Association between major adverse cardiovascular events and pentraxin-3 in patients who have undergone coronary computed tomography angiography: from the FU-CCTA registry.

Chronic vasculitis is considered to be associated with future cardiovascular events. Here, we present major cardiovascular events (MACEs) in patients who underwent coronary computed tomography angiography (CCTA) for screening for coronary artery disease (CAD), and the association between MACEs and the inflammation marker pentraxin (PTX)-3 or highly sensitive C-reactive protein (hsCRP). The patients who underwent CCTA for the purpose of screening for CAD at Fukuoka University Hospital (FU-CCTA registry), 456 patients with suspected CAD or at least one cardiovascular risk factor were followed for up to 5 years. The levels of PTX-3 and hsCRP in blood were measured at the time of CCTA, and the patients were divided into two groups according to the presence (MACEs group) or absence (non-MACEs group) of MACEs. There were no differences in PTX-3 or hsCRP between the MACEs (-) and MACEs ( +) groups in all patients. A multivariate analysis related to the presence or absence of MACEs by logistic regression analysis of inflammation factors (PTX-3 and hsCRP) in addition to conventional risk factors as independent variables was performed. PTX-3 was a predictor of MACEs in males, whereas smoking, but not PTX-3, was a predictor of MACEs in females. PTX-3 could be a predictor of MACEs in males, but not females.

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.

A Rare Case of Submassive Pulmonary Embolism with a Right Aberrant Subclavian Artery and Thrombosed Kommerell Diverticulum.

An 81-year-old man presented with shortness of breath and was referred to our hospital with suspected acute pulmonary embolism. Enhanced computed tomography revealed a right aberrant subclavian artery with a thrombosed Kommerell diverticulum (KD), as well as deep vein thrombosis in the left leg and bilateral pulmonary artery thrombosis. Thrombosis in the KD disappeared after one month of anticoagulation treatment with rivaroxaban. Thrombosis of a KD is a rare condition that may cause distal emboli and subclavian steal syndrome, although this syndrome was not present in this case. Rivaroxaban is an effective anticoagulant for treating thrombosis of a KD.

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.

Postural Conversion Computed Tomography for the Diagnosis of Pneumopericardium due to Perforation by the Active Atrial Lead.

A 71-year-old woman with cardiac sarcoidosis underwent an implantable cardioverter-defibrillator implantation in the left precordium to prevent fatal arrhythmias. Two weeks later, she presented with dyspnea. Chest X-ray revealed right pneumothorax due to the active atrial lead perforation. Subsequently, air was detected surrounding the heart. Although it was difficult to differentiate pneumopericardium from pneumomediastinum, postural conversion computed tomography (CT) in the supine and prone positions documented air migration in the pericardial cavity and diagnosed pneumopericardium. This rare case of pneumopericardium combined with pneumothorax contralateral to the venous access site highlights the utility of postural conversion CT for diagnosis of pneumopericardium.

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.

Effects of Tolvaptan With or Without the Pre-Administration of Renin-Angiotensin System Blockers in Hospitalized Patients With Acute Decompensated Heart Failure.

We examined whether tolvaptan combined with an angiotensin II receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACE-I) is more effective than tolvaptan alone in the treatment of patients with heart failure (HF). Sixty-five hospitalized patients with acute decompensated HF were included in this study. They were divided into 2 groups; an ARB/ACE-I group (n = 44, who received ARB or ACE-I before the use of tolvaptan) and a non-ARB/ACE-I group (n = 21). There were no significant differences in patient characteristics including medications at baseline between the non-ARB/ACE-I and ARB/ACE-I groups with the exception of the percentages of hypertension and ischemic heart disease. Urinary volume (UV) at baseline in the ARB/ACE-I group was slightly higher than that in the non-ARB/ACE-I group. The increase in UV after the use of tolvaptan in the non-ARB/ACE-I group was significantly higher than that in the ARB/ACE-I group. The cardiothoracic ratio and the reduction in body weight were similar between the groups after tolvaptan use. Finally, in a logistic regression analysis, a response to the use of tolvaptan was independently associated with the non-use of ARB/ACE-I, but not with age, gender, body mass index, loop diuretic, or human arterial natriuretic peptide. In conclusion, tolvaptan alone might induce an increase in UV in decompensated HF patients without ARB/ ACE-I, although the treatment of HF with ARB/ACE-I is the first choice strategy.

The Change in Body Weight During Hospitalization Predicts Mortality in Patients With Acute Decompensated Heart Failure.

BACKGROUND: In our experience, the change in body weight (BW) during hospitalization varies greatly in patients with acute decompensated heart failure (HF). Since the clinical significance of a change in BW is not clear, we investigated whether a change in BW could predict mortality. METHODS: We retrospectively enrolled 130 patients (72 males; aged 68 ± 10 years) who were hospitalized due to acute decompensated HF and followed for 2 years after discharge. The change in the BW index during hospitalization (ΔBWI) was calculated as (BW at hospital admission minus BW at hospital discharge)/body surface area at hospital discharge. RESULTS: The patients were divided into quartiles according to ΔBWI, and the 2-year mortality rates in the quartiles with the lowest, second, third and highest ΔBWI were 18.8%, 12.1%, 3.1% and 9.1%, respectively. In a multivariate Cox proportional hazards analysis after adjusting for variables with a P value less than 0.05, ΔBWI was independently associated with 2-year mortality (P = 0.0002), and the quartile with the lowest ΔBWI had a higher relative risk (RR) for 2-year mortality than the quartile with the highest ΔBWI (RR: 7.46, 95% confidence interval: 1.03 - 53.99, P = 0.04). CONCLUSION: In conclusion, ΔBWI was significantly associated with 2-year mortality after discharge, which indicates that ΔBWI might be a simple predictor of prognosis in acute decompensated HF.

Efficacy and Safety of Combination Therapy Consisting of Angiotensin II Type 1 Receptor Blocker, Calcium Channel Blocker and Hydrochlorothiazide in Patients With Hypertension.

BACKGROUND: Many patients continue to have high blood pressure (BP) even after treatment with high-dose (H)-angiotensin II type 1 receptor blocker (ARB)/calcium channel blocker (CCB) or middle-dose (M)-ARB/CCB/hydrochlorothiazide (HCTZ). METHODS: Thirty-two hypertensive patients who had the use of H-ARB/CCB or M-ARB/CCB/HCTZ were enrolled in this study. We applied a changeover with a switch to H-ARB (telmisartan 80 mg/day)/CCB (amlodipine 5 mg/day or nifedipine CR 40 mg/day)/HCTZ (12.5 mg/day). RESULTS: Systolic BP (SBP) and diastolic BP (DBP) were significantly decreased in all patients and in the H-ARB/CCB and M-ARB/CCB/HCTZ groups after 3 months. Percentage (%) of patients who reached the target BP after 3 months (72%) in all patients was significantly higher than that at 0 months (19%). There were no serious adverse effects in any of the patients. CONCLUSIONS: Combination therapy with H-ARB/CCB/HCTZ was associated with a significant reduction of BP.

A rare case of eosinophilic granulomatosis with polyangiitis complicated with progressive pericardial effusion.

A 44-year-old woman had a 15-year history of asthma and had recently been treated for sinusitis and unidentified limb eruption. She had presented at a nearby clinic with inspiratory chest pain one week before hospitalization, and was diagnosed as having eosinophilic pneumonia based on peripheral blood eosinophilia and ground glass opacities in the right lung field, without pericardial effusion, as detected by chest computed tomography. She additionally presented with a feeling of chest tightness, and extensive pericardial effusion appeared within a week. She developed heart failure on admission, and we performed pericardiocentesis. We gave a clinical diagnosis of acute probable myopericarditis as the cause of pericardial effusion based on pleuritic chest pain, pericardial effusion, and elevation of cardiac enzymes, as well as eosinophilic granulomatosis with polyangiitis (EGPA) based on eosinophilia, her history of sinusitis, asthma, and migratory pulmonary opacities. We initiated oral prednisone 25 mg daily and pericardial effusion disappeared. In patients with EGPA, cardiac involvement is more serious than the involvement of other organs, and is associated with a poor prognosis. In this report we describe a rare case of EGPA complicated with progressive pericardial effusion and discuss the importance of the early diagnosis and treatment of EGPA. .

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.

Frequent Premature Ventricular Complexes Originating from the Left Ventricular Summit Successfully Ablated from the Proximal Great Cardiac Vein Using an Impedance-based Electroanatomical Mapping System.

We herein report a 58-year-old woman with frequent premature ventricular complexes (PVCs) originating from the left ventricular summit. The earliest ventricular activation of spontaneous PVCs was recorded in the proximal site of the great cardiac vein, which was simultaneously mapped and conducted using an impedance-based electroanatomical mapping system. Irrigated radiofrequency with a starting power output of 20 W and maximal temperature set at 40°C was applied with 10 Ω impedance fall, resulting in total disappearance of the frequent PVCs. The patient has remained free from PVCs for 18 months without requiring antiarrhythmic drug therapy.

Acute Myocardial Infarction in a 26-Year-Old Patient With Familial Hypercholesteremia.

A 26-year-old male suffered sustained chest pain. Electrocardiogram showed ST-segment elevation in the anteroseptal wall and reciprocal ST-segment change in the inferior wall. The troponin-I level and the white blood cell count were elevated. We gave a diagnosis of acute myocardial infarction. He underwent urgent coronary angiography, which revealed 90% diffuse stenosis in the middle right coronary artery and total occlusion in the proximal left anterior descending coronary artery (LAD). Since the electrocardiogram indicated that the culprit lesion was in the proximal LAD, we performed percutaneous coronary intervention. The coronary flow in the LAD was classified as thrombolysis in myocardial infarction trial 3. His coronary risk factors were obesity, smoking, family history, hypertension and diabetes, in addition to heterozygous familial hypercholesteremia (FH). Herein, we describe the case of a young patient with acute anteroseptal myocardial infarction and discuss the potential importance of controlling cholesterol levels in FH.

Circadian variations in laboratory measurements of coagulation assays after administration of rivaroxaban or warfarin in patients with nonvalvular atrial fibrillation.

BACKGROUND: Although rivaroxaban has a relatively shorter half-life and peak and trough plasma concentrations throughout the day than warfarin, rivaroxaban has been found to be non-inferior to warfarin in preventing thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We measured circadian variations in laboratory measurements of coagulation assays for chronic treatment with rivaroxaban or warfarin in patients with NVAF. METHODS: We included 28 consecutive patients with NVAF who were treated with rivaroxaban (n=13) or warfarin (n=15). Blood samples were collected at 6 AM, 11 AM, and 3 PM on the same day and on the next morning at 6 AM. Prothrombin time (PT), international normalized ratio of the PT (PT-INR), activated partial thromboplastin time (APTT), prothrombin fragment 1+2 (F1+2), and protein C level/activity were measured in each patient. RESULTS: PT and PT-INR were significantly and consistently lower, and the F1+2 and protein C level/activity were significantly and consistently higher throughout the day in rivaroxaban-treated patients than in warfarin-treated patients. Significant increases in PT and PT-INR were observed 3h after oral administration in the patients taking rivaroxaban in the morning, whereas, significant increases in the protein C level/activity were observed 3h after oral administration in the patients taking warfarin in the morning. CONCLUSIONS: The protein C level/activity was significantly and consistently higher in the rivaroxaban-treated patients than in the warfarin-treated patients throughout the day, which was in contrast to the findings for other coagulation assays. These findings may partly explain the specific persistent anticoagulant effects of rivaroxaban even during the trough phase of the plasma concentration.

Paradoxical nocturnal elevation of sympathetic tone and spontaneous ventricular fibrillation in Brugada syndrome.

BACKGROUND: Nocturnal dominance of the incidence of spontaneous ventricular tachyarrhythmias has been reported in patients with Brugada syndrome (BrS). The purpose of the present study is to analyze the QT dynamics and autonomic balance as well as their diurnal variations in BrS patients. METHODS: Of the 33 consecutive patients with BrS included in the study, 14 had a history of cardiopulmonary arrest due to spontaneous ventricular fibrillation (VF) episodes (VF-BrS) and 19 had asymptomatic BrS (A-BrS). QT dynamics and heart rate variability were analyzed using 24-h Holter electrocardiogram recordings. RESULTS: Of the total 14 first cardiopulmonary arrest episodes due to spontaneous VF, 11 (79%) occurred in VF-BrS patients during the nighttime or at rest. The QT/RR slope during daytime was significantly steeper than that during nighttime in the A-BrS patients (p=0.031), but not in the VF-BrS patients (p=1.0). There were significant diurnal differences pertaining to the high-frequency (HF) and low-frequency (LF)/HF ratios in the A-BrS patients (p=0.019 and p=0.019, respectively), but not in the VF-BrS patients (p=1.0 and p=1.0, respectively). The VF-BrS patients were characterized by relatively high LF/HF ratios, whereas the A-BrS patients were characterized by relatively low LF/HF ratios throughout the daytime and nighttime. Furthermore, the LF/HF ratios during the nighttime in the VF-BrS patients were significantly higher than those in the A-BrS patients (p=0.021). CONCLUSIONS: Most first episodes of spontaneous VF in the VF-BrS patients occurred during the nighttime or at rest. The autonomic imbalance of paradoxical nocturnal elevation of the sympathetic tone along with an underlying persistent sympathetic tone throughout the day may play a key role for spontaneous VF initiation in BrS patients.

Recent Patient Characteristics and Medications at Admission and Discharge in Hospitalized Patients With Heart Failure.

BACKGROUND: To improve the clinical outcome of heart failure (HF), it is important to evaluate the etiology and comorbidities of HF. We previously reported the baseline clinical characteristics and medications in hospitalized patients with HF in years 2000 - 2002 (group 2000) and 2007 - 2009 (group 2008). METHODS: We conducted a retrospective study of 158 patients who were hospitalized due to HF between 2012 and 2014 (group 2013) in the Department of Cardiology, Fukuoka University Hospital. We analyzed the clinical characteristics and medications at admission and discharge, and compared the findings in group 2013 to those in group 2000 and group 2008. RESULTS: The major causes of HF were ischemic heart disease, hypertensive cardiomyopathy, valvular heart disease, and dilated cardiomyopathy. The New York Heart Association classification in group 2013 was significantly higher than those in group 2000 and group 2008. There was no difference in the level of brain natriuretic peptide at admission between group 2008 and group 2013. Tolvaptan began to be administered in group 2013. The median dose of furosemide just before the use of tolvaptan was 40 mg/day. At discharge, group 2013 showed higher rates of ß-blocker and aldosterone antagonist. There was no difference in the frequency of loop diuretics. The dose of carvedilol at discharge was only 6.2 ± 4.0 mg/day. Antiarrhythmic drugs and ß-blocker were used more frequently in HF with reduced ejection fraction (EF) than in HF with preserved EF. CONCLUSIONS: We may be able to improve the clinical outcome of HF by examining the differences in the clinical characteristics and medications at admission and discharge in hospitalized patients with HF.

Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

OBJECTIVE: We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). METHODS: Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. RESULTS: The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. CONCLUSION: Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients.

Comparison of the efficacies of irbesartan and olmesartan after successful coronary stent implantation.

OBJECTIVE: We compared the efficacies of irbesartan and olmesartan after successful stent implantation in patients with stable angina. METHODS: Twenty-six patients were randomly divided into irbesartan and olmesartan groups and treated for approximately eight months (at follow-up coronary angiography). RESULTS: There were no differences in blood pressure (BP) reduction or late loss between the groups. The BP levels in both groups at follow-up were significantly reduced. The equality of variance of systolic (S)BP (i.e., the intragroup standard deviation of SBP) in the irbesartan group was significantly smaller than that observed in the olmesartan group at follow-up. In addition, log[pentraxin-3] was significantly decreased in all of the patients at follow-up, with no differences between the groups. Interestingly, the levels of log[high-sensitive C-reactive protein (hs-CRP)] measured at 0 weeks were positively associated with in-stent late loss, and among independent biochemical variables in addition to age, gender, body mass index and the kind of angiotensin receptor blockers at 0 weeks, only these levels were related to in-stent late loss, as assessed by a multivariate analysis. CONCLUSION: The ability of irbesartan to reduce BP is comparable to that of olmesartan, and irbesartan exhibits a lower variance of systolic BP after treatment. The level of log[hs-CRP] before stent implantation is a predictor of in-stent late loss.

Comparison of the efficacy and safety of irbesartan and olmesartan in patients with hypertension (EARTH study).

Fifty-four patients were randomly divided into irbesartan and olmesartan groups. Blood pressure (BP) was significantly decreased in all patients at 12 weeks. In particular, BP in patients who initially received irbesartan showed significant reductions. The equality of variance of BP in the irbesartan group was significantly smaller than that in the olmesartan group at 12 weeks. Blood concentrations of adiponectin were significantly increased in the irbesartan group at 12 weeks. Log [pentraxin-3] in the irbesartan group were significantly decreased. In conclusion, the ability of irbesartan to reduce BP is comparable to that of olmesartan with equivalent safety.