Loss of myocardium permanently impairs cardiac function because the adult mammalian heart has limited regenerative capacity. Strategies to regenerate injured heart tissue include the transplantation of multiple types of stem cells. Among them, pluripotent stem cells (PSCs) are a promising option because of their unlimited self-renewal and unequivocal cardiomyogenic ability. To date, advances in stem cell biology allow generation of relatively homogeneous human PSC-derived cardiomyocytes (CMs). In this regard, preclinical studies of PSC-CM transplantation in rodents and larger animal models have provided convincing proof-of-concept results, triggering clinical studies in multiple countries. However, a few important uncertainties are yet to be addressed, warranting further investigation before clinical implementation of this novel therapy. An overview of the potential of stem cell therapy to provide new CMs for cardiac regeneration is presented.

Background:Heart rate (HR) is an important factor in atrial fibrillation (AF); however, it remains unclear whether the impact of HR differs between paroxysmal AF and sustained (persistent and permanent) AF.

Methods and Results:The association of resting HR during AF with adverse events (composite of all-cause death, hospitalization for heart failure, stroke/systemic embolisms, myocardial infarction, and arrhythmic events) in 1,064 paroxysmal and 1,610 sustained AF patients from the Fushimi AF Registry were investigated. These patients were divided into 4 groups based on their resting HR; ≥110 beats/min (bpm), 80–109 bpm, 60–79 bpm, and <60 bpm. The number of patients in each group was 486, 400, 172, and 22 for paroxysmal AF, and 205, 734, 645, and 71 for sustained AF, respectively. Among patients with sustained AF, a HR ≥110 bpm was associated with a higher incidence of adverse events at 1 year and during the entire follow up (median of 1,833 days) (hazard ratio [95% confidence interval] compared with a HR of 60–79 bpm: 1.90 [1.31–2.72] at 1 year, 1.38 [1.10–1.72] during the entire follow up). Patients with a HR <60 bpm showed higher incidence of adverse events at 1 year; however, the incidence of adverse events did not differ among all HR groups of paroxysmal AF.

Conclusions:Baseline HR was associated with adverse events in sustained AF, but not in paroxysmal AF.

Background:Atrial fibrillation (AF) is the most common cardiac arrhythmia; however, the current treatment strategies for AF have limited efficacy. Thus, a better understanding of the mechanisms underlying AF is important for future therapeutic strategy. A previous study (Exome-Wide Association Study (ExWAS)) identified a rare variant, rs202011870 (MAF=0.00036, GenomAD), which is highly associated with AF (OR=3.617, P<0.0001). rs202011870 results in the replacement of Leu at 396 with Arg (L396R) in a molecule, Tks5; however, the mechanism of how rs202011870 links to AF is completely unknown.

Methods and Results:The association of rs202011870 with AF was examined in 3,378 participants (641 control and 2,737 AF cases) from 4 independent cohorts by using an Invader assay. Consequences of rs202011870 in migration ability, podosome formation, and expression of inflammation-related molecules in macrophages were examined using RAW264.7 cells with a trans-well assay, immunocytochemistry, and qPCR assay. Validation of the association of rs202011870 with AF was successful. In vitro studies showed that RAW264.7 cells with L396R-Tks5 increased trans-well migration ability, and enhanced podosome formation. RAW264.7 cells with L396R-Tks5 also increased the expression of several inflammatory cytokines and inflammation-related molecules.

Conclusions:L396R mutation in Tks5 associated with AF enhances migration of macrophages and their inflammatory features, resulting in enhanced susceptibility to AF.

Background:The new guideline (NG) published by the Japanese Circulation Society (JCS) places emphasis on previous arrhythmic syncope and inducibility of ventricular fibrillation (VF) by ≤2 extrastimuli during programmed electrical stimulation (PES) for deciding the indication of an implantable cardioverter-defibrillator in patients with Brugada syndrome (BrS). This study evaluated the usefulness of the NG and compared it with the former guideline (FG) for risk stratification of patients with BrS.

Methods and Results:This was a multicenter (7 Japanese hospitals) retrospective study involving 234 patients with BrS who underwent PES at baseline (226 males; mean age at diagnosis: 44.9±13.4 years). At diagnosis, 46 patients (20%) had previous VF, 100 patients (43%) had previous syncope, and 88 patients (37%) were asymptomatic. We evaluated the difference in the incidence of VF in each indication according to the new and FGs. During the follow-up period (mean: 6.9±5.2 years), the incidence of VF was higher in patients with Class IIa indication according to the NG (NG: 16/45 patients [35.6%] vs. FG: 16/104 patients [15.4%]), while the incidence of VF in patients with other than class I or IIa indication was similarly low in both guidelines (NG: 2/143 patients [1.4%] vs. FG: 2/84 patients [2.4%]).

Conclusions:This study validated the usefulness of the NG for risk stratification of BrS patients.

Background:Approximately one-third of patients with advanced heart failure (HF) do not respond to cardiac resynchronization therapy (CRT). We investigated whether the left ventricular (LV) conduction pattern on magnetocardiography (MCG) can predict CRT responders.

Methods and Results:This retrospective study enrolled 56 patients with advanced HF (mean [±SD] LV ejection fraction [LVEF] 23±8%; QRS duration 145±19 ms) and MCG recorded before CRT. MCG-QRS current arrow maps were classified as multidirectional (MDC; n=28) or unidirectional (UDC; n=28) conduction based on a change of either ≥35° or <35°, respectively, in the direction of the maximal current arrow after the QRS peak. Baseline New York Heart Association functional class and LVEF were comparable between the 2 groups, but QRS duration was longer and the presence of complete left bundle branch block and LV dyssynchrony was higher in the UDC than MDC group. Six months after CRT, 30 patients were defined as responders, with significantly more in the UDC than MDC group (89% vs. 14%, respectively; P<0.001). Over a 5-year follow-up, Kaplan-Meyer analysis showed that adverse cardiac events (death or implantation of an LV assist device) were less frequently observed in the UDC than MDC group (6/28 vs. 15/28, respectively; P=0.027). Multivariate analysis revealed that UDC on MCG was the most significant predictor of CRT response (odds ratio 69.8; 95% confidence interval 13.14–669.32; P<0.001).

Conclusions:Preoperative non-invasive MCG may predict the CRT response and long-term outcome after CRT.

Background:Extended dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is frequently used for high-risk patients in real-world practice. However, there are limited data about the long-term efficacy of extended DAPT after percutaneous coronary intervention (PCI).

Methods and Results:This study investigated 1,470 patients who underwent PCI. The study population was divided into 2 groups based on DAPT duration: guideline-based DAPT (G-DAPT; DAPT ≤12 months after PCI; n=747) and extended DAPT (E-DAPT; DAPT >12 months after PCI; n=723). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as cardiac death, myocardial infarction (MI), repeat target vessel revascularization, or stroke. The median follow-up duration was 80.8 months (interquartile range 60.6–97.1 months). The incidence of MACCE was similar in the G-DAPT and E-DAPT groups (21.0% vs. 18.3%, respectively; P=0.111). However, the E-DAPT group had a lower incidence of non-fatal MI (hazard ratio [HR] 0.535; 95% confidence interval [CI] 0.329–0.869; P=0.011), and target lesion revascularization (HR 0.490; 95% CI 0.304–0.792; P=0.004), and stent thrombosis (HR 0.291; 95% CI 0.123–0.688; P=0.005). The incidence of bleeding complications, including major bleeding, was similar between the 2 groups (5.2% vs. 6.3%, respectively; P=0.471).

Conclusions:Although E-DAPT after DES implantation was not associated with a reduced rate of MACCE, it was associated with a significantly lower incidence of non-fatal MI, TLR, and stent thrombosis.

Background:With the rapid spread of COVID-19, hospitals providing percutaneous coronary intervention (PCI) were placed in unique and unfamiliar circumstances. This study evaluated variations in the treatment of coronary artery disease according to time course of the COVID-19 pandemic in Japan.

Methods and Results:The Japanese Association of Cardiovascular Intervention and Therapeutics performed serial surveys during the pandemic (in mid-April, late-April and mid-May 2020) with queries regarding the implementation of PCI. Hospitals were asked about their treatment strategies for elective PCI and emergency PCI for ST-elevation myocardial infarction (STEMI) and high-risk acute coronary syndrome (ACS) patients. Most hospitals opted to perform primary PCI in the usual manner at the beginning of the pandemic. As the pandemic progressed, hospitals in the 7 populated areas downgraded the performance of PCI for chronic coronary syndrome and high-risk ACS, but not for STEMI patients. After the state of emergency was lifted in most prefectures in mid-May, the rate of PCI gradually normalized. Screening tests, such as polymerase chain reaction and chest computed tomography, in ACS were frequently used.

Conclusions:The COVID-19 pandemic greatly affected PCI treatment in Japan. However, even in the most critical situations during the pandemic, most institutions continued to perform primary PCI normally for STEMI patients.

Background:Sedentary behavior may be an independent risk factor for cardiovascular events. This study aimed to clarify the effects of extended sedentary time in patients with diabetic kidney disease (DKD) on the risk of all-cause death and new events.

Methods and Results:A prospective cohort study was performed over 39 months. The study included 173 patients with DKD who completed the International Physical Activity Questionnaire (IPAQ) (101 men; mean age, 71±11 years); 37 patients (21.4%) were diagnosed with cardiovascular disease (CVD). New events were defined as all-cause death, cerebral stroke, or CVD requiring hospitalization or commencing hemodialysis (HD). Data were analyzed using a multivariate Cox proportional hazard regression model with variables, including sedentary time. There were 34 cases of new events during the observation period, including 4 cases of stroke, 20 cases of CVD, 4 cases of HD implementation, and 6 cases of death. Hazard ratio (HR) calculations for the new event onset group identified sedentary time as a significant independent variable. The independent variable that was identified as a significant predictor of new events was the sedentary time (60 min/day; HR: 1.23, 95% CI: 1.05–1.45, P=0.012).

Conclusions:Extended sedentary time increased the risk of new cardiovascular or renal events and/or all-cause death in patients with DKD.

Background:The bridge-to-bridge (BTB) strategy, a conversion to durable left ventricular assist device (LVAD) after stabilization using surgical temporary mechanical circulatory supports for a couple of months, is not uncommon in Japan. However, its effect on clinical outcomes in comparison with a primary durable LVAD implantation strategy remains unknown.

Methods and Results:Data of 837 consecutive patients (median age 45, 73% males) who underwent durable LVAD implantation as BTB (n=168) or primary implant (n=669) between April 2011 and April 2019 were retrospectively reviewed from the prospective multicenter Japanese mechanically assisted circulatory support registry. The BTB group was younger and had comparable end-organ function, better hemodynamic profile, and longer operative time compared with the primary implant group at baseline. The 3-year survival was 80% vs. 87% (P=0.007) for the BTB and primary implant groups respectively, with greater observed rates of stroke and infection as the predominant causes of death. The BTB strategy was independently associated with increased 3-year mortality (hazard ratio 2.69 [1.43–5.07], P=0.002) in addition to other significant risk factors.

Conclusions:The BTB cohort had comparable baseline characteristics to the primary implant cohort at the time of durable LVAD conversion, but had lower 3-year survival. Detailed analysis clarifying the causality of this finding should improve outcomes with the BTB strategy.

Background:This study identified predictors of hospital mortality after successful weaning of patients with cardiogenic shock off venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support.

Methods and Results:Adult patients who received peripheral VA ECMO from January 2012 to April 2017 were reviewed retrospectively. After excluding patients who died on ECMO support, predictors for survival to discharge were investigated in patients who were successfully weaned off ECMO. Of 191 patients successfully weaned off ECMO, 143 (74.9%) survived to discharge. The prevalence of a history of stroke and coronary artery disease, as well as ECMO-related complications, including newly developed stroke and sepsis, was a higher in patients who did not survive to discharge than in those who did. On the day of ECMO weaning, Sequential Organ Failure Assessment score and serum lactate were higher in patients who did not survive to discharge, although there was no significant difference in blood pressure and the use of vasoactive drugs between the 2 groups. On multivariable analysis, stroke and sepsis during ECMO support, a lower Glasgow Coma Scale and acute kidney injury requiring continuous renal replacement therapy after weaning were significant predictors for in-hospital mortality.

Conclusions:Complications that occurred during ECMO and the presence of extracardiac organ dysfunction after weaning were associated with in-hospital mortality in patients with cardiogenic shock who were successfully weaned off ECMO.

Background:Appropriate indications and protocols for induction therapy using basiliximab have not been fully established in heart transplant (HTx) recipients. This study elucidated the influence of induction therapy using basiliximab along with delayed tacrolimus (Tac) initiation on the outcomes of high-risk HTx recipients.

Methods and Results:A total of 86 HTx recipients treated with Tac-based immunosuppression were retrospectively reviewed. Induction therapy was administered to 46 recipients (53.5%) with impaired renal function, pre-transplant sensitization, and recipient- and donor-related risk factors (Induction group). Tac administration was delayed in the Induction group. Induction group subjects showed a lower cumulative incidence of acute cellular rejection grade ≥1R after propensity score adjustment, but this was not significantly different (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.37–1.08, P=0.093). Renal dysfunction in the Induction group significantly improved 6 months post-transplantation (P=0.029). The cumulative incidence of bacterial or fungal infections was significantly higher in the Induction group (HR: 10.6, 95% CI: 1.28–88.2, P=0.029).

Conclusions:These results suggest that basiliximab-based induction therapy with delayed Tac initiation may suppress mild acute cellular rejection and improve renal function in recipients with renal dysfunction, resulting in its non-inferior outcome, even in high-risk patients, when applied to the appropriate recipients. However, it should be carefully considered in recipients at a high risk of bacterial and fungal infections.

Background:The clinical significance of osteoporosis in chronic heart failure (CHF) remains unclear.

Methods and Results:A total of 303 CHF patients (75 years, [interquartile range (IQR) 66–82 years]; 41% female) were retrospectively examined. Bone mineral densities (BMDs) at the lumbar spine, femoral neck, and total femur were measured by using dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when the BMD at any of the 3 sites was <70% of the Young Adult Mean percentage (%YAM). The prevalence of osteoporosis in CHF patients was 40%. Patients with osteoporosis were older (79 [IQR, 74–86] vs. 72 [IQR, 62–80] years), included a large percentage of females, had slower gait speed and had a lower body mass index. Multivariate logistic regression analysis indicated that sex, BMI, gait speed, loop diuretics use and no use of direct oral anticoagulants (DOACs) were independently associated with osteoporosis. Kaplan-Meier survival curves showed that the rate of death and heart failure hospitalization was higher in patients with osteoporotic BMD at 2 or 3 sites than in patients without osteoporosis (hazard ratio 3.45, P<0.01). In multivariate Cox regression analyses, osteoporotic BMD at 2 or 3 sites was an independent predictor of adverse events after adjustment for prognostic markers.

Conclusions:Loop diuretics use and no DOACs use are independently associated with osteoporosis in CHF patients. Osteoporosis is a novel predictor of worse outcome in patients with CHF.

Background:The relationship between the characteristics of tissue protrusion detected by using optical coherence tomography (OCT) and the findings of coronary angioscopy (CAS) immediately after stent implantation were evaluated.

Methods and Results:A total of 186 patients (192 stents) underwent OCT before and after stenting and were observed by using CAS immediately after stenting and at the chronic phase. Patients were assigned to irregular protrusion, smooth protrusion, and disrupted fibrous tissue protrusion groups according to OCT findings. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after stent implantation. The grade of yellow color (YC) and neointimal coverage (NC), and incidence of thrombus in the stented segment were evaluated by using CAS. After stent implantation, maximum YC grade (smooth, 0.64±0.80; disrupted fibrous tissue, 0.50±0.77; irregular, 1.50±1.09; P<0.0001), a prevalence of Max-YC grade of 2 or 3 (smooth, 17%; disrupted fibrous tissue, 17%; irregular, 50%; P<0.0001) and thrombus (smooth, 15%; disrupted fibrous tissue, 10%; irregular, 69%; P=0.0005), and elevated hs-CRP levels (smooth, 0.22±0.89; disrupted fibrous tissue, −0.05±0.29; irregular, 0.75±1.41; P=0.023) were significantly higher in irregular protrusion than in the other 2 groups. In the chronic phase, maximum- and minimum-NC grade and heterogeneity index, and thrombus did not differ significantly among the 3 groups.

Conclusions:Irregular protrusion was associated with atherosclerotic yellow plaque, incidence of thrombus, and vascular inflammation. The angioscopic findings in the chronic phase may endorse the clinical efficacy of second- and third-drug eluting stents, regardless of the tissue protrusion type.

Background:Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.

Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus.

Conclusions:Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

Background:Optical flow ratio (OFR) is a recently developed method for functional assessment of coronary artery disease based on computational fluid dynamics of vascular anatomical data from intravascular optical coherence tomography (OCT). The purpose of this study was to investigate the relationship between OFR and fractional flow reserve (FFR) in stent-treated arteries immediately after percutaneous coronary intervention (PCI).

Methods and Results:The OFR and FFR were measured in 103 coronary arteries immediately after successful PCI with a stent. An increase in the OFR and FFR values within the stent was defined as in-stent ∆OFR and ∆FFR, respectively. The values of FFR and OFR were 0.89±0.06 and 0.90±0.06, respectively. OFR was highly correlated with FFR (r=0.84, P<0.001). OFR showed a good agreement with FFR, presenting small values of mean difference and root-mean-squared deviation (FFR–OFR: −0.01±0.04). In-stent ∆OFR showed a moderate correlation (r=0.69, P<0.001) and good agreement (in-stent ∆FFR – in-stent ∆OFR: 0.00±0.02) with in-stent ∆FFR.

Conclusions:OFR showed a high correlation and good agreement with FFR in stent-treated arteries immediately after PCI.

Background:The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. This study aimed to investigate the role of circular RNA-0010283 (circ_0010283) in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and the associated action mechanism.

Methods and Results:The expression of circ_0010283 was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was detected by using flow cytometry assay. A transwell assay was performed to observe migration and invasion, and a scratch assay was implemented to test migration. The expression of proliferation, apoptosis and migration/invasion-related proteins was measured by using a western blot. The targeted relationship was predicted by using a bioinformatics tool (Starbase) and verified by using a dual-luciferase reporter assay, a RNA immunoprecipitation (RIP) assay and a RNA pull-down assay. circ_0010283 was highly expressed in serum samples from atherosclerosis patients and ox-LDL-treated human VSMCs (HVSMCs). circ_0010283 knockdown suppressed ox-LDL-induced proliferation, migration and invasion in HVSMCs. MicroRNA-133a-3p (miR-133a-3p) was confirmed as a target of circ_0010283, and miR-133a-3p deficiency reversed the effects of circ_0010283 knockdown. Moreover, pregnancy-associated plasma protein A (PAPPA) was targeted by miR-133a-3p, and PAPPA overexpression reversed the effects of miR-133a-3p restoration. Interestingly, circ_0010283 could regulate PAPPA expression by mediating miR-133a-3p.

Conclusions:circ_0010283 participated in ox-LDL-induced dysfunctions of HVSMCs by modulating the miR-133a-3p/PAPPA pathway, suggesting that circ_0010283 might be associated with atherosclerosis pathogenesis.

Background:Although advances in cardiac surgery have led to an increased number of survivors with congenital heart disease (CHD), epidemiological data regarding the pregnancies and deliveries of patients with repaired CHD are scarce.

Methods and Results:In this study, we retrospectively reviewed the clinical outcomes of pregnancies and deliveries of women with repaired CHD. Overall, 131 women with repaired CHD were enrolled and there were 269 gestations. All patients were classified as New York Heart Association (NYHA) Class I or II. The prevalence of cesarean sections was higher in patients with (CyCHD) than without (AcyCHD) a past history of cyanosis (51% vs. 19%, respectively; P<0.01). There were 228 offspring from 269 gestations and the most prevalent neonatal complication was premature birth (10%), which was more frequent in the CyCHD than AcyCHD group (15.7% vs. 5.6%, respectively; P<0.01). Five maternal cardiac complications during delivery were observed only in the CyCHD group (8%); these were classified as NYHA Class II and none was fatal.

Conclusions:Delivery was successful in most women with repaired CHD who were classified as NYHA Class I or II, although some with CyCHD and NYHA Class II required more attention. Cesarean sections were more common in the CyCHD than AcyCHD group, and CyCHD may be a potential risk for preterm deliveries.

Background:Congenital heart disease (CHD) is often diagnosed prenatally using fetal echocardiography, but few studies have evaluated the accuracy of these fetal cardiac diagnoses in detail. We investigated the discrepancy between pre- and postnatal diagnoses of CHD and the impact of discrepant diagnoses.

Methods and Results:This retrospective study at a tertiary institution included data from the medical records of 207 neonates with prenatally diagnosed CHD admitted to the cardiac neonatal intensive care unit between January 2011 and December 2016. Pre- and postnatal diagnoses of CHD differed in 12% of neonates. Coarctation of the aorta and ventricular septal defects were the most frequent causes of discrepant diagnosis. Unexpected treatments were added to 38% of discrepant diagnostic cases. However, discrepant diagnoses did not adversely affect the clinical course. The 9% of the 207 neonates who required invasive intervention within 24 h of delivery were accurately diagnosed prenatally.

Conclusions:Pre- and postnatal diagnoses differed in only a few neonates, with differences not adversely affecting the clinical course. Neonates who required invasive intervention immediately after delivery were accurately diagnosed prenatally. Prenatal diagnosis thus seems to contribute to improved prognosis in neonates with CHD.

Background:The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.

Methods and Results:ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32–0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34–1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74–1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09).

Conclusions:Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.

Background:Transcatheter aortic valve implantation (TAVI) is an established treatment for symptomatic patients with severe aortic stenosis (AS). Sometimes patients with severe AS taking immunosuppressants are encountered. The effect of immunosuppressive therapy on clinical outcomes in patients with AS following TAVI were investigated.

Methods and Results:In total, 282 consecutive patients with severe AS who underwent transfemoral TAVI from January 2016 to December 2018 at St. Marianna University School of Medicine were reviewed. They were divided into 2 groups: the immunosuppressants group (IM group) in which patients continually used immunosuppressive drugs (n=22) and the non-immunosuppressants group (non-IM group) (n=260). The composite endpoints of a major adverse cardiovascular and cerebrovascular event (MACCE) defined as non-lethal myocardial infarction, unstable angina pectoris, heart failure requiring hospitalization, stroke, and cardiovascular death were evaluated. There were no differences in the incidence of vascular access complications (32% vs. 20%, P=0.143) and the rate of procedure success (100% vs. 93%, P=0.377) between the IM and non-IM groups. During the median follow-up period of 567 (16–1,312) days after the TAVI procedure, there were no significant differences between the IM and non-IM groups in the incidence of infectious complications (14% vs. 9%, P=0.442) or MACCE (18% vs. 20%, respectively; P=0.845).

Conclusions:The use of IM after TAVI is not associated with increased vascular access complications or mid-term MACCE in patients with severe AS treated with TAVI.

Background:Lead-induced tricuspid regurgitation (TR) after cardiac implantable electronic device (CIED) implantation is not fully understood. This study aimed to reveal the features of lead-induced TR by 3-dimensional echocardiography (3DE) in patients with heart failure (HF) events after CIED implantation.

Methods and Results:In 143 patients, 3DE assessments for the tricuspid valve (TV) and right ventricular morphologies were sequentially performed within 3 days after CIED implantations, during TR exacerbations, and at ≥6 months after TR exacerbations. TR exacerbations were observed in 29 patients (median 10 months after CIED implantation, range 1–28 months), 15 of whom had lead-induced TR. In the 29 patients, the tenting height of the TV, tricuspid annular (TA) height, and TA area at baseline were independent predictors for worsening TR. In patients with lead-induced TR, tenting height of the TV and TA area were identified as the risk factors. In addition, all patients with a lead positioned on a leaflet immediately after CIED implantations developed lead-induced TR. At follow up, TR exacerbation of lead-induced TR persisted with TA remodeling, but it was improved in the lead non-related-TR group.

Conclusions:TA remodeling at baseline and a lead location on a leaflet immediately after CIED implantation were associated with lead-induced TR in patients with HF events after CIED implantation. Persistent TA remodeling may make lead-induced TR refractory against HF treatments.

Background:We investigated the long-term clinical and hemodynamic outcomes after aortic valve replacement (AVR) with a 17-mm mechanical valve.

Methods and Results:Between January 2005 and December 2011, 80 patients with aortic stenosis underwent AVR with the 17-mm St. Jude Medical Regent prosthetic valve. Echocardiography was performed preoperatively, at discharge, and at follow-up, which was performed at least 2 years postoperatively (median interval, 7.3 years). Prosthesis-patient mismatch (PPM) was defined as an indexed effective orifice area <0.85 cm²/m²at discharge and occurred in 25 patients (31%). The median follow-up period was 8.7 years (100% complete). Overall in-hospital mortality was 2.5% (2 patients) with 27 late deaths (34%). The 5- and 10-year survival rates were 78.7% and 63.0%, respectively. Peripheral arterial disease and concomitant mitral valve repair were independent predictors of late mortality. The 5- and 10-year freedom from major adverse valve-related events (MAVRE) rates were 91.6% and 83.5%, respectively. PPM at discharge did not affect long-term survival, freedom from MAVRE, or freedom from heart failure. Echocardiographic data at follow-up revealed a significant reduction in the mean left ventricular mass index (LVMI). LVMI reduction observed at follow-up was similar between patients with and without PPM.

Conclusions:AVR with the 17-mm mechanical prosthesis had acceptable long-term clinical and hemodynamic outcomes. Significant reduction in LVMI was observed regardless of PPM.