Takayoshi Yamashita

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.

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

BACKGROUND AND AIMSnLenvatinib (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.nnnMETHODSnTen consecutive DTC patients who did not take any cardiovascular agents were orally administered 24xa0mg 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.nnnRESULTSnAll 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.nnnCONCLUSIONSnWe 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. 1450–1956u2009cm 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.

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 CHADS 2 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 CHADS 2 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 CHADS 2 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 CHADS 2 score categories. CHADS 2 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 CHADS 2 score (log‐rank test, P<0.001). Multivariate Cox hazard analysis identified CHADS 2 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 CHADS 2 score is useful for the prediction of cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation.