A Continuous Murmur as the Only Clinical Sign for Complex Coronary Artery Fistulas Diagnosis.

An asymptomatic patient presented at our hospital exhibiting a Brugada electrocardiography pattern with coronary artery fistulas. Coronary artery fistula is a congenital or acquired rare abnormal condition with increased symptoms and complications over time. In the absence of the therapeutic consensus, we discuss the association and management for this condition. (Level of Difficulty: Advanced.).

Association Between the Level of Low-Density Lipoprotein Cholesterol and Coronary Atherosclerosis in Patients Who Have Undergone Coronary Computed Tomography Angiography.

BACKGROUND: Although the Japan Atherosclerosis Society Guidelines 2017 recommend lower levels of low-density lipoprotein cholesterol (LDL-C, < 70 mg/dL or ≤ 100 mg/dL) to prevent secondary cardiovascular events, we cannot conclude that a low level of LDL-C prevents primary cardiovascular events in patients with suspected coronary artery disease (CAD). METHODS: We registered 1,016 patients who were clinically suspected to have CAD and who underwent coronary computed tomography angiography (CCTA) for screening of coronary atherosclerosis. We excluded 350 patients who were receiving anti-lipidemic therapies and finally analyzed 666 patients. The patients were divided into three groups according to the LDL-C level: < 70 mg/dL (n = 25, Low LDL-C), 70 - 99 mg/dL (n = 141, Middle LDL-C), and ≥ 100 mg/dL (n = 500, High LDL-C). A ≥ 50% coronary stenosis was initially diagnosed as CAD, and the number of significantly stenosed coronary vessels (VD), Gensini score and coronary artery calcification (CAC) score were quantified. RESULTS: There were no significant differences in age, high-density lipoprotein cholesterol, rates of hypertension, hemoglobin A1c, blood sugar or systolic blood pressure among the Low, Middle and High LDL-C groups. On the other hand, there were significant differences in rates of males, smoking, dyslipidemia and diabetes, diastolic blood pressure and triglyceride among the groups. The prevalence of CAD values in the Low, Middle and High LDL-C groups were similar, at 52%, 47%, and 46%, respectively. In addition, there were no significant differences in the number of VD, Gensini score or CAC score among the Low LDL-C, Middle LDL-C and High LDL-C groups. CONCLUSIONS: We showed that the level of LDL-C was not associated with the presence or severity of CAD, which indicates that we need to screen by CCTA to prevent primary coronary events even if patients without anti-lipidemic therapies show low levels of LDL-C.

Presence and severity of coronary artery disease in patients who achieved intensive blood pressure reduction at the time of coronary computed tomography angiography.

Blood pressure (BP)-lowering treatment should be aimed at achieving intensive BP control. Coronary computed tomography angiography (CCTA) has become more widely available and enables the accurate noninvasive assessment of coronary artery stenosis for screening. The presence and severity of coronary artery disease (CAD) in patients who achieved intensive BP control at the time of CCTA were compared to those in patients without hypertension (HTN). Nine hundred eighty-five consecutive subjects who were clinically suspected of having CAD or who had at least one cardiac risk factor underwent CCTA. The patients were divided into four groups: patients without HTN (non-HTN group), hypertensive patients who underwent intensive BP lowering (intensive group, <130/80 mmHg), patients who underwent standard BP lowering (standard group, 130-139/80-89 mmHg) and patients with uncontrolled BP (uncontrolled group, >140/90 mmHg). Interestingly, %CAD in the Intensive group was significantly higher than that in patients without HTN. The Intensive group was older and had a higher body mass index, more significantly stenosed coronary vessels, lower levels of high-density lipoprotein cholesterol in the blood, and higher rates of dyslipidemia, diabetes, and anti-dyslipidemia and anti-diabetic medication use than the non-HTN group. The presence of CAD in the Intensive group was independently associated with age, male and smoking, whereas the presence of CAD in the non-HTN group was associated with age, male and family history. Finally, predictors of the number of VDs in the non-HTN and intensive BP-lowering groups were age, male, DL, and intensive BP lowering. In conclusion, these results suggest that hypertensive patients need more rigorous management of other coronary risk factors, despite receiving intensive BP-lowering treatment.

Associations between smoking habits and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography as screening for coronary artery disease.

We analyzed whether smoking was associated with major adverse cardiovascular events (MACE) and the progression of coronary atherosclerosis as assessed by coronary computed tomography angiography (CCTA) as screening for coronary artery disease (CAD). We enrolled 443 patients who had all undergone CCTA and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. We divided the patients into smoking (past and current smoker) and non-smoking groups and into males and females, and evaluated the presence of CAD, severity of coronary atherosclerosis and MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization) with a follow-up of up to 5 years. %CAD and the severity of coronary atherosclerosis in the smoking group were significantly higher than those in the non-smoking group. %MACE in males and smokers were significantly higher than those in females and non-smokers, respectively. Interestingly, Kaplan-Meier curves also showed that female non-smokers enjoyed significantly greater freedom from MACE than female smokers (p = 0.007), whereas there was no significant difference in freedom from MACE between male non-smokers and male smokers (p = 0.984). Although there were no significant predictors of MACE in all patients according to a multiple logistic regression analysis, smoking was useful for predicting MACE in females, but not males. In conclusion, smoking was significantly associated with MACE in females, but not males, who underwent CCTA as screening for CAD.

Associations Between High Levels of High-Density Lipoprotein Cholesterol and the Presence and Severity of Coronary Artery Disease in Patients Who Have Undergone Coronary Computed Tomography Angiography.

BACKGROUND: Although a recent study in a Japanese cohort indicated that extremely high-density lipoprotein cholesterol (HDL-C, ≥ 90 mg/dL) had an adverse effect on atherosclerotic cardiovascular disease mortality, we could not conclude that high levels of HDL-C were associated with the presence or severity of coronary artery disease (CAD). METHODS: We enrolled 1,016 patients who were clinically suspected to have CAD and who underwent coronary computed tomography angiography (CCTA). The number of significantly stenosed coronary vessels (vessel disease (VD), ≥ 50% coronary stenosis is diagnosed as CAD) and the Gensini score were quantified using CCTA, and the lipid profile was measured. The patients were divided into four groups according to the HDL-C level: < 40 mg/dL (n = 115, low), 40 - 59 mg/dL (n = 530, normal), 60 - 89 mg/dL (n = 335, high) and ≥ 90 mg/dL (n = 36, very-high). RESULTS: The percentage (%) of CAD in the low, normal, high and very-high groups was 69%, 55%, 42% and 25%, respectively (P for trend < 0.01). The Gensini score in the low, normal, high and very-high groups was 20 ± 25, 12 ± 16, 8 ± 12 and 4 ± 6, respectively (P for trend < 0.01). The very-high group showed the lowest triglyceride (TG) levels among the four groups. There were no significant differences in the level of low-density lipoprotein cholesterol or % use of statin among the four groups. Finally, the presence of CAD was independently associated with a low level of HDL-C, in addition to age, male, high systolic blood pressure and hemoglobin A1c, but not TG, by a multivariate logistic regression analysis. CONCLUSIONS: High levels of HDL-C at the time of CCTA for screening were associated with a reduced presence and severity of CAD.

Sacubitril/Valsartan Inhibits Cardiomyocyte Hypertrophy in Angiotensin II-Induced Hypertensive Mice Independent of a Blood Pressure-Lowering Effect.

BACKGROUND: Hypertensive left ventricular hypertrophy is associated with the risk of heart failure, coronary heart disease and cerebrovascular disease. Although sacubitril/valsartan (SAC/VAL), a first-in-class angiotensin receptor neprilysin inhibitor, reduces the risks of death and hospitalization for patients with heart failure, its mechanism of action is not fully understood. We hypothesized that SAC/VAL is superior to other conventional drugs in reducing cardiac hypertrophy. METHODS: Male C57BL/6J mice were implanted with an osmotic pump containing angiotensin II (Ang II). After 7 days of Ang II infusion, mice were also treated with either SAC/VAL, valsartan, enalapril or vehicle alone each day for 2 weeks. Blood pressure measurement was done weekly, and echocardiography was performed before and 3 weeks after infusion of Ang II. Histological analyses were done using extracted heart to investigate cardiac hypertrophy and fibrosis. RESULTS: Ang II markedly elevated blood pressures in all of the treatment groups, and there were no differences in the degree of blood pressure reduction among the SAC/VAL-, valsartan- and enalapril-treated groups. Echocardiography showed that SAC/VAL significantly suppressed the increase in left ventricular (LV) wall thickness and tended to decrease LV mass. In a histological analysis, SAC/VAL inhibited Ang II-induced cardiomyocyte hypertrophy, and individual cardiomyocytes in the SAC/VAL group were smaller than those in the valsartan and enalapril groups. Although previous studies using animal models of heart failure have indicated that SAC/VAL attenuates cardiac fibrosis, we found no supporting evidence in this setting. CONCLUSIONS: SAC/VAL, valsartan and enalapril all attenuated cardiomyocyte hypertrophy in a mouse model of Ang II-induced cardiac hypertrophy. Of note, SAC/VAL most strongly suppressed hypertrophy in spite of similar blood pressure-lowering effects as valsartan and enalapril. The present study suggests that SAC/VAL may have a beneficial effect on the early stage of hypertensive heart disease.

A Coronary Artery Calcium Score of Zero in Patients Who Have Undergone Coronary Computed Tomography Angiography Is Associated With Freedom From Major Adverse Cardiovascular Events.

BACKGROUND: The coronary artery calcification score (CACS) is a good marker of future cardiovascular risk. We determined the association between the CACS and the prognosis in patients who have undergone coronary computed tomography angiography (CCTA). METHODS: We performed a prospective cohort study and enrolled 502 consecutive patients who underwent CCTA for screening of coronary artery disease (CAD) at Fukuoka University Hospital (FU-CCTA Registry) and either were clinically suspected of having CAD or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The patients were divided into CACS = 0 and CACS > 0 groups. Using CCTA, ≥ 50% coronary stenosis was diagnosed as CAD, and the number of significantly stenosed coronary vessels (VD), Gensini score and CACS were quantified. The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). RESULTS: %CAD, the number of VD and the Gensini score in the CACS = 0 group were significantly lower than those in the CACS > 0 group. %MACE in the CACS = 0 group was also significantly lower than that in the CACS > 0 group. Kaplan-Meier curves indicated that the CACS = 0 group showed significantly greater freedom from MACE than the CACS > 0 group (P = 0.008). Finally, only CACS = 0 was independently associated with MACE (odd ratio: 0.41, 95% confidence interval: 0.17 - 0.97, P = 0.041). CONCLUSIONS: A CACS of 0 in patients who underwent CCTA was associated with a good prognosis.

Associations between the psoas major muscle index and the presence and severity of coronary artery disease.

The associations between the presence and severity of coronary artery disease (CAD) and measurements of the psoas major muscle (PMM) as assessed by multidetector row coronary computed tomography angiography (MDCT) are not known.We enrolled 793 patients who were clinically suspected to have CAD or had at least one cardiac risk factor and had undergone MDCT. The number of significantly stenosed coronary vessels (VD) and measurements of the PMM index (PMMI) were determined using MDCT.PMMI in the CAD group was significantly lower than that in the non-CAD group in males, but not females. In addition, the levels of PMMI tended to increase as the number of VD decreased in males. When male patients were divided into 2 groups according to median value of age, that is, relatively younger (53.4 ±â€Š9.2 years) and older (72.6 ±â€Š5.7 years) groups, the presence of CAD was independently associated with PMMI in the younger group by a multiple logistic regression analysis. The cut-off level of PMMI that gave the greatest sensitivity and specificity for the diagnosis of CAD in younger males was 8.3 cm/m (sensitivity 0.441, specificity 0.752).In conclusion, PMMI may be an imaging marker for evaluating the presence and/or severity of CAD in males, and particularly in the non-elderly.

Regression and Stabilization of Coronary Vulnerable Plaque by Evolocumab as Assessed by Multidetector Row Computed Tomography.

A 65-year-old man was followed for his coronary conditions using 320-multi detector row computed tomography (MDCT) for 30 months. He had soft plaque in the right coronary artery (RCA) [mean density of plaque was 22 hounsfield units (HU)]. His initial serum low-density lipoprotein cholesterol (LDL-C) was 72 mg/dL. After 30 months, his serum LDL-C was 26 mg/dL under 5.0 mg/day rosuvastatin and evolocumab 140 mg/2 weeks. MDCT showed a regression of the plaque in the RCA and the plaque density was 114 HU (intermediate plaque). In conclusion, intensive lipid-lowering therapy with evolocumab induced the regression and stabilization of coronary vulnerable plaque.

Gap-related Pulmonary Vein and Left Atrial Flutter Mimicking Cavotricuspid Isthmus-dependent Atrial Flutter.

We herein report a 79-year-old man with recurrent atrial flutter (AFL) following catheter ablation for pulmonary vein (PV) isolation and block line of the cavotricuspid isthmus. An electrophysiological study and three-dimensional mapping results revealed left atrium (LA)-PV macroreentrant flutter caused by a conduction gap, possibly correlated to prior application, which mimicked cavotricuspid isthmus-dependent AFL. This LA-PV flutter was terminated after applying radiofrequency to the gap at the antrum near the bottom left inferior PV in the posterior LA wall. During follow-up, the patient did not present with atrial tachyarrhythmias; antiarrhythmic drugs were therefore not administered.

Pregnancy May Affect the Attenuation of an ST Segment Elevation in the Right Precordial Leads: A Female Patient with Brugada Syndrome.

A 30-year-old woman was referred to our hospital to undergo an evaluation for suspected Brugada syndrome. She showed no symptoms, but had a strong family history of sudden cardiac death. During observation, Holter electrocardiography (ECG), which had been performed to investigate her symptoms of occasional dizziness, showed a sinus node dysfunction with an occasional long sinus pause. An implantable cardioverter defibrillator (ICD) was therefore put in place, and bradycardia pacing from the ICD relieved those symptoms during the subsequent 18-month follow-up. The patient completed two pregnancies during the follow-up period. No symptomatic changes occurred during the pregnancies, but ECG indicated that an ST segment elevation in the right precordial leads was attenuated during the second and third trimesters of both pregnancies.

Anti-atherosclerotic effects of an improved apolipoprotein A-I mimetic peptide.

BACKGROUND: Apolipoprotein (Apo)A-I is a major protein component of high-density lipoprotein (HDL) that causes cholesterol efflux from peripheral cells through ATP-binding cassette transporter A1 (ABCA1) and the generation of HDL. Furthermore, it has a possible protective function against atherosclerotic cardiovascular disease (ASCVD). We previously developed a novel ApoA-I mimetic peptide without phospholipids (Fukuoka University ApoA-I Mimetic Peptide, FAMP). According to our previous studies, FAMP had an anti-arteriosclerotic effect. Since the required dose and reaction time of conventional FAMP were relatively large and short, respectively, we newly developed an improved FAMP (i-FAMP). METHODS AND RESULTS: We synthesized four candidate i-FAMPs, i-FAMP-D1, -D2, -D3 and -D4, and examined which i-FAMP has greater cholesterol efflux capacity than FAMP in A172 human glioblastoma cells transiently transfected with human ABCA1 cDNA. Only i-FAMP-D1 showed significantly greater cholesterol efflux capacity than conventional FAMP. i-FAMP-D1 formed stronger α-helical conformations than FAMP as assessed by circular dichroism spectra. Thus, we selected i-FAMP-D1 for further experiments. i-FAMP-D1 had a greater atheroprotective effect than FAMP in ApoE knockout mice. In addition, i-FAMP-D1 activated cholesterol efflux from macrophage to HDL more strongly than FAMP and increased cholesterol excretion from liver to feces. CONCLUSION: These results suggest that i-FAMP-D1 has a stronger anti-atherosclerotic effect than conventional FAMP.

Changes in the function of angiotensin II type 1 receptor due to cholesterol depletion from cell membrane.

Blockers of G-protein coupled receptors (GPCRs), angiotensin II (Ang II) type 1 (AT1) receptor and ß1-adrenergic (Ad) receptor, have been shown to improve the prognosis of cardiovascular disease. Cholesterol molecules in the cell membrane are needed to stabilize GPCRs as well as the cell membrane itself. We determined whether the functions of AT1 and ß1-Ad receptors were changed by cholesterol depletion from cardiovascular cell membranes. Ang II-induced inositol phosphate production through AT1 receptor was suppressed by cholesterol depletion from cell membranes using rosuvastatin or methyl-ß-cyclodextrin (MßCD), whereas isoproterenol-induced cyclic AMP production through ß1-Ad receptor did not change after cholesterol depletion. In addition, the binding affinities of Ang II and AT1 receptor blocker after cholesterol depletion were significantly lower than those before depletion. Although AT1 receptor expression levels did not change after cholesterol depletion, the expression levels of AT1 receptor that could bind to Ang II significantly decreased after depletion. The changes in the structure of AT1 receptor due to depletion were confirmed by substituted-cysteine accessibility mapping. In conclusion, Ang II-induced activation of AT1 receptor is reduced without affecting the function of ß1-Ad receptor after cholesterol depletion from cardiovascular cell membranes.

Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese.

The ability of pro-protein convertase subtilisin/kexin type 9 (PCSK9) levels to predict the presence or severity of coronary artery disease (CAD) remains controversial. The purpose of this study was to investigate these associations. We enrolled 393 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and underwent multidetector-row computed tomography coronary angiography. The presence of CAD (≥50% coronary stenosis), the number of significantly stenosed coronary vessels, and plasma levels of PCSK9 by ELISA were analyzed. Plasma PCSK9 levels (log-transformed data) were significantly associated with the presence of CAD. Next, we divided the patients into two groups (non-statin and statin groups) according to statin treatment. PCSK9 levels in the non-statin group were significantly lower than those in the statin group. There were no significant differences in PCSK9 levels between the absence and presence of CAD in the statin group. However, in the non-statin group, PCSK9 levels in patients with CAD were significantly higher than those in patients without CAD. PCSK9 levels, in addition to age, gender, BMI, DM and HDL-C, were independently associated with the presence of CAD by a multivariable analysis. In conclusion, our results demonstrated that plasma PCSK9 levels may be a marker for evaluating the presence of CAD.

Correction to: Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese.

In the original publication of the article, Tables 1, 2 and 3 was published incorrectly. Unnecessary inequality symbols were added to all the numbers in the 'p value' of Tables 1, 2 and 3. The correct tables should be as follows.

Association Between the Presence or Severity of Coronary Artery Disease and Pericardial Fat, Paracardial Fat, Epicardial Fat, Visceral Fat, and Subcutaneous Fat as Assessed by Multi-Detector Row Computed Tomography.

The associations between the presence or severity of coronary artery disease (CAD) and measurements of various kinds of fat as assessed by multidetector row computed tomography (MDCT) are unclear. We enrolled 300 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and had undergone MDCT. The number of significantly stenosed coronary vessels (VD), and measurements of pericardial fat index, paracardial fat index, epicardial fat index, visceral fat index, and subcutaneous fat index were quantified using MDCT. Plasma levels of adiponectin, pentaxin-3, and high-sensitivity C-reactive protein factors were also measured. Pericardial fat index, paracardial fat index, and visceral fat index in a CAD group were significantly greater than those in a non-CAD group. In addition, the levels of these fat indices tended to increase as the number of VD increased and were positively correlated with the Gensini score. The area-under-the-curve for paracardial fat index was significantly greater than those for the other parameters of fat index measured by a receiver-operating characteristic curve analysis. The cut-off level of paracardial fat index that gave the greatest sensitivity and specificity for the diagnosis of CAD was 54.9 cm3/m2 (sensitivity 0.710, specificity 0.552). The presence of CAD was independently associated with paracardial fat index, in addition to age and diabetes mellitus, by a multiple logistic regression analysis. In conclusion, paracardial fat index may be a marker for evaluating the presence or severity of CAD.

Safety of Landiolol Hydrochloride as a Premedication for Producing an Appropriate Heart Rate for Multidetector-Row Computed Tomography Coronary Angiography.

BACKGROUND: We evaluated the safety of a bolus injection of landiolol hydrochloride, an ultrashort-acting ß1-selective antagonist, as a premedication prior to multidetector-row computed tomography coronary angiography (CTA). METHODS: The subjects consisted of 176 patients (M/F = 64:112, 67 ± 11 years) who had heart rate (HR) at rest ≥ 70 beats/min (bpm) and underwent CTA. Systolic/diastolic blood pressure (SBP/DBP) and HR were measured before and after the administration of landiolol. RESULTS: SBP/DBP and HR upon entry to the CT room were 136 ± 17/80 ± 11 mm Hg and 83 ± 10 bpm, respectively. HR was significantly reduced at the time of CTA scan (62 ± 7 bpm). Next, we divided the patients into three groups according to HR upon entry to the CT room: 70 - 79 bpm (n = 76), 80 - 89 bpm (n = 60) and ≥ 90 bpm (n = 40). HR at the time of CTA scan was significantly lower than that upon entry to the CT room in all three groups: 70 - 79 bpm (74 ± 3 bpm upon entry to the CT room to 61 ± 6 bpm at the time of CAT scan), 80 - 89 bpm (84 ± 3 to 63 ± 7 bpm) and ≥ 90 bpm (98 ± 6 to 65 ± 7 bpm). Although SBP/DBP was significantly decreased after the CTA scan (123 ± 18/72 ± 12 mm Hg), landiolol had no severe adverse events throughout CTA. CONCLUSION: In conclusion, a bolus injection of landiolol reduced HR by about 20 bpm without any severe adverse effects. Thus, a bolus injection of landiolol hydrochloride may be a suitable pretreatment for controlling HR in CTA.

Evaluation of the antithrombotic abilities of non-vitamin K antagonist oral anticoagulants using the Total Thrombus-formation Analysis System®.

The Total Thrombus-formation Analysis System (T-TAS®) is a novel automated microchip flow-chamber system for the quantitative evaluation of thrombus formation under blood flow conditions. T-TAS® uses two types of microchip to evaluate thrombus formation: the AR-chip quantifies white thrombus formation and the PL-chip quantifies platelet thrombus formation. We assessed the antithrombotic abilities of various non-vitamin K antagonist oral anticoagulants (NOACs) using T-TAS®. One hundred and three consecutive patients who were hospitalized with cardiovascular diseases were enrolled. We divided the patients into 2 groups; a control group that did not receive an anticoagulant (non-AC group) and an anticoagulant group (AC group). The AC group was further divided into warfarin, dabigatran, rivaroxaban and apixaban groups. We performed common coagulation tests and evaluated the area under the flow pressure curve (AR-AUC and PL-AUC) to quantify antithrombotic ability using T-TAS® at the trough. There were no significant differences in patient characteristics between the non-AC and AC groups. Only 55.1 % of patients in the AC group achieved the target blood pressure (BP) of less than 130/80 mmHg. Compared with the non-AC group, AR-AUC was significantly decreased in the AC, warfarin, dabigatran and apixaban groups. Only the rivaroxaban group did not show a significant decrease in AR-AUC. NOACs showed a significant decrease in PL-AUC compared with the non-AC group. In conclusion, T-TAS® was a useful tool for evaluating anticoagulation activity. NOACs was significantly effective as an antiplatelet agent. BP control should be a higher priority than the selection of an anticoagulant drug, especially NOACs.

Evaluation of the Antithrombotic Effects of Rivaroxaban and Apixaban Using the Total Thrombus-Formation Analysis System®: In Vitro and Ex Vivo Studies.

BACKGROUND: The usefulness of the Total Thrombus-Formation Analysis System® (T-TAS®) for monitoring the anticoagulant effects of non-vitamin K oral anticoagulants (NOACs) in clinical practice has been poorly addressed. METHODS: NOACs (rivaroxaban and apixaban) were added to whole blood from healthy subjects in an in vitro study, and their effects on thrombus formation were evaluated by the T-TAS®. We also evaluated antithrombotic effects using ex vivo samples of whole blood from patients given rivaroxaban or apixaban at the respective trough and peak drug concentrations. RESULTS: T-TAS® could determine anticoagulant effects in whole blood treated with rivaroxaban or apixaban in vitro. The increases in the anticoagulant effects of rivaroxaban and apixaban from the trough to peak concentrations in whole blood were successfully monitored by the T-TAS® using ex vivo samples. The antithrombotic effects of rivaroxaban and apixaban (in terms of factor Xa inhibition) at the peak were strongly linked to those at the trough. CONCLUSION: T-TAS® could be a clinically useful tool for monitoring the anticoagulant effects of factor Xa inhibitors, and may represent an accurate quantitative analysis.

Rivaroxaban, a factor Xa inhibitor, induces the secondary prevention of cardiovascular events after myocardial ischemia reperfusion injury in mice.

OBJECTIVES: Rivaroxaban has been shown to reduce overall death from cardiovascular causes in patients with recent acute coronary syndrome. Therefore, we evaluated the secondary prevention of cardiovascular events after myocardial ischemia reperfusion injury and its mechanisms in mice. METHODS: After myocardial reperfusion injury, C57BL/6J mice were randomized to receive either no treatment or treatment for 14days with low and high doses of rivaroxaban. After 7days, mice were administered tissue factor as a secondary event. RESULTS: Based on a Kaplan-Meier curve analysis, the high-dose rivaroxaban group showed a significantly higher % survival than the no-treatment group from day 7 (after the administration of tissue factor) to day 14 (at the end of the experimental period). Left ventricular (LV) ejection fraction in both the low- and high-dose rivaroxaban groups improved compared to that in the no-treatment group. Moreover, mRNA levels of interleukin-6 and collagens 1α2 and 3α1 in the LV in the high-dose group were significantly suppressed compared to those in the no-treatment group. CONCLUSIONS: Rivaroxaban improved the survival rate, probably by improving cardiac function through the reduction of inflammatory and fibrotic factors in the LV. This effect may be due to the pleiotropic effects of rivaroxaban beyond its main effect as an anti-coagulant.