Association between paroxysmal or persistent atrial fibrillation and hyperuricemia in patients who underwent coronary computed tomography angiography: from the FU-CCTA-AF Registry.

BACKGROUND: Hyperuricemia (HU) and hypertension (HTN) contribute to atherosclerotic cardiovascular disease, and both are also involved in the onset and development of atrial fibrillation (AF). OBJECTIVE: In the present study, we investigated the association between risk factors for atherosclerosis [including HU, HTN, blood pressure and serum uric acid (UA) levels] and paroxysmal atrial fibrillation (Paro-AF) or persistent atrial fibrillation (Pers-AF) in patients who underwent coronary computed tomography angiography (CCTA). METHODS: We enrolled 263 patients from the Fukuoka University-CCTA-AF (FU-CCTA-AF Registry) who underwent CCTA prior to AF ablation therapy. AF was classified as either Paro-AF (≤ 7 days) or Pers-AF (> 7 days). HU was diagnosed by a serum UA level > 7.0 mg/dl, and coronary artery disease (CAD) was diagnosed when CCTA results showed ≥ 50% significant coronary artery stenosis. The number of significantly diseased coronary artery vessels (VD), the Gensini score and the coronary artery calcification score (CACS) were measured. Left atrial morphology was also evaluated. RESULTS: Diastolic blood pressure and HbA1c in the Pers-AF group were significantly higher than those in the Paro-AF group. The Pers-AF group showed a significantly higher prevalence of HU and higher UA levels than the Paro-AF group. In a multivariate logistic regression analysis, HU was an independent associated factor to Pers-AF (odds ratio: 2.023, 95% confidence interval: 1.055-3.881, p = 0.034), while HTN was not. CONCLUSION: In patients with AF, HU is associated with Pers-AF.

Interference of cardiac implantable electronic devices and computed tomography imaging in the current era with a phantom model.

Introduction: Cardiac implantable electronic devices are used in patients with cardiac rhythm disorders. Computed tomography irradiation is not prohibited for patients with cardiac implantable electronic devices, despite adverse events being reported. Hence, appropriate preparation and knowledge are required before computed tomography irradiation can be carried out in these patients. Since there is limited knowledge or literature about the influence of computed tomography irradiation in cases with recent cardiac implantable electronic devices, we aimed to evaluate the adverse events and elucidate the necessary and sufficient safety measures associated with this therapy. Methods and Results: We placed cardiac implantable electronic devices on an anthropomorphic phantom model and observed their electrical activity in electrograms, while various protocols of computed tomography irradiation were implemented and adverse events evaluated. Oversensing with pauses of up to 3.2 s was observed in standard computed tomography protocols, but ventricular tachyarrhythmia or other clinically significant events could not be confirmed. Oversensing with pauses of up to 8.0 s was observed and ventricular tachyarrhythmia was detected in the maximum-dose protocols. However, treatments such as antitachycardia pacing or shock therapy for ventricular tachyarrhythmia were not observed because of their absence. Conclusion: Computed tomography irradiation for patients using cardiac implantable electronic devices is highly unlikely to cause clinically significant adverse events with the device settings and computed tomography protocols currently being used. Changing or monitoring the device settings routinely before computed tomography irradiation is not necessarily required for most patients.

Angiotensin Receptor Blocker and Neprilysin Inhibitor Suppresses Cardiac Dysfunction by Accelerating Myocardial Angiogenesis in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet.

MATERIALS AND METHODS: Male apolipoprotein E-knockout mice fed a high-fat diet were divided into control (CTL), valsartan (30 mg/kg) (VAL), sacubitril (30 mg/kg) (SAC), and valsartan plus sacubitril (30 mg/kg each) (VAL/SAC) groups after 4 weeks of prefeeding and were subsequently treated for 12 weeks. RESULTS: The VAL/SAC group exhibited significantly higher serum brain natriuretic peptide levels; more subtle changes in left ventricular systolic diameter, fractional shortening, and ejection fraction, and significantly higher expression levels of natriuretic peptide precursor B and markers of angiogenesis, including clusters of differentiation 34, vascular endothelial growth factor A, and monocyte chemotactic protein 1, than the CTL group. CONCLUSIONS: Valsartan plus sacubitril preserved left ventricular systolic function in apolipoprotein E-knockout mice fed a high-fat diet. This result suggests that myocardial angiogenic factors induced by ARNI might provide cardioprotective effects.

Combination of Linagliptin and Empagliflozin Preserves Cardiac Systolic Function in an Ischemia-Reperfusion Injury Mice With Diabetes Mellitus.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) and dipeptidyl peptidase 4 inhibitor (DPP4i) are oral hypoglycemic agents. Although SGLT2i has been shown having the beneficial effects on heart failure in basic and clinical studies, the combined effects of SGLT2i and DPP4i have not been established well. We investigated the effects of SGLT2i and DPP4i against diabetes mice model of myocardial ischemia-reperfusion injury. METHODS: Streptozotocin-induced diabetic C57BL/6J mice were divided into control (vehicle), empagliflozin (30 mg/kg/day), linagliptin (3 mg/kg/day) and combination (30 mg/kg/day and 3 mg/kg/day, respectively) groups. After 7 days of drug administration, 30 min of myocardial ischemia was performed. We investigated body weight, heart weight, blood glucose, and cardiac functions by pressure-volume Millar catheter followed by 28 days of additional drug administration. RESULTS: Blood glucose levels, body weight, and heart weight were not significantly different between the groups. In Millar catheter analysis, left ventricular volume at the peak left ventricular ejection rate which is one of the cardiac systolic parameters in combination group was significantly preserved than that in control (P = 0.036). The cardiac index in the combination group tended to be preserved compared to that in the control (P = 0.06). The pathological fibrotic area in the left ventricle in the combination group also tended to be smaller (P = 0.08). CONCLUSIONS: Combination therapy with linagliptin and empagliflozin preserved cardiac systolic function on the diabetes mice model of myocardial ischemia-reperfusion injury independent of blood glucose levels.

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.

Changes in serum levels of angiopoietin-like protein-8 and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 after ezetimibe therapy in patients with dyslipidemia.

Changes in serum levels of angiopoietin-like protein-8 (ANGPTL8) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) in patients with dyslipidemia after ezetimibe therapy remain to be elucidated. Thirty-eight patients who initially received ezetimibe and were followed for 16 weeks were enrolled. Various parameters were investigated before and after 16 weeks of ezetimibe treatment in all patients. In addition, the patients were also divided into metabolic syndrome (MetS) (n = 22) and Non-MetS (n = 16) groups, and various parameters were compared between these groups. ANGPTL8 was significantly positively correlated with triglyceride (TG) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) before treatment in all patients and in the MetS group. After treatment, TC and LDL-C were significantly decreased in all patients, and in both the MetS and Non-MetS groups, whereas there were no changes in TG or HDL-C. Serum levels of remnant-like particle cholesterol (RLP-C) significantly decreased in all patients and in the MetS group. The ANGPTL8 level before treatment was significantly positively associated with TG and negatively correlated with HDL-C in all patients and in the MetS group. ANGPTL8 and GPIHBP1were significantly decreased after treatment in all patients. GPIHBP1 was also significantly decreased after treatment in both groups. In conclusion, this is the first report to support the possibility of a new effect of ezetimibe therapy. Ezetimibe significantly decreased the serum level of LDL-C, but not TG or HDL-C, while reducing ANGPTL8 and GPIHBP1 in all patients with dyslipidemia. In addition, ezetimibe significantly decreased RLP-C levels in the MetS group.

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.