Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 µm vs 26 ± 24 µm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

Incidence, clinical course, and risk factors in the development of femoral pseudoaneurysm after atrial fibrillation ablation.

Background: Previous studies have revealed the risk factors for femoral pseudoaneurysms (FPA). Most data on FPA are based on coronary and peripheral interventions, with limited studies focusing on atrial fibrillation (AF) ablation. However, patient backgrounds, anticoagulation regimens, and vascular access methods differ. In addition, a standard for managing FPA after AF ablation remains elusive due to the difficult nature of achieving thrombosis in pseudoaneurysms. Methods: This single-center, retrospective, observational study included 2805 consecutive patients who underwent AF ablation between January 2016 and December 2021. All patients underwent femoral artery and vein punctures. Puncture sites were checked 1 day post-procedure. Results: A total of 23 FPA patients were identified during the study period. Multivariate logistic regression analysis showed that hypertension (odds ratio 4.66, 95% confidence interval: 1.38-15.71; p = .0032) and warfarin use (odds ratio 3.83, 95% confidence interval: 1.40-10.45; p = .021) were significantly associated with the occurrence of FPA. The compression success rate was low (22%). There were nine and six patients in the endovascular treatment (EVT) and ultrasound-guided thrombin injection (UGTI) groups, respectively. The success rates were 100% and 84% in the EVT and UGTI groups, respectively. The length of hospital stay after FPA treatment was 2.1 days in the EVT group and 1.3 days in the thrombin group. Conclusion: We must be careful about post-procedural FPA, especially for hypertension and warfarin-using patients. Treatment of pseudoaneurysms with anticoagulants is unlikely to achieve hemostasis, and an early switch to invasive treatments, such as EVT, should be considered.

Action Quality Assessment Model Using Specialists' Gaze Location and Kinematics Data-Focusing on Evaluating Figure Skating Jumps.

Action quality assessment (AQA) tasks in computer vision evaluate action quality in videos, and they can be applied to sports for performance evaluation. A typical example of AQA is predicting the final score from a video that captures an entire figure skating program. However, no previous studies have predicted individual jump scores, which are of great interest to competitors because of the high weight of competition. Despite the presence of unnecessary information in figure skating videos, human specialists can focus and reduce information when they evaluate jumps. In this study, we clarified the eye movements of figure skating judges and skaters while evaluating jumps and proposed a prediction model for jump performance that utilized specialists' gaze location to reduce information. Kinematic features obtained from the tracking system were input into the model in addition to videos to improve accuracy. The results showed that skaters focused more on the face, whereas judges focused on the lower extremities. These gaze locations were applied to the model, which demonstrated the highest accuracy when utilizing both specialists' gaze locations. The model outperformed human predictions and the baseline model (RMSE:0.775), suggesting a combination of human specialist knowledge and machine capabilities could yield higher accuracy.

A case of chronic total occlusion in popliteal artery recanalized by double snare piercing technique.

BACKGROUND: Although majority of cases with chronic total occlusion (CTO) in femoro-popliteal lesion were treated with antegrade approach only, some lesions require alternative approach due to its complexity. Bi-directional approach is useful on endovascular therapy (EVT) for CTO; however guidewire passage through the lesion is impossible in some challenging cases. The present case shows a successful re-entry technique utilizing two snare catheters from an antegrade and retrograde access site (double snare piecing technique). CASE PRESENTATION: A 79-year-old woman with right leg intermittent claudication (Rutherford category IV), who had undergone unsuccessful EVT for popliteal CTO, required another EVT for the worsening symptom. Following the failed conventional crossing technique (wire knuckle technique, intravascular-ultrasound-guided wiring, and controlled antegrade and retrograde subintimal tracking technique), two snare catheters were placed and the snare loops were pierced by a puncture needle percutaneously. After an 0.014 wire was inserted into the needle, the needle was withdrawn. The wire was pulled from the retrograde side and was externalized. Then, the antegrade snare catheter was pulled and externalized, to make the wire across the lesion. After that, a microcatheter was advanced along the externalized wire from the retrograde side and cross the lesion. The wire was replaced with a new wire, which completely created pull-through system. After the hemostasis by balloon inflation and lesion preparation, this procedure was completed with an endoluminal-covered stent and two inter-woven stents. The re-entry site was covered by the inter-woven stent. Her symptoms improved after the procedure, and the lesion has not developed restenosis at 2-years follow-up. CONCLUSIONS: This re-entry technique of puncturing two snare loops (double snare piercing technique) might be effective for achieving successful passage through challenging femoropopliteal CTO cases.

Impact of High Implantation of Transcatheter Aortic Valve on Subsequent Conduction Disturbances and Coronary Access.

BACKGROUND: Data regarding the impact of high transcatheter heart valve (THV) implantation on coronary access after transcatheter aortic valve replacement (TAVR) as assessed by postimplantation computed tomography (CT) are scarce. OBJECTIVES: The authors sought to assess the impact of high THV implantation on coronary access after TAVR. METHODS: We included 160 and 258 patients treated with Evolut R/PRO/PRO+ and SAPIEN 3 THVs, respectively. In the Evolut R/PRO/PRO+ group, the target implantation depth was 1 to 3 mm using the cusp overlap view with commissural alignment technique for the high implantation technique (HIT), whereas it was 3 to 5 mm using 3-cusp coplanar view for the conventional implantation technique (CIT). In the SAPIEN 3 group, the HIT employed the radiolucent line-guided implantation, whereas the central balloon marker-guided implantation was used for the CIT. Post-TAVR CT was performed to analyze coronary accessibility. RESULTS: HIT reduced the incidence of new conduction disturbances after TAVR for both THVs. In the Evolut R/PRO/PRO+ group, post-TAVR CT showed that the HIT group had a higher incidence of the interference of THV skirt (22.0% vs 9.1%; P = 0.03) and a lower incidence of the interference of THV commissural posts (26.0% vs 42.7%; P = 0.04) with access to 1 or both coronary ostia compared with the CIT group. These incidences were similar between the HIT and CIT groups in the SAPIEN 3 group (THV skirt: 0.9% vs 0.7%; P = 1.00; THV commissural tabs: 15.7% vs 15.3%; P = 0.93). In both THVs, CT-identified risk of sinus sequestration in TAVR-in-TAVR was significantly higher in the HIT group compared with the CIT group (Evolut R/PRO/PRO+ group: 64.0% vs 41.8%; P = 0.009; SAPIEN 3 group: 17.6% vs 5.3%; P = 0.002). CONCLUSIONS: High THV implantation substantially reduced conduction disturbances after TAVR. However, post-TAVR CT revealed that there is a risk for unfavorable future coronary access after TAVR and sinus sequestration in TAVR-in-TAVR. (Impact of High Implantation of Transcatheter Heart Valve during Transcatheter Aortic Valve Replacement on Future Coronary Access; UMIN000048336).

Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers.

Background: Alcohol-a risk factor for atrial fibrillation (AF)-is metabolized by aldehyde dehydrogenase 2 (ALDH2). Dysfunctional alleles of ALDH2 (ALDH2-deficient variants) are prevalent among East Asians. Objectives: Because the prevalence of AF is estimated to be high in ALDH2-deficient variant carriers, we investigated the correlation between AF and ALDH2-deficient variant carriers, including the association with habitual alcohol consumption. Methods: A total of 656 consecutive patients were included in this investigation. ALDH2 genotypes were divided into ALDH2 homozygous wild-type (∗1/∗1), ALDH2 heterozygous-deficient allele (∗1/∗2), and ALDH2 homozygous-deficient allele (∗2/∗2). Multivariate analyses were applied to determine the correlation between ALDH2 genotype and AF. Results: ALDH2∗1/∗2 and ALDH2∗2/∗2 carriers who were ALDH2-deficient variant carriers comprised 199 (30.3%) and 27 (4.1%) patients, respectively. Among these patients, the proportions of habitual alcohol consumption were 26.1% and 0%, respectively. Multivariate analysis revealed that ALDH2∗1/∗2 itself was not a risk factor for AF (odds ratio [OR]: 1.28; P = 0.21). However, habitual alcohol consumption in ALDH2∗1/∗2 carriers was an independent risk factor of AF (OR: 4.13; P = 0.001). Contrary to expectations, ALDH2∗2/∗2 itself had a lower incidence of AF among other risk factors (OR: 0.37; P = 0.03). Conclusions: Although the ALDH2∗1/∗2 itself was not associated with AF, ALDH2∗1/∗2 carriers with habitual alcohol consumption could experience AF because of slow alcohol metabolism. In contrast, ALDH2∗2/∗2 itself had a lower incidence of AF. This might be related to the absence to habitual alcohol consumption in ALDH2∗2/∗2 carriers because of the negligible activity of ALDH2. Thus, abstaining from alcohol consumption might prevent the development of AF in patients who are ALDH2∗1/∗2 carriers.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

Temporal trends in coronary intervention strategies and the impact on one-year clinical events: data from a Japanese multi-center real-world cohort study.

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used.

East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known. The study subjects comprised 218 Japanese patients with STEMI (158 men and 60 women, mean age 67.9 ± 11.9) who underwent successful percutaneous coronary intervention. Of these, 120 (55.0%) were the carriers of variant ALDH2*2 and 98 (45.0%) those of wild ALDH2*1/*1 on genotyping. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit (14.2% vs 46.3%, P < 0.001) in the ALDH2*2 group. The peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, however, were significantly higher in the patients with ALDH2*2 than in those with ALDH2*1/*1 [a median 275.0 (175.8-407.5) vs 177.5 (126.9-344.3) U/L, P = 0.001] among men but not among women (P = 0.811). There was a significant interaction between men (male sex) and ALDH2*2 for I/R injury (χ2 = 4.425, P = 0.040). The variant ALDH2*2 was associated with more severe I/R injury than the wild ALDH2*1/*1 in STEMI patients in men with possible sex differences.

Imaging-guided PCI for event suppression in Japanese acute coronary syndrome patients: community-based observational cohort registry.

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P < 0.001). Even after propensity-score matching, the event rates still showed significant differences between the two groups (log-rank P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR ( http://www.umin.ac.jp/ctr/ ). Identifier: KICS (UMIN000015397).

Impact of hydrostatic pressure on fractional flow reserve: in vivo experimental study of anatomical height difference of coronary arteries.

BACKGROUND: Although pressure equalization of the sensor-tipped guidewire and systemic pressure is mandatory in measuring fractional flow reserve (FFR), pressure in the distal artery (Pd) with wire advancement can be influenced by hydrostatic pressure related to the height difference between the catheter tip and the distal pressure sensor. We therefore analyzed the impact of hydrostatic pressure on FFR in vivo by modification of the height difference. METHODS: To reveal the anatomical height difference in human coronary arteries, measurement was performed during computed tomography angiography (CTA) of five consecutive patients. Utilizing the healthy coronary arteries of female swine, height difference diversity was reproduced by body rotation and vertical inclination. FFR measurements were performed during maximum hyperemia with adenosine. The height difference was calculated fluoroscopically with a contrast medium-filled balloon for reference. RESULTS: In human coronary CTA, height averages from the ostium in the left anterior descending artery (34.6 mm) were significantly higher than in the left circumflex (-15.5 mm, p = 0.008) and right coronary arteries (-2.3 mm, p = 0.008). In our swine model, reproduced height variation ranged from -7.2 cm to +6.5 cm. Mean FFR was significantly lower in positive sensor height and higher in negative sensor height compared to the reference height. Linear regression analyses revealed significant correlations between height difference and FFR, observed among all coronary arteries, as well as between the height difference and Pd-aortic pressure mismatch. Subtracting 0.622 mmHg/cm height difference from Pd could correct the expected hydrostatic pressure influence. CONCLUSION: Hydrostatic pressure variation resulting from sensor height influenced FFR values might affect interpretation during FFR assessment.

A case of repetitive acute coronary syndrome in a patient with familial hypercholesterolemia.

The low-density lipoprotein-cholesterol (LDL-C) level of a 60-year-old woman diagnosed with acute coronary syndrome (ACS) was 212 mg/dL. She was suspected of having familial hypercholesterolemia, therefore, administration of a proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody in addition to atorvastatin plus ezetimibe was initiated, reducing her LDL-C level to 42 mg/dL. Nine months after initial ACS, the PCSK9 antibody was discontinued. Six months after the iturruption, she relapsed with ACS, and neoatherosclerosis progression was confirmed via intravascular ultrasound. Then, the PCSK9 antibody was reintroduced. Disruption of a PCSK9 may be associated with the progression and destabilization of neoatherosclerosis. .

Reduction in thrombogenic activity and thrombocytopenia after transcatheter aortic valve implantation - The ATTRACTIVE-TTAS study.

INTRODUCTION: Bleeding complications after transcatheter aortic valve implantation (TAVI) is a major problem in clinical practice. However, there is few information on thrombogenicity after TAVI. The aim of this study was to establish a monitoring of total thrombogenicity in perioperative TAVI using the Total Thrombus-formation Analysis System (T-TAS), a microchip-based flow chamber system for analysis of thrombus formation under flow condition. METHODS: Twenty-three patients with severe aortic stenosis who underwent TAVI between August 2017 and March 2018 at Kumamoto university hospital were enrolled. After exclusion, data of 21 patients were analyzed. Blood samples were obtained before, 2, 7, and 30 days after TAVI. Thrombogenicity were assessed by the T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip. We also measured platelet count, high-molecular-weight von Willebrand factor (HMW-vWF) multimers, and plasma thrombopoietin. Computational fluid dynamics (CFD) analysis was performed to calculate the wall shear stress (WSS). RESULTS: The AR10-AUC30 levels and platelet counts were significantly lower at 2 days post-TAVI, and then increased gradually. HMW-vWF multimers, and plasma thrombopoietin, were significantly higher at 2 days post-TAVI, compared with before TAVI. CFD analysis showed that WSS of the aortic valve and posterior ascending aortic wall were significantly lower after TAVI than before-TAVI. Multivariate analysis identified max velocity measured by echocardiography, platelet count, and D-dimer as significant determinants of AR10-AUC30, representing total thrombogenicity. CONCLUSIONS: Although HMW-vWF multimers improved earlier after TAVI, total thrombogenic activity evaluated by T-TAS remained relatively low followed by improvement in thrombogenic activity at 30 days after TAVI.Clinical Trial Registration: https://clinicaltrials.gov. Unique identifiers: NCT03248232.

Prognostic Value of the CHADS2 Score for Adverse Cardiovascular Events in Coronary Artery Disease Patients Without Atrial Fibrillation-A Multi-Center Observational Cohort Study.

BACKGROUND: The CHADS2 score has mainly been used to predict the likelihood of cerebrovascular accidents in patients with atrial fibrillation. However, increasing attention is being paid to this scoring system for risk stratification of patients with coronary artery disease. We investigated the value of the CHADS2 score in predicting cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation. METHODS AND RESULTS: This was a multicenter, observational cohort study. The subjects had been admitted to one of the participating institutions with coronary artery disease requiring percutaneous coronary intervention. We calculated the CHADS2 scores for 7082 patients (mean age, 69.7 years; males, 71.9%) without clinical evidence of atrial fibrillation. Subjects were subdivided into low- (0-1), intermediate- (2-3), and high-score (4-6) groups and followed for 1 year. The end point was a composite of cardiovascular/cerebrovascular death, nonfatal myocardial infarction, and ischemic stroke at 1-year follow-up. Rates of triple-vessel/left main trunk disease correlated positively with CHADS2 score categories. CHADS2 scores among single, double, and triple-vessel/left main trunk groups were 2 (1-2), 2 (1-3), and 2 (2-3), respectively (P<0.001). A total of 194 patients (2.8%) had a cardiovascular/cerebrovascular event, and Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular/cerebrovascular events in proportion to a higher CHADS2 score (log-rank test, P<0.001). Multivariate Cox hazard analysis identified CHADS2 score (per 1 point) as an independent predictor of cardiovascular/cerebrovascular events (hazard ratio, 1.31; 95% CI, 1.17-1.47; P<0.001). CONCLUSIONS: This large cohort study indicated that the CHADS2 score is useful for the prediction of cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation.

Lenvatinib, an oral multi-kinases inhibitor, -associated hypertension: Potential role of vascular endothelial dysfunction.

BACKGROUND AND AIMS: Lenvatinib (Lenvima®), an oral multi-kinase inhibitor, is effective in the treatment of differentiated thyroid carcinomas (DTCs). A severe adverse effect of lenvatinib is hypertension, thus limiting its use as an anti-cancer treatment. Although the pathogenesis of hypertension is generally assumed to involve microvascular bed reduction and an increase in peripheral vascular resistance due to a decrease in nitrogen oxide (NOx) production after vascular endothelial growth factor (VEGF) inhibition, the effects of hypertension on vascular endothelial function in actual patients remain unclear. Here, we examined how lenvatinib affects vascular endothelial function. METHODS: Ten consecutive DTC patients who did not take any cardiovascular agents were orally administered 24 mg of lenvatinib once daily. Using an EndoPAT2000® system, we used reactive hyperemia-peripheral arterial tonometry (RH-PAT) and evaluated vascular endothelial function on the basis of the RH-PAT index (RHI). We expressed the results as %RHI, which indicates the change compared with pretreatment levels. Additionally, we measured serum NOx and plasma VEGF concentrations pre- and post-treatment. RESULTS: All of the patients treated with lenvatinib exhibited significant hypertension; the %RHI levels were significantly decreased the day after treatment with lenvatinib. Furthermore, serum NOx and plasma VEGF concentrations were significantly decreased and increased, respectively, compared with pretreatment levels. These results indicate that hypertension induced by lenvatinib may be caused by a decrease in nitric oxide production, as a result of VEGF inhibition and impaired vascular endothelial function. CONCLUSIONS: We provide the first demonstration that lenvatinib causes hypertension via vascular endothelial dysfunction in human subjects.

Relationship between asymptomatic intra-cranial lesions and brachial-ankle pulse wave velocity in coronary artery disease patients without stroke.

Little is known about the significance of asymptomatic intra-cranial lesions (ICL) identified by brain MRI in coronary artery disease (CAD) patients. Silent cerebral lesions are suggested to be associated with arterial stiffness in healthy subjects. We investigated whether subclinical ICL are associated with arterial stiffness and the prognosis in CAD patients without medical history of cerebrovascular diseases. We recruited CAD patients who required percutaneous coronary intervention (PCI), did not meet exclusion criteria, and agreed with MRI before PCI. Subjects were divided into two groups according to the presence of ICL of cerebral microbleeds or lacunar infarction. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). Clinical outcome was defined as a composite of cardiovascular death, non-fatal myocardial infarction, stroke, unstable angina and heart failure. In total, 149 patients underwent brain MRI. Patients with ICL (n=55) had significantly higher baPWV than those without ICL (1591-2204 vs. 1450-1956 cm per sec; P=0.009). A multivariate analysis showed that male sex (odds ratio (OR), 3.15; 95% confidence interval (CI), 1.38-7.20; P=0.006) and baPWV (OR, 1.001; 95% CI, 1.000-1.002; P=0.023) were predictors of ICL. In total, 12 patients experienced a cardiovascular event. The Kaplan-Meier analysis indicated a significantly higher incidence of cardiovascular events in patients with ICL (log-rank test: P=0.018). Multivariate Cox proportional hazards analyses indicated that ICL finding was a significant predictor of clinical outcome (hazard ratio, 3.41; 95% CI, 1.02-11.5; P=0.047). Patients with subclinical ICL had a higher baPWV and worse prognoses than those without ICL.

The dawn of a new era in onco-cardiology: The Kumamoto Classification.

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.