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BACKGROUND Collagen disease is an important cause of aortic regurgitation (AR). Although aortic valve surgery is recommended for patients with AR and depressed left ventricular (LV) function, there have been few reports about risk factors for LV dysfunction in patients with AR concomitant with collagen disease. METHODS AND RESULTS We conducted this study at Kumamoto University Hospital in Japan. A total of 41 patients who had moderate to severe AR and concomitant collagen disease between January 2014 and December 2019 were enrolled. With regard to baseline characteristics, there were no significant differences in the type of collagen disease or El Khoury class between patients with preserved LV function and those with reduced LV function. B-type natriuretic peptide (375.2 [257.9-3852.6]pg/ml vs. 64.0 [33.3-133.6]pg/ml, p

Background The impact of intra-atrial conduction delay on the recurrence of atrial tachyarrhythmia after radio frequency catheter ablation (RFCA) has not been fully elucidated. Methods We retrospectively analyzed 155 AF patients who were sinus rhythm at the start of RFCA. The conduction time from the onset of the earliest atrial electrogram at the high right atrium (HRA) to the end of the latest electrogram at the coronary sinus (CS) during sinus rhythm was defined as HRA-CS conduction time. Pulmonary vein isolation (PVI) was performed followed by linear roof lesion and complex fractionated atrial electrogram (CFAE) ablation until AF termination. We evaluated atrial tachyarrhythmia recurrence 12 months after RFCA. Results The follow-up data were available for 148 patients. The recurrence of atrial tachyarrhythmia was noted in 28 (18.9%) patients. Atrial tachyarrhythmia recurrence patients had longer HRA-CS conduction times (151.3 ± 22.1 ms vs 160.1 ± 32.6 ms, p = .017). The patients were divided into the long or short HRA-CS conduction time group. The Kaplan–Meier analysis revealed that the long HRA-CS conduction time group held a higher risk of atrial tachyarrhythmia recurrence (log-rank test, p = .019). The multivariable Cox hazard analysis revealed that a long HRA-CS conduction time was a significant risk factor for the recurrence of atrial tachyarrhythmia, despite a long AF duration, persistent AF, and larger left atrial diameter (LAD) were not statistically significant. Conclusions The HRA-CS conduction time was the primary influencing factor that predicted the recurrence of atrial tachyarrhythmia after catheter ablation.

BACKGROUND Programmed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS. METHODS We prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded. RESULTS Totally, 446 CAD patients [ACS, n = 124; chronic coronary syndrome (CCS), n = 322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0-260.8) pg/mL, p

Background Antithrombotic therapy is established for the treatment of various cardiovascular events. However, it has been shown to increase the bleeding risk. Total Thrombus-formation Analysis System (T-TAS) is reported to be useful for evaluating thrombogenicity. Here, we estimated whether T-TAS is useful for predicting bleeding events risk in patients undergoing percutaneous coronary intervention (PCI). Methods This was a retrospective, observational study at Kumamoto University Hospital between April 2017 and March 2019. Blood samples obtained on the day of PCI were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip). We divided the study population into 2 groups according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) (182 patients in ARC-HBR positive, 118 in ARC-HBR negative). The primary endpoint was 1-year bleeding events that were defined by Bleeding Academic Research Consortium type2, 3, or 5. Results The AR10-AUC30levels were significantly lower in the ARC-HBR positive group than in the ARC-HBR negative group (median [interquartile range] 1571.4 [1277.0–1745.3] vs. 1726.2 [1567.7–1799.6], p Conclusions The results highlight that AR10-AUC30 evaluated by T-TAS could be a potentially useful marker for predicting high bleeding risk in patients undergoing PCI.

Background Malnutrition-Inflammation-Atherosclerosis (MIA) factors significantly and independently affect life prognosis of hemodialysis (HD) patients. We re-evaluated Japanese data, which have progressed ahead from a community-based observational study. The present study was designed to assess the contribution of these MIA factors to the mortality rate of Japanese HD patients in a community of 1.8 million people over a 36-month follow-up period. Methods and results A total of 5813 patients at 76 facilities were on maintenance HD in the Kumamoto Prefecture. Specifically, 4807 of these patients at 58 institutions were enrolled. Patients who exhibited lower serum albumin and higher serum C-reactive protein levels were defined as "malnourished" and "inflamed", respectively, compared with the median values. Patients who underwent invasive procedures for atherosclerotic diseases were defined as "atherosclerotic". The 36-month all-cause mortality rate in Japanese HD patients was 12.4%. This rate directly correlated with the number of MIA factors. The odds ratio of the all-cause mortality rate markedly and significantly increased as the number of factors increased. The presence of 3 MIA factors in HD patients was a significant predictor of mortality, as evidenced by a multivariate logistic regression analysis. Conclusions This study clearly demonstrated the close association between MIA syndrome and high mortality in Japanese HD patients. Early detection and the adjustment of MIA factors are mandatory.

Because diastolic late mitral annular velocity (a') obtained by transthoracic-echocardiography (TTE) represents left atrial (LA) function, we investigated the clinical significance of a' in heart failure (HF) with a preserved left ventricular (LV) ejection fraction (HFpEF).We enrolled 448 consecutive HFpEF patients (sinus rhythm: 66.3%, atrial fibrillation [AF] rhythm: 33.7%) and performed TTE under stable conditions after optimal therapy. In patients with sinus rhythm, a' values were measured at septal mitral annuli.A' had weak but significant negative correlations with the natural-logarithm-B-type natriuretic peptide (Ln-BNP), LA diameter, LV mass index and tricuspid regurgitation pressure gradient. Receiver operating characteristic (ROC) curve analysis showed that the best cut-off value of a' and systolic mitral annular velocity (s') for the prediction of HF-related events were 7.45 cm/s and 6.5 cm/s with areas under the curve (AUC) of 0.841 and 0.682, respectively. The AUC of ROC analysis for the logistic regression model of a' plus s' was improved to 0.97. In Kaplan-Meier analysis, HFpEF patients with low-a' (7.45 cm/s) had a significantly higher risk of total cardiovascular and HF-related events (both p .01 by log-rank test) than those with high-a' (≥ 7.45 cm/s) and were prognostically equivalent to those with AF. Multivariate Cox proportional hazard analysis identified low-a' as an independent predictor of both total cardiovascular (hazard ratio [HR]: 0.823, 95% confidence interval [CI]: 0.714-0.949, p = .007) and HF-related events (HR: 0.551, 95% CI: 0.422-0.720, p .001).A' value measurement is a non-invasive and useful method for risk stratification in HFpEF.

In patients undergoing dialysis therapy, mitral annular calcification (MAC) is a powerful predictor of cardiovascular events and all-cause mortality. However, there is little data on predictors for MAC progression in patients undergoing dialysis therapy.We retrospectively analyzed 98 hemodialysis-dependent patients in Japanese Red Cross Kumamoto Hospital who underwent routine transthoracic echocardiography (TTE) in 2017. Three patients with history of surgical valve replacement or severe valvular heart diseases were excluded. In the 95 enrolled patients, MAC was detected by TTE in 28 patients (29%). A multivariate logistic regression analysis revealed that duration of hemodialysis therapy was independently associated with presence of MAC (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.02-1.16; p 0.01). Among the 95 patients, 72 patients also underwent routine TTE 5 years previously in 2012. In these patients, progression of MAC from 2012 to 2017 was observed in 11 patients (15%). A multivariate logistic regression analysis revealed that number of coronary risk factors (OR: 2.67; 95% CI: 1.24-5.76; p = 0.01), baseline MAC diameter (OR: 1.23; 95% CI: 1.05-1.45; p = 0.01), and left atrial diameter (OR: 0.81; 95% CI: 0.68-0.95; p = 0.01) were significantly associated with progression of MAC.Accumulation of coronary risk factors was associated with progression of MAC in patients undergoing dialysis. Management of coronary risk factors may be important for inhibition of MAC progression.

Background Percutaneous coronary intervention (PCI) for unprotected left main truncus (LMT) lesions is controversial. Inoperable status with advanced age, renal dysfunction, frailty, or patient request may require an unprotected left main PCI. PCI for LMT is not recommended in the typical clinical situation; however, when it is the only feasible option, the performance is not bad. We demonstrated the result of a cobalt-chromium everolimus-eluting stent (CoCr-EES) in the LMT stenting and serial changes via micro-computed tomography (μCT). μCT is an established imaging technique used for high-resolution, non-destructive assessment of vascular samples. The technique has drawn increasing interest for investigations of atherosclerotic arteries in both humans and animal models. There are no reports regarding the linkage between clinical results and μCT images. Methods and results Between January 2009 and December 2014, we recruited 118 consecutive, unprotected LMT stenting cases in our institution. We examined the clinical outcomes and angiographic results with a CoCr-EES compared with a first-generation drug-eluting stent. The primary endpoint of this registry was the rate of one-year major adverse cardiac events (MACE). The one-year MACE rate was 2.54%; this did not include the CoCr-EES. We established LMT bifurcation models (mini-crush and culotte) using a CoCr-EES and obtained μCT images of the CoCr-EES. The images showed no deformation or strut apposition. Conclusion CoCr-EES performed well in LMT in our institution and according to μCT. μCT images may be useful for anatomical simulation in stent deployment.

Thrombus formation is one of the main pathogeneses of acute coronary syndrome with atherosclerotic rupture. Previous studies have reported that atherosclerosis increases platelet aggregability and that vascular endothelial dysfunction reflects early change of atherosclerosis. However, the relationship between coronary endothelial dysfunction and platelet reactivity remains unclear. Therefore, in this study, we investigated the relationship between them in non-obstructive ischemic heart disease (IHD) patients.Three hundred sixty-eight consecutive stable patients with suspected angina presenting non-obstructive coronary arteries (50% diameter) in coronary angiography were investigated with the intracoronary acetylcholine provocation test and measured adenosine triphosphate-induced coronary flow reserve. Finally, 25 non-obstructive IHD patients who had no anti-platelet agents were assessed for the relationship between coronary blood flow volume (CBFV) change and platelet aggregability as P2Y12 reaction unit (PRU) by VerifyNow P2Y12 assay system.CBFV change by intracoronary 20 μg/kg per minute acetylcholine provocation showed a significant negative correlation with platelet aggregability as PRU (r = 0.44, P = 0.03). Conversely, there was no significant correlation between PRU and endothelial function as coronary flow reserve. Furthermore, multivariable linear regression analysis indicated that an incremental CBFV change was independently associated with PRU (β = 0.63, P 0.001) in non-obstructive IHD patients.In patients with non-obstructive IHD, CBFV change was significantly associated with platelet aggregability, indicating that coronary endothelial dysfunction might mediate higher platelet aggregability.

"Onco-cardiology" is a term that indicates cardiotoxicity during treatment of malignant diseases. Many studies have demonstrated that chemotherapy agents induce cardiotoxicity in certain ratios. In clinical settings, active malignant diseases or a history thereof are often encountered in patients with cardiovascular disease (CVD); it is not uncommon for a patient to struggle with a prior treatment. We have previously demonstrated a close association between malignant diseases and coronary calcifications in coronary artery disease. The concurrence of arteriosclerotic diseases, including CVD, with malignant diseases should be carefully considered in clinical settings, particularly with regard to scheduled surgical procedures. Moreover, it is essential that all medical professionals associated with cancer care understand these associations. Our advocacy will provide new insight into onco-cardiology.

Sarcopenia is frequently observed and associated with poor outcomes in patients with chronic kidney disease (CKD). A simple screening test for sarcopenia using age, grip strength, and calf circumference was recently developed. However, the clinical utility of this sarcopenia score in patients with CKD remains unclear.We calculated the sarcopenia score of 265 patients with CKD and followed the patients for cardiovascular events. The endpoint of this study was the composite of cardiovascular hospitalization and total mortality. We divided all participants into high (n = 166) and low (n = 99) sarcopenia score groups using a simple scoring system. Patients in the high sarcopenia score group showed significantly higher plasma B-type natriuretic peptide (BNP) levels than those in the low sarcopenia score group (median: 103.1, interquartile range: 46.3-310.0 vs. 46.7, 18.0-91.8 pg/mL; p 0.0001). The Kaplan-Meier curve revealed that the risk of cardiovascular events was significantly greater in the high sarcopenia score group (log-rank test: p 0.0001), even after potential confounding factors were corrected using propensity score matching. Multivariate Cox hazard analysis identified a high sarcopenia score (hazard ratio: 3.04, 95% confidence interval: 1.45-6.38, p = 0.003) as an independent predictor of the primary endpoints. Furthermore, the combination of a high sarcopenia score and high BNP level identified patients with a significantly higher probability of future events (p 0.0001).This study demonstrates that this simple screening score for sarcopenia could be a useful tool for estimating the future adverse event risk in patients with CKD.

Background The most common reason for premature discontinuation of dual anti-platelet therapy (DAPT) after coronary stenting is the manifestation of gastrointestinal bleeding. Before percutaneous coronary interventions (PCIs), we screened patients who tested positive for fecal occult blood (fecOB). Methods and results On 1789 consecutively admitted cardiac catheterization patients, we performed fecOB examinations; 647 of these patients received PCIs, and 232 of them were fecOB positive. Ultimately, we performed 165 colonoscopies and detected 3 early cancer lesions. Conclusions Positive results on fecOB screening, before PCI, could indicate lower intestinal lesions. We can perform surgical cancer procedures safely, even with aspirin usage.

High incidence of coronary spasm after percutaneous coronary interventions Comparison between new generation drug-eluting stent and bare-metal stent Seiji Hokimoto ⁎, Yuji Mizuno , Daisuke Sueta , Sumio Morita , Tomonori Akasaka , Noriaki Tabata , Eisaku Harada , Yuichiro Arima , Megumi Yamamuro , Tomoko Tanaka , Eiichiro Yamamoto , Kenji Sakamoto , Kenichi Tsujita , Koichi Kaikita , Hirofumi Yasue , Hisao Ogawa a

Malnutrition-Inflammation-Atherosclerosis (MIA) factors significantly and independently affect life prognosis of hemodialysis (HD) patients. We re-evaluated Japanese data, which have progressed ahead from a community-based observational study. The present study was designed to assess the contribution of these MIA factors to the mortality rate of Japanese HD patients in a community of 1.8 million people over a 36-month follow-up period.A total of 5813 patients at 76 facilities were on maintenance HD in the Kumamoto Prefecture. Specifically, 4807 of these patients at 58 institutions were enrolled. Patients who exhibited lower serum albumin and higher serum C-reactive protein levels were defined as "malnourished" and "inflamed", respectively, compared with the median values. Patients who underwent invasive procedures for atherosclerotic diseases were defined as "atherosclerotic". The 36-month all-cause mortality rate in Japanese HD patients was 12.4%. This rate directly correlated with the number of MIA factors. The odds ratio of the all-cause mortality rate markedly and significantly increased as the number of factors increased. The presence of 3 MIA factors in HD patients was a significant predictor of mortality, as evidenced by a multivariate logistic regression analysis.This study clearly demonstrated the close association between MIA syndrome and high mortality in Japanese HD patients. Early detection and the adjustment of MIA factors are mandatory.

The aim was to examine the prevalence and characteristics of epicardial vasomotor abnormality (EVA) and coronary microvascular dysfunction (CMD) including endothelium-dependent (EDCMD) or -independent (EICMD) in patients following a second-generation drug-eluting stent (second DES) implantation without in-stent restenosis.In 105 patients who underwent second DES implantation in the left anterior descending coronary artery (74 men; mean age, 67.9±9.6years), and in 105 suspected angina patients without stenting (65 men; mean age 66.4±9.1years), we evaluated EVA using the acetylcholine provocation test, EDCMD and EICMD by measuring the coronary flow reserve and the relationship between myocardial ischemia (intracoronary lactate production between aorta and coronary sinus and ST-T changes) or recurrent angina and vascular function. There was no difference in the incidence of EVA between DES and control (49.5% versus 55.2%; P=0.41). Given that the prevalence of CMD was higher in DES than in control (59.0% versus 29.5%; P0.001), CMD may be associated with stent placement. Of the CMD patients, EDCMD alone, EICMD alone, and both CMDs were found in 40.3%, 22.6%, and 37.1%, respectively. Myocardial ischemia was detected in 42.4% of patients, and recurrent angina was more common in the presence of both EDCMD and EICMD in patients with EVA or CMD compared to patients with normal vascular function (EVA, 42.9% versus 7.7%, P=0.015: CMD, 39.1% versus 7.7%, P=0.007).Myocardial ischemia and recurrent angina may be caused by the presence of both EDCMD and EICMD after a second DES implantation without ISR.

The term "onco-cardiology" has been used in reference to cardiotoxicity in the treatment of malignant disease. In actual clinical situations, however, cardiovascular disease (CVD) associated with malignant disease and the concurrence of atherosclerotic disease with malignant disease are commonly observed, complicating the course of treatment. Patients with malignant disease associated with coronary artery disease often die from the cardiovascular disease, so it is essential to classify these disease states. Additionally, the prevalence of these classifications makes it easy to manage patients with malignant disease and coronary artery disease. We divided the broad field of onco-cardiology into 4 classifications based on clinical scenarios (CSs): CS1 represents the so-called paraneoplastic syndrome. CS2 represents cardiotoxicity during treatment of malignant diseases. CS3 represents the concurrence of atherosclerotic disease with malignant disease, and CS4 represents cardiovascular disease with benign tumors. This classification facilitates the management of patients with malignant disease and coronary artery disease by promoting not only the primary but also the secondary prevention of CVD.

Coronary spasm is one of the mechanisms of myocardial infarction with nonobstructive coronary arteries (MINOCA). The aim of this study was to investigate the effects of aspirin on future cardiovascular events in patients with coronary vasospastic angina (VSA) with non-significant atherosclerotic stenosis.This was the retrospective analysis of the 640 VSA patients with non-significant atherosclerotic stenosis (≤50% stenosis) among 1,877 consecutive patients who underwent acetylcholine (ACh)-provocation testing between January 1991 and December 2010. The patients were divided into 2 groups treated with (n=137) or without (n=503) low-dose aspirin (81-100mg/day). We evaluated major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction, and unstable angina.In the study population, 24 patients (3.8%) experienced MACE; there were 6 cases in VSA patients with aspirin and 6 in those without aspirin. Multivariate Cox hazards analysis for correlated factors of MACE indicated that use of statin (HR: 0.11; 95% CI: 0.02 to 0.84; P=0.033), ST-segment elevation during attack (HR: 5.28; 95% CI: 2.19-12.7; P0.001), but not the use of aspirin as a significant predictor of MACE. After propensity score matching (n=112, each), Kaplan-Meier survival analysis indicated almost identical rate of 5-year survival free from MACE in those with aspirin, compared to those without aspirin in the entire and matched cohort (P=0.640 and P=0.541, respectively).Low-dose aspirin might not reduce future cardiovascular events in VSA patients with non-significant stenosis.

Although acute coronary syndrome (ACS) mainly arises from plaque ruptures (PR), precise mechanisms underlying ACS without PR are unknown. We sought to examine clinical, angiographic and intravascular ultrasound (IVUS) characteristics of ACS without PR.Culprit lesions of 161 ACS patients were categorized by the presence or absence of PR (PR group: n=57, Non-PR group: n=104). Lower abdominal circumference (86±10cm vs 90±9cm, p=0.02), lower prevalence of myocardial infarction (53% vs 82%, p=0.0002), and higher prevalence of definite vasospasm (15% vs 2%, p=0.006) were found in Non-PR group. Morphologically, Non-PR group was associated with simpler Ambrose classification (36% vs 14%, p=0.004), less hypoechoic plaque (45% vs 65%, p=0.04) and lower incidence of IVUS-detected thrombus (21% vs 54%, p0.0001), compared with PR group. On quantitative IVUS, although minimum lumen area (MLA) was similar between the groups, vessel (14.2±5.4mm(2) vs 17.5±5.1mm(2), p=0.0002) and plaque (11.6±5.0mm(2) vs 14.9±4.9mm(2), p0.0001) areas were significantly smaller at MLA site in Non-PR group than in PR group. On multivariate analysis, average plaque area was only an independent IVUS-predictor of non-rupture ACS (odds ratio: 0.85, p=0.01).Compared to ACS with PR, non-rupture ACS arise from more hyperechoic (allegedly "stable") plaque with smaller vessel and plaque area, leading to lower incidence of thrombotic occlusion. Coronary vasospasm might be a possible pathogenic mechanism underlying non-rupture ACS.