAL during squat exercise could effectively reduce the cardiopulmonary burden in healthy subjects. Twelve healthy subjects (33 ± 11 years) performed squat exercise for 3 consecutive minutes at a repetition rate of 20 squats per minute with and without assistance from a lumbar-type HAL. The oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and the Borg Scale were monitored during exercise. VO2 (930 ± 207 vs 992 ± 169 mL/min, p 0.05) and the Borg Scale rating (12.8 ± 1.1 vs 13.7 ± 0.8, p 0.05) at the end of exercise were significantly lower when HAL was used. When 2 subjects who regularly perform high-intensity exercise for more than 10 h per week were excluded from the analyses, VO2, VCO2, VE, and the Borg Scale were significantly lower when HAL was used. Our results demonstrate that the lumbar-type HAL significantly reduces cardiopulmonary burden during squat exercise in healthy subjects. The effects were especially striking in sedentary subjects. Further studies on cardiac patients are expected to establish a new cardiac rehabilitation program using HAL.

Radiofrequency ablation at the aortic root has the potential risk of aortic regurgitation (AR).This study investigated the incidence and clinical features of iatrogenic AR after catheter ablation of idiopathic ventricular arrhythmias originating from the aortic root.We studied 45 consecutive patients with idiopathic ventricular arrhythmias originating from the aortic cusps (ACs; AC group; n = 32 [71%]) and papillary muscles (control group; n = 13 [29%]) who underwent ablation via a retrograde aortic approach and serial echocardiography before and within 24 hours after the ablation procedure. No patients had preexisting AR.After ablation, mild AR occurred in 5 AC group patients and 1 control group patient. Regurgitant flow was observed at the center of the aortic leaflets in 3 patients, the left coronary cusp-noncoronary cusp commissure in 2 patients, and both in 1 patient. No patients undergoing ablation only above the aortic valve developed AR. In AC group patients, the occurrence of AR was associated with a longer ablation time (24 ± 14 minutes vs 10 ± 5 minutes; P.01) and higher average output (36.6 ± 4.2 W vs 32.0 ± 3.2 W; P = .01). The same severity of AR still existed after 16.2 ± 3.6 months of follow-up. No patients required any additional medical management or surgical intervention.Iatrogenic mild AR after ablation in the aortic root occurred with a noticeable prevalence, which was associated with extensive ablation both above and below the ACs as well as catheter-related mechanical factors. Although it did not appear to aggravate the hemodynamic status during the mid-term follow-up, careful monitoring of AR progression should be considered.

Background: Ventricular fibrillation (VF) storm after myocardial infarction (MI) is a life-threatening condition that necessitates multiple defibrillations. Catheter ablation is a potentially effective treatment strategy for VF storm refractory to optimal medical treatment. However, its impact on patient survival has not been verified in a large population. Methods: We conducted a multicenter, retrospective observational study involving consecutive patients who underwent catheter ablation of post-MI refractory VF storm without preceding monomorphic ventricular tachycardia. The target of ablation was the Purkinje-related ventricular extrasystoles triggering VF. The primary outcome was in-hospital and long-term mortalities. Univariate logistic regression and Cox proportional-hazards analysis were used to evaluate clinical characteristics associated with in-hospital and long-term mortalities, respectively. Results: One hundred ten patients were enrolled (age, 65±11years; 92 men; left ventricular ejection fraction, 31±10%). VF storm occurred at the acute phase of MI (4.5±2.5 days after the onset of MI during the index hospitalization for MI) in 43 patients (39%), the subacute phase (>1 week) in 48 (44%), and the remote phase (>6 months) in 19 (17%). The focal triggers were found to originate from the scar border zone in 88 patients (80%). During in-hospital stay after ablation, VF storm subsided in 92 patients (84%). Overall, 30 (27%) in-hospital deaths occurred. The duration from the VF occurrence to the ablation procedure was associated with in-hospital mortality (odds ratio for each 1-day increase, 1.11 [95% CI, 1.03–1.20]; P =0.008). During follow-up after discharge from hospital, only 1 patient developed recurrent VF storm. However, 29 patients (36%) died, with a median survival time of 2.2 years (interquartile range, 1.2–5.5 years). Long-term mortality was associated with left ventricular ejection fraction P =0.014), New York Heart Association class ≥III (hazard ratio, 2.68 [95% CI, 1.16–6.19]; P =0.021), a history of atrial fibrillation (hazard ratio, 3.89 [95% CI, 1.42–10.67]; P =0.008), and chronic kidney disease (hazard ratio, 2.74 [95% CI, 1.15–6.49]; P =0.023). Conclusions: In patients with MI presenting with focally triggered VF storm, catheter ablation of culprit triggers is lifesaving and appears to be associated with short- and long-term freedom from recurrent VF storm. Mortality over the long-term follow-up is associated with the severity of underlying cardiovascular disease and comorbidities in this specific patient population.

Background The CRISPR/Cas9 technique has undergone many modifications to decrease the effort and shorten the time needed for efficient production of mutant mice. The use of fresh embryos consumes time and effort during oocytes preparation and fertilization before every experiment, and freeze-thawed embryos overcome this limitation. However, cryopreservation of 1-cell embryos is challenging. New method We introduce a protocol that combines a modified method for cryopreserving 1-cell C57BL/6J embryos with optimized electroporation conditions that were used to deliver CRISPR reagents into embryos, 1 h after thawing. Results Freeze-thawed 1-cell embryos showed similar survival rates and surprisingly high developmental rates compared to fresh embryos. Using our protocol, we generated several lines of mutant mice: knockout mice via non-homologous end joining (NHEJ) and knock-in mice via homology-directed repair (HDR) with high-efficient mutation rates (100%, 75% respectively) and a low mosaic rate within 4 weeks. Comparison with existing method (s) Our protocol associates the use of freeze-thawed embryos from an inbred strain and electroporation, and can be performed by laboratory personnel with basic training in embryo manipulation to generate mutant mice within short time periods. Conclusion We developed a simple, economic, and robust protocol facilitating the generation of genetically modified mice, bypassing the need of backcrossing, with a high efficiency and a low mosaic rate. It makes the preparation of mouse models of human diseases a simple task with unprecedented ease, pace, and efficiency.

Aims The objective of the study was to evaluate whether the geriatric nutritional risk index (GNRI) at discharge may be helpful in predicting the long‐term prognosis of patients hospitalized with heart failure (HF) with preserved ejection fraction (HFpEF, left ventricular ejection fraction ≥50%), a common HF phenotype in the elderly. Methods and results Overall, 110 elderly HFpEF patients (≥65 years) from the Ibaraki Cardiovascular Assessment Study‐HF (n = 838) were enrolled. The mean age was 78.5 ± 7.2 years, and male patients accounted for 53.6% (n = 59). All‐cause mortality was compared between the low GNRI (

Background Cardiac tamponade is a serious complication of catheter ablation for atrial fibrillation (AF). However, the outcomes of catheter ablation in patients of cardiac tamponade are unknown. Methods We performed catheter ablation in 2467 sessions of AF or a recurrence of AF between January 2007 and January 2016. Of these, 29 events in 27 patients (1.18%: 22 men; 64.5 ± 10.4 years; 17 with paroxysmal AF) of cardiac tamponade during or after the procedure were recorded. The clinical characteristics and outcomes of these 29 events were studied in detail. Results Of the 19 events where the ablation procedure was completed, seven events developed acute recurrence of AF (36.8%). Of the 10 events with an incomplete procedure, 10 exhibited AF recurrence (100.0%). Direct oral anticoagulants were used in seven events, and clinical outcomes were not significantly different compared to the remaining 21 events that were prescribed warfarin. Pericarditis occurred in 10 events (34.5%) after the procedure, and the incidence rate was lower in patients receiving prophylactic nonsteroidal anti‐inflammatory drugs or steroids (2/15, 13.3% vs 8/14, 57.1%; P = 0.013). Repeated sessions were performed in 12 events (two with a complete initial procedure, 10 with an incomplete initial procedure). Freedom from atrial arrhythmias was observed in 27 events (93.1%, 9 with antiarrhythmic drugs) over midterm follow‐up (3.1 ± 2.6 years). Conclusion Although cardiac tamponade caused by catheter ablation led to a high rate of acute AF recurrence and pericarditis, the midterm recurrence rates of AF are unaffected if the procedure can be completed.

Renal dysfunction results in the accumulation of various uremic toxins, including indoxyl sulphate (IS), and is a major risk factor for atrial fibrillation (AF). Experimental studies have demonstrated that IS exacerbates atrial remodelling via oxidative stress, inflammation, and fibrosis. However, its clinical impact on AF-promoting cardiac remodelling has not been described. Therefore, the purpose of this study was to clarify the relationship between basal IS levels and the 1-year outcomes after catheter ablation for the treatment of AF. Our prospective observational study included data from 125 patients with AF who underwent catheter ablation. Over a 1-year follow-up period, AF recurrence was identified in 21 patients. The 1-year AF-free survival was significantly lower in patients with high serum IS levels (≥0.65 μg/mL) than in those with low IS levels (60.1 ± 10.4% versus 85.2 ± 3.9%, P = 0.007). Univariable analysis identified that an IS concentration ≥ 0.65 μg/mL was associated with AF recurrence (hazard ratio [HR] = 3.10 [1.26–7.32], P = 0.015), and this association was maintained in multivariate analysis (HR = 3.67 [1.13–11.7], P = 0.031). Thus, in patients undergoing AF ablation, serum IS levels at baseline independently predict the recurrence of arrhythmia.

Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). However, the effects of the xanthine oxidase (XO) inhibition for AF remain to be fully elucidated. We investigated the effects of a novel XO inhibitor febuxostat on AF compared with allopurinol in hypertension rat model. Five-week-old Dahl salt-sensitive rats were fed either low-salt (LS) (0.3% NaCl) or high-salt (HS) (8% NaCl) diet. After 4 weeks of diet, HS diet rats were divided into three groups: orally administered to vehicle (HS-C), febuxostat (5 mg/kg/day) (HS-F), or allopurinol (50 mg/kg/day) (HS-A). After 4 weeks of treatment, systolic blood pressure (SBP) was significantly higher in HS-C than LS, and it was slightly but significantly decreased by treatment with each XO inhibitor. AF duration was significantly prolonged in HS-C compared with LS, and significantly suppressed in both HS-F and HS-A (LS; 5.8 ± 3.5 s, HS-C; 33.9 ± 23.7 s, HS-F; 15.0 ± 14.1 s, HS-A; 20.1 ± 11.9 s: P

Adult hearts have limited regenerative capacity. Hence, after acute myocardial infarction (MI), dead myocardial tissues are digested by immune cells and replaced by fibrosis, leading to ventricular remodeling and heart failure at the chronic stage. Direct reprogramming of the cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) with cardiac transcription factors, including Gata4, Mef2c, and Tbx5 (GMT), may have significant potential for cardiac repair. Sendai virus (SeV) vectors expressing GMT have been reported to reprogram the mouse cardiac fibroblasts into iCMs without any risk of insertional mutagenesis. In vivo reprogramming improved the cardiac function after acute MI in immunodeficient mice. However, it is unknown whether the newly generated iCMs could exist in infarct hearts for a prolonged period and SeV-GMT can improve cardiac function after MI at the chronic stage in immunocompetent mice. Here, we show that SeV vectors efficiently infect CFs in vivo and reprogram them into iCMs, which existed for at least four weeks after MI, in fibroblast-linage tracing mice. Moreover, SeV-GMT improved cardiac function and reduced fibrosis and collagen I expression at 12 weeks after MI in immunocompetent mice. Thus, direct cardiac reprogramming with SeV vectors could be a promising therapy for MI.

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86–93%, and 84–94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and &lt, 55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.

Background Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking. Methods and Results A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102–3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066). Conclusions This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.