Endomyocardial biopsy (EMB) has been established in parallel with the development of percutaneous catheter technology for the diagnosis of cardiac diseases. It was developed in the early 1960 s in Japan by Drs. Konno, Sakakibara and Sekiguchi of Tokyo Women’s Medical University. EMB is a valuable and useful, but invasive, modality for making a definite diagnosis in diseases such as myocarditis and secondary cardiomyopathies, which are often difficult to diagnose by imaging modality alone. In the field of heart transplantation, the histology of EMB helps monitor rejection to allografts. In cases of chronic heart failure, fibrosis and degeneration of cardiomyocytes are very important findings of heart remodeling. Recently, molecular biology technology has been applied to EMB specimens to get more detailed information. However, we must also recognize that EMB is an invasive examination that should not be performed without skillful cardiac catheterization experience to avoid complications. In this review as a message from pathologists, we present key cardiac histopathology using EMB, in a way that allows one to imagine whole cardiac pathological conditions. We also describe the current role of EMB and its significance in order to encourage young cardiologists to perform EMB to see another world of pathology.

The discussion of neurocritical care management in post-cardiac arrest syndrome (PCAS) has generally focused on target values used for targeted temperature management (TTM). There has been less attention paid to target values for systemic and cerebral parameters to minimize secondary brain damage in PCAS. And the neurologic indications for TTM to produce a favorable neurologic outcome remain to be determined. Critical care management of PCAS patients is fundamental and essential for both cardiologists and general intensivists to improve neurologic outcome, because definitive therapy of PCAS includes both special management of the cause of cardiac arrest, such as coronary intervention to ischemic heart disease, and intensive management of the results of cardiac arrest, such as ventilation strategies to avoid brain ischemia. We reviewed the literature and the latest research about the following issues and propose practical care recommendations. Issues are (1) prediction of TTM candidate on admission, (2) cerebral blood flow and metabolism and target value of them, (3) seizure management using continuous electroencephalography, (4) target value of hemodynamic stabilization and its method, (5) management and analysis of respiration, (6) sedation and its monitoring, (7) shivering control and its monitoring, and (8) glucose management. We hope to establish standards of neurocritical care to optimize brain function and produce a favorable neurologic outcome.

Background:Efficacy of catheter ablation (CA) of asymptomatic persistent atrial fibrillation (AF) remains unclear. We assessed the quality of life (QOL), exercise performance (EP), and plasma B-type natriuretic peptide (BNP) levels following CA in patients with asymptomatic AF.

Methods and Results:We enrolled 34 patients with asymptomatic persistent AF. QOL, was assessed by 2 questionnaires: the Short Form-36 (SF-36) and a QOL questionnaire specific for AF (AFQLQ). The QOL, EP, and plasma BNP level were examined before and 6 months after CA. In the SF-36 survey 5 of 8 components and all 3 subsets of the AFQLQ significantly improved in the patients without recurrences (30 patients, 88%), but there were no differences in those with recurrences. In patients without recurrences, there was an increase in the metabolic equivalents of task (10.2±2.3 vs. 11.6±2.3 METs, P<0.0001), duration of maximal exercise (476±144 vs. 605±143 s, P<0.0001), and plasma BNP decrease (146.6±124.3 vs. 33.8±35.6 pg/dL, P<0.0001), with a linear correlation in the increased duration of exercise and plasma BNP decrease (R=0.620, P<0.0001).

Conclusions:Maintenance of sinus rhythm after successful CA improved the QOL, EP, and plasma BNP level in patients with asymptomatic persistent AF. CA may be primarily applicable in such patients with previously unrecognized impairment in their QOL and EP.

Background:The mechanism and time course of in-stent restenosis (ISR) after implantation of second-generation DES have not yet been fully elucidated. We sought to evaluate the differences in tissue characteristics between the different phases of ISR after second-generation DES implantation using optical coherence tomography (OCT).

Methods and Results:From June 2010 to December 2015, 324 consecutive patients with 337 ISR lesions underwent OCT. Of these, we analyzed 53 lesions in 53 patients who had their first ISR after second-generation DES implantation and underwent OCT before any procedures. According to the timing of ISR, the patients were divided into the early group (within 1 year: E-ISR, n=30) and late group (beyond 1 year: L-ISR, n=23). Quantitative parameters and qualitative characteristics of the neointima were evaluated. In the minimum lumen area site analysis, the E-ISR group had more frequently homogeneous intima than the L-ISR group (26.7% vs. 4.4%, P=0.02). The frequencies of neointima with lipid-laden, thin-cap fibroatheroma, neovascularization and macrophage infiltration were significantly higher in the L-ISR group than in the E-ISR group (30.0% vs. 69.6%, P<0.01; 0.0% vs. 26.1%, p <0.01; 6.7% vs. 26.1%, P=0.049; 3.3% vs. 26.1%, P=0.01, respectively).

Conclusions:Neointimal tissue characteristics differed between E-ISR and L-ISR after second-generation DES implantation. E-ISR was mainly caused by neointimal hyperplasia, whereas neoatherosclerosis was the main mechanism of L-ISR.

Background:Few studies have evaluated the prevalence and clinical outcomes of ad hoc percutaneous coronary intervention (PCI), performing diagnostic coronary angiography and PCI in the same session, in stable coronary artery disease (CAD) patients.

Methods and Results:From the CREDO-Kyoto PCI/CABG registry cohort-2, 6,943 patients were analyzed as having stable CAD and undergoing first PCI. Ad hoc PCI and non-ad hoc PCI were performed in 1,722 (24.8%) and 5,221 (75.1%) patients, respectively. The cumulative 5-year incidence and adjusted risk for all-cause death were not significantly different between the 2 groups (15% vs. 15%, P=0.53; hazard ratio: 1.15, 95% confidence interval: 0.98–1.35, P=0.08). Ad hoc PCI relative to non-ad hoc PCI was associated with neutral risk for myocardial infarction, any coronary revascularization, and bleeding, but was associated with a trend towards lower risk for stroke (hazard ratio: 0.78, 95% confidence interval: 0.60–1.02, P=0.06).

Conclusions:Ad hoc PCI in stable CAD patients was associated with at least comparable 5-year clinical outcomes as with non-ad hoc PCI. Considering patients’ preference and the cost-saving, the ad hoc PCI strategy might be a safe and attractive option for patients with stable CAD, although the prevalence of ad hoc PCI was low in the current study population.

Background:Prosthesis-patient mismatch (PPM) is associated with increased mid-term and long-term mortality rates after aortic valve replacement (AVR). This study aimed to evaluate the efficacy of the Carpentier-Edwards Perimount Magna and Magna Ease (CEPMs) aortic bioprostheses to reduce the incidence of PPM.

Methods and Results:Altogether, 282 consecutive patients (113 women, mean age 69.9±9.9 years) underwent AVR with a CEPMs between 2008 and 2015. They were divided into 3 groups based on the risk of PPM as a result of their body surface area and aortic annular diameter (BSA/AnnD ratio): low-risk (LR) group: 0.64±0.05 m²/cm (n=94); medium-risk (MR) group: 0.73±0.02 m²/cm (n=94); high-risk (HR) group: 0.83±0.05 m²/cm (n=94). The 30-day mortality rate was 0.4%. The 5-year actuarial survival rates were 93.2%, 92.3%, and 94.8% for groups LR, MR, and HR, respectively. No explants as a result of structural valve deterioration occurred. No patients showed severe PPM, defined as a measured effective orifice area index (EOAI) <0.65 cm²/m². Although there were significant (P<0.05) differences in EOAI (0.98±0.2, 0.90±0.21, and 0.88±0.1 cm²/m²among the LR, MR, and HR groups, respectively), the corresponding transvalvular mean pressure gradients (13.0±5.5, 12.3±4.0, 12.7±5.3 mmHg) and regression rates of the left ventricular mass (29.8%, 28.7%, 28.9%) were similar among groups.

Conclusions:CEPMs provide low surgical risk and reduce the risks of PPM, even in HR patients, with excellent hemodynamics.

Background:Patients with liver cirrhosis (LC) have a higher risk for cardiac surgery, but population-based long-term follow-up studies are lacking. The aim of this study was therefore to validate the long-term outcome of cardiac surgery in patients with LC.

Methods and Results:Data were obtained from Taiwan’s National Health Insurance Database, 1997–2011. This study included 1,040 LC patients and 1,040 matched controls without LC. The actuarial survival rate at 1, 5 and 10 years in the LC cohort was 68%, 50% and 41%: significantly lower than that of the control cohort at 81%, 68% and 62% at 1, 5 and 10 years after cardiac surgery. Compared with the matched control cohort, the LC group had a higher risk of liver and heart failure readmission (P<0.001) during the follow-up period. In addition, the LC cohort had a higher risk of liver causes of death than did the control cohort (12.6% vs. 1.2%). In the LC cohort, 51% of deaths were due to hepatocellular carcinoma. And in the LC group, those with valve surgery and advanced cirrhosis had a lower survival rate (P=0.002, P=0.001).

Conclusions:Even after successful cardiac surgery, long-term outcome is unsatisfactory in LC patients because of the progressive deterioration of liver function.

Background:There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS).

Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3,815 consecutive patients with severe AS. Among 1,196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P<0.001, respectively). On landmark analysis at 30 days after AVR, the differences in mortality and HF hospitalization between the 2 groups were mainly observed beyond 30 days.

Conclusions:When managed with the initial AVR strategy, the long-term outcomes of symptomatic severe AS were worse than those of asymptomatic severe AS. Early AVR strategy might be recommended in some selected asymptomatic severe AS patients with reasonable operative risk.

Background:Periodic leg movements during sleep (PLM) are characterized by regularly recurring movement of the legs during sleep. Although PLM is common and a predictor of death in patients with chronic heart failure, the clinical significance of PLM in hospitalized patients with a reduced left ventricular ejection fraction (LVEF) following acute decompensated heart failure (ADHF) remains unknown.

Methods and Results:After initial improvement of acute signs and symptoms of ADHF, 94 consecutive patients with reduced LVEF who underwent polysomnography were enrolled. They were divided into 2 groups based on the presence or absence of severe PLM defined as PLM index ≥30. The risks for clinical events, composite of all-cause death and rehospitalization, were assessed using a stepwise multivariable Cox proportional model including variables showing P<0.10 in univariate analyses. Severe PLM was observed in 21 patients (22%). At a median follow-up of 5.2 months, 30 patients experienced clinical events (32%). In the multivariable analysis, the presence of severe PLM was significantly associated with increasing clinical events (hazard ratio, 2.16; 95% confidence interval, 1.03–4.54; P=0.042) independent of hemoglobin level and the severity of sleep-disordered breathing.

Conclusions:In hospitalized patients with systolic dysfunction following ADHF, severe PLM was prevalent and significantly associated with increased risk of death and/or rehospitalization.

Background:This paper examines the current status of radiation exposure to patients in myocardial perfusion imaging (MPI) in Asia.

Methods and Results:Laboratories voluntarily provided information on MPI performed over a 1-week period. Eight best practice criteria regarding MPI were predefined by an expert panel. Implementation of ≥6 best practices (quality index [QI] ≥6) was pre-specified as a desirable goal for keeping radiation exposure at a low level. Radiation effective dose (ED) in 1,469 patients and QI of 69 laboratories in Asia were compared against data from 239 laboratories in the rest of the world (RoW). Mean ED was significantly higher in Asia (11.4 vs. 9.6 mSv; P<0.0001), with significantly lower doses in South-East vs. East Asia (9.7 vs. 12.7 mSv; P<0.0001). QI in Asia was lower than in RoW. In comparison with RoW, Asian laboratories used thallium more frequently, used weight-based technetium dosing less frequently, and trended towards a lower rate of stress-only imaging.

Conclusions:MPI radiation dose in Asia is higher than that in the RoW and linked to less consistent use of laboratory best practices such as avoidance of thallium, weight-based dosing, and use of stress-only imaging. Given that MPI is performed in Asia within a diverse array of medical contexts, laboratory-specific adoption of best practices offers numerous opportunities to improve quality of care.

Background:The effect of prior use of aspirin (ASA) on the onset of acute coronary syndrome (ACS) has not been clarified. This study used optical coherence tomography (OCT) to investigate the morphological features of culprit lesions of ACS in patients with prior ASA use.

Methods and Results:In total, 442 patients with their first ACS episode undergoing OCT for the culprit lesions were investigated. Clinical characteristics, OCT findings, and adverse events at 30 days were compared between patients with prior ASA use and ASA-naïve patients (non-ASA). 67 patients (15.2%) had received ASA at presentation. The ASA group was older, had higher frequency of dyslipidemia and hypertension, and lower renal function than the non-ASA group. Non-ST-elevation ACS was more prevalent in the ASA than in the non-ASA group (79.1 vs. 53.6%, P<0.001). Propensity score matching yielded 49 patients in both groups. OCT revealed less frequent thrombi in the ASA than in the non-ASA group in both the entire (37.3 vs. 75.2%, P<0.001) and score-matched cohorts (38.8 vs. 75.5%, P<0.001), whereas no significant difference was observed in plaque characteristics. Rate of adverse events did not differ between the ASA and the non-ASA groups in the matched cohort.

Conclusions:With a first ACS presentation, patients with prior ASA use were more likely to present with non-ST-elevation ACS with less frequent intraluminal thrombi, but no significant difference in underlying plaque characteristics or clinical course.

Background:We are now facing rapid population aging in Japan, which will affect the actual situation of cardiovascular diseases. However, age-specific trends in the incidence and mortality of acute myocardial infarction (AMI) in Japan remain to be elucidated.

Methods and Results:We enrolled a total of 27,220 AMI patients (male/female 19,818/7,402) in our Miyagi AMI Registry during the past 30 years. We divided them into 4 age groups (≤59, 60–69, 70–79 and ≥80 years) and examined the temporal trends in the incidence and in-hospital mortality of AMI during 3 decades (1985–1994, 1995–2004 and 2005–2014). Throughout the entire period, the incidence of AMI steadily increased in the younger group (≤59 years in both sexes), while in the elderly groups (≥70 years in both sexes), the incidence significantly decreased during the last decade (all P<0.01). In-hospital cardiac mortality significantly decreased during the first 2 decades in elderly groups of both sexes (all P<0.01), whereas no further improvement was noted in the last decade irrespective of age or sex, despite improved critical care of AMI.

Conclusions:These results provide the novel findings that the incidence of AMI has been increasing in younger populations and decreasing in the elderly, and that improvement in the in-hospital mortality of AMI may have reached a plateau in all age groups in Japan.

Background:LV twist has a key role in maintaining left ventricular (LV) contractility during exercise. The purpose of this study was to investigate LV torsion instead of twist as a surrogate marker of peak oxygen uptake (peak V̇O₂) assessed by cardiopulmonary exercise testing (CPET) in patients with non-ischemic dilated cardiomyopathy (DCM).

Methods and Results:We evaluated 45 outpatients with DCM (50±12 years, 24% females) with 3D speckle-tracking electrocardiography prior to CPET. LV torsion, LV ejection fraction (EF), LV diastolic function, LV global longitudinal (GLS) and circumferential (GCS) strain were quantified. A reduced functional capacity (FC) was defined as a peak V̇O₂<20 mL/kg/min. LV torsion correlated most strongly with peak V̇O₂(r=0.76, P<0.001). LV torsion instead of twist was an independent predictor of peak V̇O₂(B: 0.59 to 0.71, P<0.001) in multivariable analyses. Impaired LV torsion <0.61 degrees/cm was able to predict a reduced FC with higher sensitivity and specificity (0.91 and 0.81; area under the curve (AUC): 0.88, P<0.001) than LV EF, GLS or GCS (AUC 0.64, 0.63 and 0.66; P<0.05 for differences in AUC).

Conclusions:Peak V̇O₂correlated more strongly with LV torsion than with LV diastolic function, LV EF, GLS or GCS. LV torsion had high accuracy in identifying patients with a reduced FC.

Background:Kawasaki disease (KD) is classified as a systemic vasculitis syndrome and QT interval dispersion (QTD) has been associated with cardiac involvement and disease activity in patients with cardiovasculitis. We examined whether baseline QTD could predict a response to intravenous immunoglobulin (IVIG) in KD.

Methods and Results:QTD was recorded in 86 patients with KD before IVIG, who were separated into IVIG responders (R group; n=62) and nonresponders (N group; n=24). The association between baseline QTD and response to IVIG was investigated, and the predictive response value was compared with conventional risk scores from Gunma and Kurume universities. Baseline-corrected QTDs with Bazett’s (QTbcD) and Fridericia’s (QTfcD) formulae were significantly increased in the N group (R group vs. N group: 31.6 [28.3, 44.0] ms vs. 66.6 [50.5, 76.3] ms and 27.4 [25.2, 39.1] ms vs. 55.2 [42.4, 66.3] ms, respectively, both P<0.001). Multiple logistic regression analysis revealed QTfcD as an independent predictor of a response to IVIG after adjustment for conventional scores (odds ratio: 1.133, 95% confidence interval: 1.061–1.210, P<0.001). Moreover, QTfcD provided incremental predictive value for IVIG nonresponders over Gunma score (increment in global χ²=25.46, P<0.001).

Conclusions:QTD was significantly associated with a response to IVIG in KD patients and may represent a useful identifier of IVIG nonresponders with high risk of coronary aneurysm.

Background:Percutaneous closure has replaced surgery for the majority of cases of secundum atrial septal defect (ASD). However, technological advances have made contemporary minimally invasive cardiac surgery (MICS) less invasive than conventional surgery. The aim of this study was to compare clinical outcomes of percutaneous closure of secundum ASD with those of contemporary MICS.

Methods and Results:We conducted a single-center retrospective study of 354 patients with ASD treated either with the Amplatzer Septal Occluder (134 patients) or MICS (220 patients) between 2000 and 2013. Success rates and the incidence of complications were compared. The success rates were 98% for percutaneous closure and 100% for MICS. There were no deaths in either group. Major complications occurred in 2 patients (1.5%) who underwent percutaneous closure and in 8 patients (3.6%) treated with MICS (P=0.16). Minor complications occurred in 15 patients (11.2%) who underwent percutaneous closure and in 46 patients (20.9%) treated with MICS (P=0.02). On multivariate analysis, MICS (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.46–5.81; P=0.002) and age >70 years (OR: 3.50, 95% CI: 1.40–8.75; P=0.008) were independent predictors of complications.

Conclusions:Percutaneous closure and MICS had high success rates without deaths. For ASD patients with a suitable anatomy, percutaneous closure can be considered as the first therapeutic option.

Background:The effect of balloon pulmonary angioplasty (BPA) on improvement in functional and hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) is known, but the quality of life (QoL) of patients treated with BPA has never been studied before.

Methods and Results:Twenty-five patients with inoperable or persistent CTEPH were enrolled in the study and filled out the 36-item Short Form (SF-36v2) questionnaire twice: prior to commencement of BPA treatment and after ≥3 BPA sessions. In addition WHO functional class, distance on the 6-min walk test (6MWT) and hemodynamic parameters such as right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were assessed. QoL improved significantly in all domains, except for physical pain. Improvement in RAP (10.5±3.4 vs. 6.2±2.2 mmHg; P<0.05), mPAP (51.7±10.6 vs. 35.0±9.1 mmHg; P<0.05), CI (2.2±0.5 vs. 2.5±0.4 L/min·m²; P=0.04), PVR (10.4±3.9 vs. 5.5±2.2 Wood units; P<0.05), functional class (96% vs. 20% in WHO class III and IV, P<0.05) and improvement in 6MWT distance (323±135 vs. 410±109 m; P<0.05) was observed. The only significant correlation was between the mental component summary score of QoL after completion of treatment and percentage improvement in the 6MWT (–0.404, P<0.05).

Conclusions:Alongside improvement in functional and hemodynamic parameters, BPA also provides significant improvement in QoL.

Background:The clinical significance of left ventricular (LV) diastolic function (DF) improvement after transcatheter aortic valve implantation (TAVI) is not fully elucidated. We sought to investigate the long-term clinical and hemodynamic effects of post-TAVI DF improvement and to identify its determinants.

Methods and Results:Clinical and serial echocardiographic data before and after TAVI were retrospectively reviewed together with measurement of mitral annular displacement (MAD) representing longitudinal myocardial function in 98 patients with severe aortic stenosis and ejection fraction >55%. DF grade was determined as 0–III according to the current guideline. Patients with ≥1-grade improvement in DF at 1 year (n=59, 60%) showed a better recovery of New York Heart Association functional class, plasma B-type natriuretic peptide level, stroke volume index, and averaged e’, and a greater decrease in systolic pulmonary artery pressure than those without DF improvement (all P<0.05). Coronary artery disease (odds ratio (OR), 0.30; 95% confidence interval (CI), 0.11–0.84; P=0.022) and averaged MAD (per 2.5 mm increase; OR, 4.11; 95% CI, 2.18–7.72; P<0.001) were predictors of post-TAVI DF improvement. An averaged MAD cutoff value of 10.7 mm discriminated cases of improvement with a sensitivity of 88% and specificity of 64%.

Conclusions:Post-TAVI DF improvement may be associated with preserved LV longitudinal function and when present may be accompanied by more favorable clinical and hemodynamic changes.

Background:Many microRNAs (miRNAs) have recently been shown to demonstrate critical roles in differentiation, proliferation and migration of vascular smooth muscle cells (VSMCs).

Methods and Results:In this study, a certain amount of miRNA expression in VSMCs was evaluated by real-time polymerase chain reaction, and it was found that microRNA-30e (miR-30e) was expressed more strongly than other common vascular well-expressed miRNAs in vitro. Subsequently, both a gain and loss of function study was performed in vitro and in vivo. It was found that miR-30e in VSMCs was strongly downregulated concomitantly with stimulation, and miR-30e inhibited VSMCs proliferation and migration both in vitro and in vivo. Furthermore, ubiquitin-conjugating enzyme E2I (Ube2i) was identified as the target gene of endogenous miR-30e by luciferase reporter assay, and it was confirmed that overexpression of miR-30e significantly reduced Ube2i and inhibited the phenotypic switch of VSMCs. Knockdown of Ube2i had an influence over the proliferation and migration of cultured VSMCs, as same as the miR-30e mimic did. Overexpression of miR-30e induced the apoptosis of VSMCs and deregulated the protein expression of IkBα, which is crucial for the NFκB signal pathway.

Conclusions:The results of this study indicated that miR-30e in VSMCs exerted an anti-atherosclerosis effect via inhibiting proliferation and migration, and promoting apoptosis of VSMCs. More specifically, it was demonstrated that miR-30e exhibited these effects on VSMCs partially through targeting Ube2i and downregulating the IκBα/NFκB signaling pathway.