藤田 英雄

In-stent restenosis with neoatherosclerosis has been known as the predictor of target lesion revascularization (TLR) after percutaneous coronary intervention. However, the impact of in-stent calcification (ISC) alone on clinical outcomes remains unknown since neoatherosclerosis by optical coherence tomography includes in-stent lipid and calcification. We aimed to assess the effect of ISC on clinical outcomes and clinical differences among different types of ISC. We included 126 lesions that underwent optical coherence tomography-guided percutaneous coronary intervention and divided those into the ISC group (n = 38) and the non-ISC group (n = 88) according to the presence of ISC. The cumulative incidence of clinically driven TLR (CD-TLR) was compared between the ISC and non-ISC groups. The impact of in-stent calcified nodule and nodular calcification on CD-TLR was evaluated using the Cox hazard model. The incidence of CD-TLR was significantly higher in the ISC group than in the non-ISC group (p = 0.004). In the multivariate Cox hazard model, ISC was significantly associated with CD-TLR (hazard ratio [HR] 3.58, 95% confidence interval [CI] 1.33 to 9.65, p = 0.01). In-stent calcified nodule/nodular calcification and in-stent nodular calcification alone were also the factors significantly associated with CD-TLR (HR 3.34, 95%CI 1.15 to 9.65, p = 0.03 and HR 5.21, 95%CI 1.82 to 14.91, p = 0.002, respectively). ISC without in-stent calcified nodule/nodular calcification, which was defined as in-stent smooth calcification, was not associated with CD-TLR. In conclusion, ISC was associated with a higher rate of CD-TLR. The types of calcifications that led to a high rate of CD-TLR were in-stent calcified nodule/nodular calcification and in-stent nodular calcification alone but not in-stent smooth calcification. In-stent calcified nodule and nodular calcification should be paid more attention.

Rotational atherectomy (RA) is technically more difficult in a diffuse calcified lesion than in a focal calcified lesion. We hypothesized that taking a halftime can be another option for RA to the diffuse calcified lesions. Halftime was defined as at least one long break during RA, in which an operator pulled out the Rotablator system from the guide catheter before crossing the lesion. This study aimed to compare the complications between RA with and without halftime. We included 177 diffuse long severely calcified lesions (lesion lengths ≥ 30 mm) that required RA, and divided those lesions into a halftime group (n = 29) and a no-halftime group (n = 148). The primary outcome was periprocedural myocardial infarction (MI). The reference diameter was smaller in the halftime group than in the no-halftime group [1.82 (1.70-2.06) mm versus 2.17 (1.89-2.59) mm, p = 0.002]. The total run time was longer in the halftime group than in the non-halftime group [133.0 (102.0-223.0) seconds versus 71.5 (42.0-108.0) seconds, p < 0.001]. Although creatinine kinase (CK) and CK-myocardial band (MB) was significantly higher in the halftime group than in the no-halftime group [CK: 156 (97-308) U/L versus 99 (59-216) U/L, p = 0.021; CK-MB: 15 (8-24) U/L versus 5 (3-15) U/L, p < 0.001], periprocedural MI was not observed in the halftime group. In conclusion, periprocedural MI was not observed in RA with halftime. This preliminary study suggests that halftime RA may be a safe option for diffuse severely calcified lesions.

OBJECTIVE: Making the diagnosis of sarcopenia is not always easy and this is especially true for those with cardiovascular disease. The purpose of this study is to investigate whether it is possible to diagnose sarcopenia by using ultrasound-guided measurements of anterior femoral muscle thickness. METHODS: We investigated the utility of ultrasound-guided measurements of anterior femoral muscle thickness in 1075 hospitalized patients with cardiovascular disease (675 men). As a comparison, sarcopenia was assessed by skeletal muscle mass index using bioelectrical impedance analysis and the Asia Working Group for Sarcopenia criteria. RESULTS: When the receiver operating characteristic curve using muscle thickness was examined, we found this could be used to make the diagnosis of sarcopenia (men: cutoff value 2.425 cm, area under the curve 0.796; women: cutoff value 1.995 cm, area under the curve 0.746). The prevalence of sarcopenia according to the criteria with skeletal muscle mass index was 34.2% in men and 51.8% in women, while its prevalence according to the cutoff value of muscle thickness was 29.2% in men and 36.7% in women. CONCLUSION: Ultrasound-guided measurement of the anterior femoral muscle thickness is a simple and useful method to help make the diagnosis of sarcopenia in patients with cardiovascular disease.

AIMS: Bleeding complications are often observed in patients with ST-segment elevation myocardial infarction (STEMI). Although the Japanese version of the high bleeding risk criteria (J-HBR) were established, it has not been sufficiently validated in patients with STEMI. This retrospective study aims to examine whether J-HBR is associated with cardiovascular and bleeding events in patients with STEMI. METHODS: We included 897 patients with STEMI and divided them into the J-HBR group (n=567) and the non-J-HBR group (n=330). The primary endpoint was the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction, ischemic stroke, and systemic embolism. Another primary endpoint was total bleeding events defined as type 3 or 5 bleeding events as defined by the Bleeding Academic Research Consortium . RESULTS: During the median follow-up duration of 573 days, 187 MACE and 141 total bleeding events were observed. The Kaplan-Meier curves showed that MACE and total bleeding events were more frequently observed in the J-HBR group than in the non-J-HBR group (p＜0.001). Multivariate Cox hazard analysis revealed that after controlling for multiple confounding factors, the J-HBR group was significantly associated with MACE (hazard ratio [HR] 4.676, 95% confidence interval (CI) 2.936-7.448, p＜0.001) and total bleeding events (HR 6.325,95% CI 3.376-11.851, p＜0.001). CONCLUSIONS: J-HBR is significantly associated with MACE and total bleeding events in patients with STEMI. This study validated J-HBR as a risk marker for bleeding events and suggests J-HBR as a potential risk marker for MACE in patients with STEMI.

OBJECTIVE: This study aimed to investigate the association between heart failure (HF) severity measured based on brain natriuretic peptide (BNP) levels and future bleeding events after percutaneous coronary intervention (PCI). BACKGROUND: The Academic Research Consortium for High Bleeding Risk presents a bleeding risk assessment for antithrombotic therapy in patients after PCI. HF is a risk factor for bleeding in Japanese patients. METHODS: Using an electronic medical record-based database with seven tertiary hospitals in Japan, this retrospective study included 7160 patients who underwent PCI between April 2014 and March 2020 and who completed a 3-year follow-up and were divided into three groups: no HF, HF with high BNP level and HF with low BNP level. The primary outcome was bleeding events according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. The secondary outcome was major adverse cardiovascular events (MACE). Furthermore, thrombogenicity was measured using the Total Thrombus-Formation Analysis System (T-TAS) in 536 consecutive patients undergoing PCI between August 2013 and March 2017 at Kumamoto University Hospital. RESULTS: Multivariate Cox regression showed that HF with high BNP level was significantly associated with bleeding events, MACE and all-cause death. In the T-TAS measurement, the thrombogenicity was lower in patients with HF with high BNP levels than in those without HF and with HF with low BNP levels. CONCLUSIONS: HF with high BNP level is associated with future bleeding events, suggesting that bleeding risk might differ depending on HF severity.

Mechanical complication (MC) is a rare but serious complication in patients with ST-segment elevation myocardial infarction (STEMI). Although several risk factors for MC have been reported, a prediction model for MC has not been established. This study aimed to develop a simple prediction model for MC after STEMI. We included 1717 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Of 1717 patients, 45 MCs occurred after primary PCI. Prespecified predictors were determined to develop a tentative prediction model for MC using multivariable regression analysis. Then, a simple prediction model for MC was generated. Age ≥ 70, Killip class ≥ 2, white blood cell ≥ 10,000/µl, and onset-to-visit time ≥ 8 h were included in a simple prediction model as "point 1" risk score, whereas initial thrombolysis in myocardial infarction (TIMI) flow grade ≤ 1 and final TIMI flow grade ≤ 2 were included as "point 2" risk score. The simple prediction model for MC showed good discrimination with the optimism-corrected area under the receiver-operating characteristic curve of 0.850 (95% CI: 0.798-0.902). The predicted probability for MC was 0-2% in patients with 0-4 points of risk score, whereas that was 6-50% in patients with 5-8 points. In conclusion, we developed a simple prediction model for MC. We may be able to predict the probability for MC by this simple prediction model.

BACKGROUND: Left heart abnormalities are risk factors for heart failure. However, echocardiography is not always available. Electrocardiograms (ECGs), which are now available from wearable devices, have the potential to detect these abnormalities. Nevertheless, whether a model can detect left heart abnormalities from single Lead I ECG data remains unclear.Methods and Results: We developed Lead I ECG models to detect low ejection fraction (EF), wall motion abnormality, left ventricular hypertrophy (LVH), left ventricular dilatation, and left atrial dilatation. We used a dataset comprising 229,439 paired sets of ECG and echocardiography data from 8 facilities, and validated the model using external verification with data from 2 facilities. The area under the receiver operating characteristic curves of our model was 0.913 for low EF, 0.832 for wall motion abnormality, 0.797 for LVH, 0.838 for left ventricular dilatation, and 0.802 for left atrial dilatation. In interpretation tests with 12 cardiologists, the accuracy of the model was 78.3% for low EF and 68.3% for LVH. Compared with cardiologists who read the 12-lead ECGs, the model's performance was superior for LVH and similar for low EF. CONCLUSIONS: From a multicenter study dataset, we developed models to predict left heart abnormalities using Lead I on the ECG. The Lead I ECG models show superior or equivalent performance to cardiologists using 12-lead ECGs.

OBJECTIVE: Although the clinical outcomes for patients with ST-elevation myocardial infarction (STEMI) have improved significantly, some patients still experience poor clinical outcomes. The available risk classifications focus on the short-term outcomes, and it remains important to find high-risk features among patients with STEMI. In Japan, the 200 m walk electrocardiogram (ECG) test is widely performed before discharge. The purpose of this study was to investigate the association between the excessive increase in systolic blood pressure (SBP) following a 200 m walk and the long-term clinical outcomes in patients with STEMI. METHODS: We included 680 patients with STEMI and divided those into an excessive increase in SBP group (n = 144) and a non-excessive increase in SBP group (n = 536) according to the SBP increase after a 200 m walk ECG test. We defined an excessive increase in SBP as SBP ≥ 20 mmHg either just after or 3 min after a 200 m walk ECG test. The primary endpoint consisted of major cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction, readmission for heart failure, and ischemia-driven target vessel revascularization. RESULTS: The median follow-up duration was 831 days. MACE was more frequently observed in the excessive increase in SBP group (24.3%) than in the non-excessive increase in SBP group (15.1%). Multivariate Cox hazard analysis revealed that the excessive increase in SBP was significantly associated with MACE (HR 1.509, 95% CI: 1.005-2.267, p = 0.047) after controlling for multiple confounding factors. CONCLUSION: An excessive increase in SBP after the 200 m walk ECG test was significantly associated with MACE in patients with STEMI. The 200 m walk ECG test is simple and low-cost, but may help to identify high-risk patients with STEMI.

BACKGROUND: Although major guidelines recommend the routine introduction of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers for patients with ST-segment elevation myocardial infarction (STEMI), evidence regarding the target blood pressure (BP) or pulse rate (PR) at hospital discharge is sparse. This retrospective study aimed to compare the clinical outcomes in patients with STEMI between those with good BP and PR control and those with poor BP or PR control. METHODS: We included 748 patients with STEMI who received both ACE inhibitors/ARBs and beta-blockers at hospital discharge, and divided them into a good control group (systolic BP ≤140 mmHg and PR ≤80 bpm, n = 564) and a poor control group (systolic BP >140 mmHg or PR >80 bpm, n = 184). The primary endpoint was major cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction, and re-admission for heart failure. RESULTS: During the median follow-up duration of 568 days, a total of 119 MACE were observed. The Kaplan-Meier curves showed that MACE were more frequently observed in the poor control group (p = 0.009). In the multivariate Cox hazard analysis, the good control group was inversely associated with MACE (HR 0.656, 95 % CI: 0.444-0.968, p = 0.034) after controlling for multiple confounding factors. CONCLUSIONS: The good control of systolic BP and PR at discharge was inversely associated with long-term adverse events in STEMI patients treated with both ACE inhibitors/ARBs and beta blockers. This study suggests the importance of titration of ACE inhibitors/ARBs and beta-blockers for better clinical outcomes in patients with STEMI.

The concept of lifetime management has not been discussed in the field of percutaneous coronary intervention (PCI), because the durability of drug-eluting stent (DES) is considered to be long enough for most patients. Furthermore, even if in-stent restenosis occurs, the treatment for in-stent restenosis is simple in most cases. On the other hand, the long-term clinical outcomes after DES implantation are worse in severely calcified coronary lesions than in non-calcified lesions. Moreover, the treatment for in-stent calcified restenosis or restenosis due to stent underexpansion is not simple. The concept of lifetime management of severely calcified lesions may be necessary like that of aortic stenosis. Recently, several algorithms have been published in PCI to severely calcified lesions, partly because of the emergence of IVL. These algorithms focus on the selection of cracking and debulking devices for the preparation of stenting. However, the optimal stent expansion does not guarantee the long-term patency, when the target lesion includes calcified nodules. Stent restenosis due to calcified nodules is difficult to manage. In this review article, we propose the algorithm for severely calcified lesions focused on the shape of calcification. We do not need to hesitate stenting when multiple cracks on circumferential calcification are observed by intravascular imaging devices. However, DCB may be an option as final device in some situations, when lifetime management of severely calcified lesions is considered.

BACKGROUND: Recently, the nutritional status of patients has drawn attention in an aging society. Early studies have reported that nutritional status is related to long-term outcomes in patients with acute myocardial infarction (AMI). However, it is not necessarily simple to evaluate the nutritional status of patients with AMI. We hypothesized that appetite before discharge can be a predictor for long-term adverse cardiovascular events in patients with AMI. This retrospective study aimed to investigate whether appetite is related to long-term adverse outcomes in patients with AMI. METHODS: This study included 1006 patients with AMI, and divided them into the good appetite group (n = 860) and the poor appetite group (n = 146) according to the percentage of the dietary intake on the day before discharge. Major adverse cardiac events (MACE), which were defined as a composite of all-cause death, non-fatal MI, and re-admission for heart failure, were set as the primary outcome. RESULTS: The median follow-up duration was 996 days, and a total of 243 MACE was observed during the study period. MACE was more frequently observed in the poor appetite group than in the good appetite group (42.5% versus 21.0%, p < 0.001). In the multivariate COX hazard model, poor appetite was significantly associated with MACE (Hazard ratio 1.698, 95% confidence interval 1.243-2.319, p < 0.001) after controlling for multiple confounding factors. CONCLUSION: Appetite at the time of discharge was significantly associated with long-term clinical outcomes in patients with AMI. Patients with poor appetite should be carefully followed up after discharge from AMI.

Objective Patients with acute myocardial infarction (AMI) often have peripheral artery disease (PAD). It is well known that the long-term clinical outcomes of AMI are worse in patients with a low ankle-brachial index (ABI) than in patients with a preserved ABI. Unlike ABI, the association between the inter-arm blood pressure difference (IABPD) and clinical outcomes in patients with AMI has not yet been established. This retrospective study examined whether or not the IABPD is associated with long-term clinical outcomes in patients with AMI. Methods We included 979 patients with AMI and divided them into a high-IABPD group (IABPD ≥10 mmHg, n=31) and a low-IABPD group (IABPD <10 mmHg, n=948) according to the IABPD measured during hospitalization for AMI. The primary endpoint was the all-cause mortality rate. Results During a median follow-up duration of 694 days (Q1, 296 days; Q3, 1,281 days), 82 all-cause deaths were observed. Kaplan-Meier curves showed that all-cause death was more frequently observed in the high-IABPD group than in the low-IABPD group (p<0.001). A multivariate Cox hazard analysis revealed that a high IABPD was significantly associated with all-cause death (hazard ratio 2.061, 95% confidence interval 1.012-4.197, p=0.046) after controlling for multiple confounding factors. Conclusion A high IABPD was significantly associated with long-term all-cause mortality in patients with AMI. Our results suggest the usefulness of the IABPD as a prognostic marker for patients with AMI.

Background and Objectives: Extracellular water is increased in patients with edema, such as those with chronic heart failure, and it is difficult to assess skeletal muscle mass with the skeletal muscle mass index when extracellular water is high. We investigated the relationship between phase angle and physical function, nutritional indices, and sarcopenia in patients with cardiovascular diseases, including chronic heart failure. Methods and Study Design: In 590 patients with cardiovascular diseases (372 men), handgrip strength, gait speed, and anterior mid-thigh muscle thickness by ultrasound were measured, and the skeletal muscle mass index, phase angle, and the extracellular water: total body water ratio were measured with a bioelectrical impedance analyzer, and presence of sarcopenia was evaluated. Results: Phase angle, but not the skeletal muscle mass index, was correlated with serum albumin (r = 0.377, p < 0.001) and hemoglobin values in women. Multivariate regression analysis showed that at the extracellular water: total body water ratio below 0.4, both phase angle and skeletal muscle mass index were independent determinants of handgrip strength and log mid-thigh muscle thickness in men, after adjustment for age and presence of chronic heart failure. In contrast, for the ratio of 0.4 or greater, after adjustment for age and presence of chronic heart failure, phase angle was a stronger independent determinant of handgrip strength and log mid-thigh muscle thickness than the skeletal muscle mass index in men. Conclusions: Phase angle is a good marker of muscle wasting and malnutrition in patients with cardiovascular disease, including chronic heart failure.

BACKGROUND: Many techniques and concepts have been developed in the field of percutaneous coronary intervention to chronic total occlusion (CTO). Parallel wire technique (PWT) is still an important technique in antegrade approach. The purpose of this study was to identify the determinants of successful PWT in coronary CTO. METHODS: We reviewed consecutive 451 CTO lesions that were treated with PCI in our medical center. The overall success rate of PCI to CTO during the study period was 92.2 % (416/451). Of 451 CTO lesions, we excluded 333 CTO lesions in which PTW was not performed. We included 118 CTO lesions in which PWT was performed, and divided them into the successful PWT group (n = 65) and the unsuccessful PWT group (n = 53) according to the procedure success of PWT. Multivariate logistic regression analysis were performed to find the determinants of successful PWT. RESULTS: The prevalence of the sufficient clarity of CTO exit site was significantly higher in the successful PWT group (46.2 %) than in the unsuccessful PWT group (11.3 %) (p < 0.01). Multivariate logistic regression analysis revealed that the J-CTO score was inversely associated with successful PWT (OR 0.66, 95 % CI 0.44-0.99, P = 0.04), whereas the sufficient clarity of CTO exit site was associated with successful PWT (OR 5.16, 95 % CI 1.75-15.20, P < 0.01). CONCLUSIONS: The J-CTO score was inversely associated with successful PWT, whereas the sufficient clarity of CTO exit site was associated with successful PWT. The low J-CTO score and the sufficient clarity of CTO exit site may be the determinants of successful PWT.

OBJECTIVE: This study aimed to compare the contribution of 18F-fluorodepxyglucose (FDG) positron (PET)/ computed tomography (CT) acquisition of early and delayed scans in patients with cardiac sarcoidosis (CS). METHODS: Twenty-three patients with CS (median age: 69 years; 11 women) were retrospectively evaluated using dual-phase FDG PET/CT. All patients were instructed to consume a low-carbohydrate diet followed by fasting for 18 h before FDG injection to reduce physiological myocardial uptake. PET/CT was acquired at 60 min (early) and 100 min (delayed) after FDG administration. Focal and focal on diffuse uptake on visual analysis was considered positive for CS. A semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) of the cardiac lesion and the mean SUV (SUVmean) of the blood pool. RESULTS: Significant myocardial FDG uptake was observed in 21 patients (91.3%) in the early acquisition group and in 23 patients in the delayed scan group (100%). Compared to the early scan, the delayed scan showed a significantly higher SUVmax of the cardiac lesion [median, 4.0; IQR (interquartile range, 2.9 to 7.0) vs. 5.8 (IQR 3.7 to 10.1); P = 0.0030] and a significantly lower SUVmean of blood pool [median, 1.3 (IQR, 1.2 to 1.4) vs. 1.1 (IQR, 0.9 to 1.2); P < 0.0001]. CONCLUSION: Delayed FDG PET/CT acquisition improves detection accuracy in patients with CS compared to early scans with washout of the blood pool activity. Therefore, it can contribute to a more accurate assessment of CS.

Recently, there has been a growing interest in the concept of complex and high-risk intervention in indicated patients (CHIP). In our previous studies, we defined the three CHIP components (complex PCI, patient factors, and complicated heart disease), and introduced a novel stratification based on patient factors and/or complicated heart disease. We divided patients undergoing complex PCI into the definite CHIP, the possible CHIP, and the non-CHIP groups. Definite CHIP was defined as complex PCI for patients with both patient factors and complicated heart disease, and possible CHIP was defined as complex PCI for patients with either patient factors or complicated heart disease. Of note, even if a patient has both patients' factors and complicated heart disease, non-complex PCI is not a CHIP-PCI. In this review article, we discussed the determinants of complications in CHIP-PCI, long-term outcomes after CHIP-PCI, mechanical circulatory support devices for CHIP-PCI, and the goal of CHIP-PCI. Although CHIP-PCI attracts rising attention in contemporary PCI, clinical studies that investigate the clinical implications of CHIP-PCI are still sparse. Further studies are warranted to optimize CHIP-PCI.

Serious complications including vessel perforation may occur during rotational atherectomy (RA) to left circumflex (LCX) ostial lesions. In fact, if perforation occurs around LCX ostium, bailout procedures including deployment of covered stents may cause fatal ischemia in the territory of left anterior descending artery, which results in broad anterior acute myocardial infarction and subsequent death. In this review article, we described tips and tricks for RA to LCX ostial lesions. First, we should cautiously decide the indication for RA to LCX ostial lesions, because there are several reasons to avoid RA to LCX ostial lesions. Before procedures, we should estimate the difficulty of RA to LCX ostial lesions, which is mainly determined by the combination of the bifurcation angle and the severity of stenosis. Thus, the combination of the large bifurcation angle and the tight stenosis makes RA to LCX ostial lesions most difficult. Appropriate position of guide catheter and RotaWire is a key to successful RA to LCX ostial lesions. Differential cutting is an essential concept for RA to LCX ostial lesions. However, since there is no guarantee that differential cutting always works, small burr (≤ 1.5 mm) would be a safe choice as initial burr for RA to LCX ostial lesions.

51歳女性。Preexcited tachycardia(PT)に対し,アブレーションを行った。心房刺激で房室伝導の延長とともにQRS幅が増大し,広義のMahaim束の存在が示唆された。ATP投与により(AH)ブロックに遅れてMahaim束がブロックされたため,nodoventricular/nodofascicular pathwayは否定的であった。心房刺激で誘発されたPTのQRS幅は連続的に変化し,AA間隔と逆相関した。心室刺激で心房捕捉することなく頻拍は停止し,心房頻拍を除外した。Mahaim束を介したantidromic reciprocating tachycardia(ART)とbystanderのMahaim束を伴うAVNRTとの鑑別に苦慮したが,頻拍中と洞調律中のHis束の極性が反転しており,前者の可能性が高いと判断した。洞調律中にHis束に先行する右脚電位を認め,本Mahaim束はatriofascicular pathwayであり,QRS幅と左軸偏位の程度が正相関することから,QRS幅と頻拍周期の変化は,心室内伝導のターンアラウンドとなる刺激伝導路末端でのブロック位置の変化に伴うものと推察した。Mahaim束離断後,頻拍の再発を認めていない。Mahaim束を介し頻拍周期とQRS波形の経時的変化を認めた稀有なART症例を経験した。(著者抄録)

Recently, there has been a growing interest in complex and high-risk intervention in indicated patients (CHIP) in the contemporary percutaneous coronary intervention (PCI). CHIP is composed of the following 3 factors: (1) patient factors, (2) complicated heart disease, and (3) complex PCI. However, there are few studies that investigated the long-term outcomes of CHIP-PCI. The purpose of this study was to compare the incidence of long-term major adverse cardiovascular events (MACEs) among the definite CHIP, possible CHIP, and non-CHIP groups in complex PCI. We included 961 patients and divided them into the definite CHIP (n = 129), the possible CHIP (n = 369), and the non-CHIP groups (n = 463). During the median follow-up duration of 573 days (quartile 1:226 days to quartile 3:1,165 days), a total of 189 MACE were observed. The incidence of MACE was highest in the definite CHIP group, followed by the possible CHIP group, and lowest in the non-CHIP group (p = 0.001). Definite CHIP (vs non-CHIP: odds ratio 3.558, 95% confidence interval 2.249 to 5.629, p <0.001) and possible CHIP (vs non-CHIP: odds ratio 2.260, 95% confidence interval 1.563 to 3.266, p <0.001) were significantly associated with MACE after controlling for confounding factors. Among CHIP factors, active malignancy, pulmonary disease, hemodialysis, unstable hemodynamics, left ventricular ejection fraction, and valvular disease were significantly associated with MACE. In conclusion, the incidence of MACE in complex PCI was highest in the definite CHIP group, followed by the possible CHIP group, and lowest in the non-CHIP group. The concept of CHIP should be recognized to predict the long-term MACE in patients who undergo complex PCI.

Peak C-reactive protein (CRP) levels following ST-segment elevation myocardial infarction (STEMI) are associated with left ventricular thrombus formation or cardiac rupture. However, the impact of peak CRP on long-term outcomes in patients with STEMI is not completely understood. The purpose of this retrospective study was to compare the long-term all-cause death after STEMI between patients with and without high peak CRP levels. We included 594 patients with STEMI, and divided them into the high CRP group (n = 119) and the low-moderate CRP group (n = 475) according to the quintile of peak CRP levels. The primary endpoint was all-cause death after the discharge of the index admission. The mean peak CRP level was 19.66 ± 5.14 mg/dL in the high CRP group, whereas that was 6.43 ± 3.86 mg/dL in the low-moderate CRP group (p < 0.001). During the median follow-up duration of 1045 days (Q1 284 days, Q3 1603 days), a total of 45 all-cause deaths were observed. The Kaplan-Meier curves showed that all-cause death was more frequently observed in the high CRP group than in the low-moderate CRP group (p = 0.002). The multivariate Cox hazard analysis revealed that high CRP was significantly associated with all-cause death (hazard ratio 2.325, 95% confidence interval 1.246-4.341, p = 0.008) after controlling for confounding factors. In conclusion, high peak CRP was significantly associated with all-cause death in patients with STEMI. Our results suggest that peak CRP may be useful to stratify patients with STEMI for the risk of future death.

BACKGROUND: Acute ischemic stroke (AIS) is a rare but critical complication following ST-elevation myocardial infarction (STEMI). The risk of AIS or transient ischemic attack (TIA) may be amplified by invasive procedures, including primary percutaneous coronary intervention (PCI). This study aimed to investigate the factors associated with in-hospital AIS/TIA in patients with STEMI who required primary PCI. METHODS: We included 941 STEMI patients who underwent primary PCI and divided them into an AIS/TIA group (n = 39) and a non-AIS/TIA group (n = 902), according to new-onset AIS/TIA. The primary interest was to find the factors associated with AIS/TIA by multivariate logistic regression analysis. We also compared clinical outcomes between the AIS/TIA and non-AIS/TIA groups. RESULTS: The incidence of in-hospital deaths was significantly higher in the AIS/TIA group (46.2%) than in the non-AIS/TIA group (6.3%) (p < 0.001). Multivariate analysis revealed that cardiogenic shock (OR 3.228, 95% CI 1.492-6.986, p = 0.003), new-onset atrial fibrillation (AF) (OR 2.280, 95% CI 1.033-5.031, p = 0.041), trans-femoral approach (OR 2.336, 95% CI 1.093-4.992, p = 0.029), use of ≥4 catheters (OR 3.715, 95% CI 1.831-7.537, p < 0.001), and bleeding academic research consortium (BARC) type 3 or 5 bleeding (OR 2.932, 95% CI 1.256-6.846, p = 0.013) were significantly associated with AIS/TIA. CONCLUSION: In STEMI patients with primary PCI, new-onset AIS/TIA was significantly associated with cardiogenic shock, new-onset AF, trans-femoral approach, the use of ≥4 catheters, and BARC type 3 or 5 bleeding. We should recognize these modifiable and unmodifiable risk factors for AIS/TIA in the treatment of STEMI.

Although there are several books or manuscripts regarding how to prepare scientific manuscripts, the literatures focusing on the preparation of the revised manuscript are sparse. The process of revisions may be different between experimental medicine and clinical medicine. In this review, we summarize the tips for the revised manuscript in clinical medicine. When the authors receive the invitation of revisions from the editors, the authors should try to resubmit the revised manuscript at the earliest convenience. In the preparation of the rebuttal letter, the authors must respect the reviewers' effort for their manuscript. It is important for the authors to make the reviewers feel that the authors take a best effort to verify the reviewer's request.

PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors. PATIENTS AND METHODS: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤7.5% and peak creatinine phosphokinase <2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups. RESULTS: The DPP-4 activity (∆-509.5 ± 105.7 vs ∆32.8 ± 53.4 μU/mL) and SDF-1α levels (∆-695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆-0.3% ± 2.9%, P=0.006). CONCLUSION: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.

BACKGROUND: Epidemiological studies reported that acute myocardial infarction (AMI) occurs more often in winter season or days with low temperatures. However, most of these studies did not distinguish ST-elevation myocardial infarction (STEMI) from AMI. The purpose of this study was to investigate the relationship between temperature and the occurrence of STEMI. METHODS: We reviewed all daily temperature in Saitama City between January 2015 and December 2021 (2557 days) and divided them into days in which our institution received STEMI (days with STEMI) and days in which our institution did not receive STEMI (days without STEMI). RESULTS: The daily maximum temperature was significantly lower in days with STEMI than in days without STEMI [20.0 °C (68.0 °F) versus 21.2 °C (70.2 °F), p = 0.001]. The maximum temperature was significantly lower in days with STEMI than in days without STEMI in the elderly [19.9 °C (67.8 °F) versus 21.1 °C (70.0 °F), p = 0.003], whereas this trend was weaker in the non-elderly [20.2 °C (68.4 °F) versus 20.9 °C (69.6 °F), p = 0.171]. Furthermore, the maximum temperature was significantly lower in days with STEMI than in days without STEMI in male [20.0 °C (68.0 °F) versus 21.1 °C (70.0 °F), p = 0.002], whereas this trend was weaker in females [20.0 °C (68.0 °F) versus 20.9 °C (69.6 °F), p = 0.169]. CONCLUSIONS: The daily temperatures were significantly lower in days with STEMI than in days without STEMI, and this relationship was pronounced in elderly or male patients.

AIMS: Complex and high-risk intervention in indicated patients (CHIP) is an emerging concept in the contemporary percutaneous coronary intervention (PCI). CHIP is known to consist three factors, namely, (1) patient factors, (2) complicated heart disease, and (3) complex PCI. However, it remains unclear whether additional CHIP factors further increase the incidence of complications in complex PCI. Thus, in this study, we aim to compare the incidence of complications among definite CHIP, possible CHIP, and non-CHIP in terms of complex PCI and to further investigate the association between CHIP and complications. METHODS: The primary aim of this study was to determine the major complications in PCI. We included 989 PCI lesions and divided those into definite CHIP (n=140), possible CHIP (n=397), and the non-CHIP groups (n=452). RESULTS: The incidence of major complications was noted to be the highest in the definite CHIP, followed by the possible CHIP, and lowest in the non-CHIP (p=0.001). The multivariate logistic regression analysis using a generalized estimating equation revealed definite CHIP (versus non-CHIP: odds ratio (OR) 2.099, 95% confidence interval (CI) 1.062-4.150, p=0.033) was significantly associated with major complications after controlling for confounding factors. Another multivariate logistic regression analysis revealed immunosuppressive drugs (OR 3.040, 95% CI 1.251-7.386, p=0.014), unstable hemodynamics (OR 5.753, 95% CI 1.217-27.201, p=0.027), and frailty (OR 2.039, 95% CI 1.108-3.751, p=0.022) were significantly associated with major complications among CHIP factors. CONCLUSIONS: The incidence of major complications in complex PCI was determined to be the highest in the definite CHIP, followed by the possible CHIP and lowest in the non-CHIP. Thus, more attention should be given to the three components of CHIP to prevent major complications in complex PCI.

BACKGROUND AND AIMS: Intravascular ultrasound (IVUS) often allows us to observe reverberations behind calcification in percutaneous coronary intervention (PCI) to heavily calcified lesions. However, clinical significance of reverberations remains unknown. The aim of this study was to assess the impact of reverberations on stent expansion and clinical outcomes after PCI with rotational atherectomy (RA) to heavily calcified lesions. METHODS: We considered 250 calcified lesions that underwent IVUS-guided PCI with RA. According to the number of reverberations (NR), those lesions were divided into the high NR (≥3) group (n = 36) and the low NR (≤2) group (n = 214). Stent expansion and the cumulative incidence of ischemia-driven target lesion revascularization (ID-TLR) were compared between the high and low NR groups. RESULTS: The high NR group showed significantly smaller stent expansion rate than the low NR group (67.7% vs. 75.9%, respectively, p=0.02). The multivariate logistic regression analysis showed that high NR and calcified nodule were significantly associated with stent underexpansion. The incidence of ID-TLR was significantly higher in the high NR group than in the low NR group (p=0.03). In multivariate Cox hazard analysis, high NR and acute coronary syndrome were significantly associated with ID-TLR. CONCLUSIONS: High NR was significantly associated with stent underexpansion and ID-TLR. When high NR was detected by IVUS, the PCI strategy was be planned carefully to avoid stent underexpansion. The follow-up program of the patients with high NR might need to be scheduled prudently because of the high risk of TLR.

Some patients admitted to intensive care units (ICU) would develop delirium, which is associated with poor prognosis. The purpose of this retrospective study was to identify factors associated with ICU delirium in patients with acute myocardial infarction (AMI). We included 753 AMI and divided those into the ICU-delirium group (n = 110) and the non-ICU-delirium group (n = 643) according to the presence of ICU delirium. The ICU delirium was evaluated by confusion assessment method for the intensive care unit. Patient characteristics and clinical outcomes were compared between the 2 groups, and factors associated with ICU delirium were sought by multivariate analysis. The prevalence of female sex was significantly higher in the ICU-delirium group (43.6%) than in the non-ICU-delirium group (20.2%) (p < 0.001). The incidence of in-hospital death was significantly higher in the ICU-delirium group (17.3%) than in the non-ICU-delirium group (0.5%) (p < 0.001). The multivariate logistic regression analysis revealed that age [every 10 years increase: odds ratio (OR) 1.439, 95% confidence interval (CI) 1.127-1.837, p = 0.004], female sex (OR 2.237, 95%CI 1.300-3.849, p = 0.004), triple vessel disease (OR 2.317, 95%CI 1.365-3.932, p = 0.002), body mass index < 18.5 kg/m2 (OR 2.910, 95%CI 1.410-6.008, p = 0.004), use of mechanical support (OR 2.812, 95%CI 1.500-5.270, p = 0.001), respiratory failure (OR 5.342, 95%CI 3.080-9.265, p < 0.001), and use of continuous renal replacement therapy (OR 5.901, 95%CI 2.520-13.819, p < 0.001) were significantly associated with ICU delirium. In conclusion, ICU delirium was associated with in-hospital death. Older age, female sex, triple vessel disease, leanness, use of mechanical support, respiratory failure, and continuous renal replacement therapy were significantly associated with the occurrence of ICU delirium.

OBJECTIVES: This study aimed to investigate the relationship between immediate incomplete stent apposition (ISA) detected by intravascular ultrasound (IVUS) and midterm stent failure. BACKGROUND: Stent failure is one of serious clinical events related to percutaneous coronary intervention (PCI). The previous studies using optical coherence tomography showed that ISA could be associated with stent thrombosis. However, the association between immediate ISA detected by IVUS and stent failure has not been fully investigated. METHODS: We included 396 lesions that underwent elective PCI, and divided those into the appropriate stent apposition (ASA) group (n = 290) and the ISA group (n = 106). The primary endpoint was stent failure, which was defined as a composite of ischemia-driven target lesion revascularization and stent thrombosis. We compared clinical and lesion characteristics between the two groups, and performed a multivariate COX hazard analysis to investigate the association between immediate ISA and stent failure. RESULTS: The median follow-up duration was 1296 days. The Kaplan-Meier curves revealed the higher incidence of stent failure in the ISA group than in the ASA group (p < 0.001). The multivariate stepwise COX hazard analysis showed that immediate ISA (hazard ratio 4.97, 95% confidence interval 1.31-18.82, p = 0.018) was significantly associated with stent failure. When we set the cut-off value of the immediate ISA distance as 0.25 mm, the distance ≥ 0.25 mm had 68.8% sensitivity and 85.0% specificity to predict stent failure. CONCLUSIONS: Immediate ISA detected by IVUS was associated with midterm stent failure. We should pay attention to reduce immediate ISA for improving the midterm outcomes.

AIMS: Coronary calcification detected by coronary angiography is a simple risk marker for long-term clinical outcomes in stable coronary artery disease. However, the significance of angiographic coronary calcification in the culprit lesion of acute myocardial infarction (AMI) has not been fully discussed. The purpose of this retrospective study was to assess the usefulness of angiographic coronary calcification as a risk marker for long-term clinical outcomes following percutaneous coronary intervention to the culprit lesions of AMI. METHODS: We included 1209 patients with AMI and divided them into the none-mild calcification group (n=923) and the moderate-severe calcification group (n=286) according to angiographic coronary calcification in the culprit lesion of AMI. The primary endpoint was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, nonfatal MI, readmission for heart failure, and ischemia-driven target vessel revascularization. RESULTS: The median follow-up duration was 542 (Q1: 182, Q3: 990) days. A total of 345 MACE were observed during the study period. The occurrence of MACE was significantly greater in the moderate-severe calcification group than in the none-mild calcification group (43.4% vs. 23.9%, p＜0.001). In the multivariate Cox hazard model, moderate-severe calcification was significantly associated with MACE (hazard ratio 1.302, 95% confidence interval 1.011-1.677, p=0.041) after controlling multiple confounding factors. CONCLUSIONS: Angiographically moderate to severe calcification in AMI culprit lesion was associated with long-term worse clinical outcomes. Angiographic coronary calcification can be a simple risk marker in patients after AMI.