小林 欣夫

INTRODUCTION: Ethanol infusion in the vein of Marshall (EIVOM) effectively creates a linear ablation lesion in the mitral isthmus (MI). However, data on the long-term success rates of MI ablation is limited. METHODS AND RESULTS: Our cohort consisted of 560 patients with nonparoxysmal atrial fibrillation (AF) who underwent an initial MI ablation. Ablations were performed by only radiofrequency (RF) in 384 (RF group) or by RF and EIVOM in 176 (EIVOM/RF group) patients; 5 ml anhydrous ethanol was used to perform EIVOM in advance of RF. Following EIVOM, RF pulses were delivered to the lateral MI line. Bidirectional MI block was fully achieved in 353/384 (92%) (First 318, Re-do 35) patinents in the RF group and 171/176 (97%) (First 128, Re-do 43) patients in the EIVOM/RF group (p = .09 in the first, p = .10 in the re-do ablation cases). In cases with complete MI line block, recurrent AF or atrial tachycardia was observed in 130/353 (37%) patients in the RF group and in 64/171 (37%) patients in the EIVOM/RF group (log-rank p = .12 in the first, and p = .30 in the re-do ablation cases). Of the total 560 patients, 123 proceeded to the subsequent ablation session. Reconduction across MI line block was observed in 39/80 (49%) patients in the RF group and 25/43 (58%) patients in the EIVOM/RF group (p = .32). CONCLUSION: EIVOM effectively ensures MI line block; however, the reconduction rate was similar between the two groups.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.

INTRODUCTION: Patients with cancer have an increased risk of cardiovascular disease including ischemic heart disease and vice versa. Anticancer drugs and radiotherapy are known to contribute to endothelial injury and vasospasm. However, the relations between vasospastic angina (VSA) and cancer or its treatment are poorly investigated. METHODS: A total of 786 patients underwent intracoronary acetylcholine (ACh) provocation tests to diagnose VSA. The positive ACh provocation test was defined as angiographic coronary artery spasm accompanied by chest pain and/or ischemic electrocardiographic changes. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. The impact of types of cancer, anticancer drugs, and radiotherapy on VSA was evaluated. RESULTS: Of 786 patients, 38 (4.8%) and 84 (10.7%) had active cancer and a history of cancer, respectively, and 401 (51.0%) were diagnosed as VSA. There was no significant difference in rates of positive ACh test among patients with active cancer, a history of cancer, and no cancer (39.5% vs. 57.1% vs. 50.9%, p = 0.20). Types of cancer and cancer treatment also had no impact on positive ACh provocation test. CONCLUSIONS: In this cross-sectional observational study, we did not find an association of active and a history of cancer with the diagnosis of VSA. Anticancer treatment including chemotherapy and radiotherapy was not significantly associated with positive ACh provocation test.

AIM: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear. METHODS: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR. RESULTS: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles. CONCLUSIONS: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

Uric acid, the end-product of purine metabolism in humans, is not only a cause of gout, but also may play roles in developing cardiovascular diseases such as hypertension, atrial fibrillation, chronic kidney disease, heart failure, coronary artery disease, and cardiovascular death. Several clinical investigations have reported serum uric acid as a predictive marker for cardiovascular outcomes. Although the causal relationship of hyperuricemia to cardiovascular diseases remains controversial, there has been a growing interest in uric acid because of the increased prevalence of hyperuricemia worldwide. This review article summarizes current evidence concerning the relation between hyperuricemia and cardiovascular diseases.

Sudden cardiac death is one of the leading causes of death in the older population. Compared with the general population, patients who experienced a myocardial infarction are four to six times more likely to experience sudden cardiac death. Though primary percutaneous coronary intervention considerably reduces mortality in patients who experienced a myocardial infarction, a non-negligible number of sudden cardiac deaths still occurs. Despite the high incidence rate of sudden cardiac deaths during the first month after myocardial infarction, prophylactic use of implantable cardioverter-defibrillators has so far failed to convey a survival benefit. Therefore, current clinical guidelines recommend that cardioverter-defibrillator implantation is contraindicated until 90 days after myocardial infarction. Wearable cardioverter-defibrillators were first approved for clinical use in 2002 and are currently considered as a bridge to therapy in patients with myocardial infarction with a reduced left ventricular ejection fraction in whom cardioverter-defibrillator implantation is temporarily not indicated. However, there is insufficient recognition among interventional cardiologists of the use of wearable cardioverter-defibrillators for preventing sudden cardiac death after myocardial infarction. Hence, we reviewed the evidence of the efficacy of wearable cardioverter-defibrillators used in patients following myocardial infarction to achieve better management of sudden cardiac death.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

AIMS: Little is known regarding factors that predict the occurrence of lethal ventricular arrhythmias (VAs) occurring after acute myocardial infarction (AMI). This observational cohort study aimed to identify factors that predicted lethal VAs during the late phase after AMI in patients with reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Data were collected from our AMI database regarding consecutive patients with an LVEF of ≤40% after AMI (January 2012 to July 2018). The 'late phase' was defined as ≥7 days after AMI onset, and the primary endpoint was defined as lethal VAs in the late phase. The study included 136 patients (82% men; mean age: 66 ± 13 years). The average LVEF at admission was 32.7 ± 8.2%. During a mean follow-up period of 20.7 months, 14 patients (10%) experienced lethal VAs, including ventricular fibrillation (n = 8) and sustained ventricular tachycardia (n = 10). Univariate analyses revealed that lethal VAs were predicted by age and LVEF at admission. Receiver operating characteristic curve analysis indicated that the optimal cut-off value was 23% for using the LVEF at admission to predict the primary endpoint (area under the curve: 0.77, P < 0.0001). Multivariable analysis also demonstrated that LVEF at admission was an independent predictor of the primary endpoint (risk ratio = 7.12, P = 0.001). CONCLUSIONS: Lethal VAs in the late phase are common in patients with AMI, and reduced LVEF and cardiac function at admission play a significant role in the risk stratification for future lethal VAs in this population.

Ly6Clow macrophages promote scar formation and prevent early infarct expansion after myocardial infarction (MI). Although CD4+ T cells influence the regulation of Ly6Clow macrophages after MI, the mechanism remains largely unknown. Based on the hypothesis that some molecule(s) secreted by CD4+ T cells act on Ly6Clow macrophages, we searched for candidate molecules by focusing on cytokine receptors expressed on Ly6Clow macrophages. Comparing the transcriptome between Ly6Chigh macrophages and Ly6Clow macrophages harvested from the infarcted heart, we found that Ly6Clow macrophages highly expressed the receptor for interleukin (IL)-21, a pleiotropic cytokine which is produced by several types of CD4+ T cells, compared with Ly6Chigh macrophages. Indeed, CD4+ T cells harvested from the infarcted heart produce IL-21 upon stimulation. Importantly, the survival rate and cardiac function after MI were significantly improved in IL-21-deficient (il21-/-) mice compared with those in wild-type (WT) mice. Transcriptome analysis of infarcted heart tissue from WT mice and il21-/- mice at 5 days after MI demonstrated that inflammation is persistent in WT mice compared with il21-/- mice. Consistent with the transcriptome analysis, the number of neutrophils and matrix metalloproteinase (MMP)-9 expression were significantly decreased, whereas the number of Ly6Clow macrophages and MMP-12 expression were significantly increased in il21-/- mice. In addition, collagen deposition and the number of myofibroblasts in the infarcted area were significantly increased in il21-/- mice. Consistently, IL-21 enhanced the apoptosis of Ly6Clow macrophages. Finally, administration of neutralizing IL-21 receptor Fc protein increased the number of Ly6Clow macrophages in the infarcted heart and improved the survival and cardiac function after MI. Thus, IL-21 decreases the survival after MI, possibly through the delay of wound healing by inducing the apoptosis of Ly6Clow macrophages.

BACKGROUND: Accurate segmentation of the coronary arteries with intravascular ultrasound (IVUS) is important to optimize coronary stent implantation. Recently, deep learning (DL) methods have been proposed to develop automatic IVUS segmentation. However, most of those have been limited to segmenting the lumen and vessel (i.e. lumen-intima and media-adventitia borders), not applied to segmenting stent dimension. Hence, this study aimed to develop a DL method for automatic IVUS segmentation of stent area in addition to lumen and vessel area. METHODS: This study included a total of 45,449 images from 1576 IVUS pullback runs. The datasets were randomly split into training, validation, and test datasets (0.7:0.15:0.15). After developing the DL-based system to segment IVUS images using the training and validation datasets, we evaluated the performance through the independent test dataset. RESULTS: The DL-based segmentation correlated well with the expert-analyzed segmentation with a mean intersection over union (± standard deviation) of 0.80 ± 0.20, correlation coefficient of 0.98 (95% confidence intervals: 0.98 to 0.98), 0.96 (0.95 to 0.96), and 0.96 (0.96 to 0.96) for lumen, vessel, and stent area, and the mean difference (± standard deviation) of 0.02 ± 0.57, -0.44 ± 1.56 and - 0.17 ± 0.74 mm2 for lumen, vessel and stent area, respectively. CONCLUSION: This automated DL-based IVUS segmentation of lumen, vessel and stent area showed an excellent agreement with manual segmentation by experts, supporting the feasibility of artificial intelligence-assisted IVUS assessment in patients undergoing coronary stent implantation.

BACKGROUND: It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL). PURPOSE: To investigate the difference between the patient background of both CAFL and AF in the non-elderly. METHODS: In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation. RESULTS: In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p<0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value <0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure. CONCLUSIONS: Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.

BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

AIMS: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. METHODS AND RESULTS: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002). CONCLUSIONS: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.

Aim: While previous studies have shown that the initial documented rhythm is associated with clinical outcomes in out-of-hospital cardiac arrest (OHCA), little is known about the difference in clinical outcomes between pulseless ventricular tachycardia (p-VT) and ventricular fibrillation (VF). Methods: From a nationwide, prospective population-based database of OHCA from 2011 to 2015, we selected bystander-witnessed adult patients who were not treated with a public automated external defibrillator. The outcomes examined were favorable 30-day neurological survival rates, 30-day survival rates, and prehospital return of spontaneous circulation (ROSC) rates. To determine the association of the initial documented rhythm with outcome, we used a logistic regression model while adjusting for patient factors and prehospital care-related factors. Results: A total of 19,594 bystander-witnessed OHCA patients who had a shockable rhythm were included: 454 (2.3%) were p-VT and 19,140 (97.7%) were VF. Compared to VF patients, p-VT patients were older, less likely to have a cardiogenic cause, and had shorter resuscitation-related time intervals (collapse to bystander cardiopulmonary resuscitation, collapse to emergency medical services contact, collapse to first ROSC, and first defibrillation to first ROSC). After adjustment for covariates, p-VT was associated with high favorable 30-day neurological survival rates (adjusted odds ratio [OR], 1.85; 95% confidence interval [CI], 1.30-2.64, p = 0.001), 30-day survival rates (adjusted OR, 1.41; 95% CI, 1.03-1.95, p = 0.037), and prehospital ROSC rates (adjusted OR, 1.90; 95% CI, 1.42-2.55, p < 0.001). Conclusion: In this study, patients with p-VT as the initial documented rhythm had significantly better outcomes than those with VF.

BACKGROUND: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. METHODS: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. RESULTS: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. CONCLUSION: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.

OBJECTIVES: This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan. BACKGROUND: Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy. METHODS: This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected. RESULTS: Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia. CONCLUSIONS: This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.

Objective Glycemic variability is being increasingly recognized as an early indicator of glucose metabolic disorder and may contribute to the development of diabetic vascular complications, such as coronary microvascular dysfunction. The present study sought to investigate the relationship between coronary microvascular function assessed by intracoronary thermodilution method and glycemic variability on a continuous glucose monitoring system (CGMS). Methods We prospectively enrolled 40 patients with or without known diabetes mellitus who had epicardial coronary artery disease referred for coronary angiography and were not treated with diabetic medications. Of these, two had a significant stenosis in the left main coronary artery and were therefore excluded from the analyses. In the end, 38 patients were equipped with a CGMS and underwent intracoronary physiological assessments in the unobstructed left anterior descending artery. The mean amplitude of glycemic excursion (MAGE) and standard deviation were calculated from the obtained CGMS data as indicators of glucose variability. Results Coronary flow reserve (CFR) was negatively correlated with MAGE (r=-0.328, p=0.044) and standard deviation (r=-0.339, p=0.037) on CGMS, while the index of microcirculatory resistance showed no such correlation. Multivariable linear regression analyses showed that MAGE on CGMS was significantly associated with CFR after adjusting for age, sex, fractional flow reserve and hemoglobin A1c. Conclusion Higher MAGE on CGMS was associated with reduced CFR in stable patients with coronary artery disease, suggesting a potential effect of glycemic variability on coronary microvascular flow regulation. A further study with a larger sample size needs to be conducted to confirm our findings.

Skin abnormalities are often indicative of cardiovascular diseases. Such a disease entity is called cardiocutaneous syndrome; however, the details regarding the involvement of bulla and nails remain largely unclear. A 49-year-old man with systemic bulla was admitted for heart failure. His bulla had previously been diagnosed as epidermolysis bullosa, but no known gene mutations for it had been identified. He had a triad of palmoplantar keratosis, curly and fine hair, and cardiomyopathy, which are characteristic of NAXOS-Carvajal syndrome. This case highlights the fact that bulla and brittle nails can accompany NAXOS-Carvajal syndrome, showing that these extra-cardiac findings can help identify otherwise overlooked serious cardiac conditions.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI4mm). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.

Percutaneous coronary intervention (PCI) for complex lesions is still technically demanding and is associated with less favorable procedural parameters such as lower success rate, longer procedural time, higher contrast volume and unexpected complications. Because the conventional angiographic analysis is limited by the inability to visualize the plaque information and the occluded segment, cardiac computed tomography has evolved as an adjunct to invasive angiography to better characterize coronary lesions to improve success rates of PCI. Adding to routine image reconstructions by coronary computed tomography angiography, the thin-slab maximum intensity projection method, which is a handy reconstruction technique on an ordinary workstation, could provide easy-to-understand images to reveal the anatomical characteristics and the lumen and plaque information simultaneously, and then assist to build an in-depth strategy for PCI. Especially in the treatment of chronic total occlusion lesion, these informations have big advantages in the visualization of the morphologies of entry and exit, the occluded segment and the distribution of calcium compared to invasive coronary angiography. Despite of the additional radiation exposure, contrast use and cost for cardiac computed tomography, the precise analysis of lesion characteristics would consequently improve the procedural success and prevent the complication in complex PCI.

Over the past 40 years, the safety and efficacy of percutaneous coronary intervention has dramatically improved by overcoming several challenges. The introduction of drug-eluting stent (DES) in particular was a major breakthrough in interventional cardiology. Compared to bare-metal stents, first-generation DES (G1-DES) has dramatically reduced the rates of in-stent restenosis and subsequent target lesion revascularization. However, major safety concerns surrounding stent thrombosis (ST) emerged with G1-DES in clinical practice as a result of the high incidences of death, myocardial infarction, and repeat revascularization associated with ST. To overcome these limitations, second-generation DES (G2-DES) has been developed with an improved stent platform with thinner strut and biocompatible durable or biodegradable polymers. Indeed, G2-DES, when compared with G1-DES, has improved clinical outcomes by reducing the risk of late thrombotic events while maintaining anti-restenotic efficacy, whereas ST still occurs, even with the use of G2-DES. This review gives an overview of pathophysiology, risk factors, and outcomes of ST after DES implantation. Additionally, we discuss the management and prevention of ST.

The ISCHEMIA was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, non-invasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized COURAGE trial did not support the plausible concept. Although the FAME 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of non-invasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.

BACKGROUND: High platelet reactivity (HPR) is associated with subsequent thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ABCD-GENE score was developed to identify patients at risk for HPR, incorporating both clinical and genetic factors. However, this score was derived and validated in mostly Caucasian subjects and it has not been validated in an East Asian population. METHOD: Individual patient data from 4 prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay on clopidogrel and genotyping of CYP2C19 was performed after PCI. Study populations included patients with general stable coronary artery disease, hemodialysis, age ≥75 and/or body weight <50 kg, and acute coronary syndrome. VerifyNow P2Y12 reactivity units >208 was defined as HPR. RESULTS: Of 184 patients, 111 (60%) had HPR on clopidogrel. In the receiver operating characteristics curve analyses, the ABCD-GENE score significantly predicted HPR on clopidogrel (AUC 0.78, best cut-off value 9, p < 0.001). Across the 4 studies and their combinations, the diagnostic ability and cut-off values of ABCD-GENE score for HPR on clopidogrel were consistent. CONCLUSIONS: The ABCD-GENE score had significant and moderate diagnostic ability for HPR on clopidogrel in Japanese patients undergoing PCI. The predictivity was consistent across a broad spectrum of patient populations, suggesting the applicability of this novel scoring system in clinical practice worldwide.