Serum microRNA-126 and -223 as new-generation biomarkers for sarcoidosis in patients with heart failure.

BACKGROUND: Although cardiac sarcoidosis is associated with poor prognosis, diagnosis of the disease is challenging and the sensitivity and specificity of diagnostic modalities are limited. This study was performed to evaluate the potential of serum microRNAs (miRNAs) as diagnostic biomarkers for cardiac sarcoidosis. METHODS: We performed genome-wide expression profiling for 2565 miRNAs (Human-miRNA ver.21) using peripheral blood samples from 5 patients with cardiac sarcoidosis (61±9 years) and 3 healthy controls (54±7 years). From this screening study, we selected 12 miRNAs that were significantly related to cardiac sarcoidosis. Next, we performed real-time polymerase chain reaction (PCR) on blood samples from 15 new patients with cardiac sarcoidosis and 4 healthy controls to quantify the expression of these 12 miRNAs. RESULTS: In the screening study, 12 miRNAs were differentially expressed (p<0.01) in all 5 patients with cardiac sarcoidosis, showing greater fold-change values (>4 or <0.25) compared with the expression in the 3 healthy controls. Analysis of the real-time PCR for blood samples from the other 15 patients and 4 controls using Mann-Whitney U tests revealed that the expression of miR-126 and miR-223 was significantly higher in the patients than in the healthy individuals. However, there were no differences in the expressions of miRNA-126 and miR-223 between patients with only cardiac lesions and those with extra-cardiac lesions. CONCLUSIONS: Our results demonstrate the potential of serum miR-126 and miR-223 as new-generation biomarkers for the differential diagnosis of cardiac sarcoidosis in patients with heart failure.

Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension.

OBJECTIVES: The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. METHODS: The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group). RESULTS: Systolic blood pressure in the aged group declined significantly from 155 ± 18 mmHg at baseline to 138 ± 11 mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 ± 20 mmHg at baseline to 142 ± 13 mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. CONCLUSIONS: Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.

Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction.

Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

Prescription patterns of oral anticoagulants for patients with non-valvular atrial fibrillation: experience at a Japanese single institution.

New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (>65 years) than in those who received warfarin (P < 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.

Takotsubo cardiomyopathy with involvement of delayed-onset rhabdomyolysis and acute kidney injury after rosuvastatin treatment.

Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient's medical condition, in association with complaints of non-specific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient's cardiac function.

Role of the left atrial function on the pseudonormalization of the transmitral flow velocity pattern evaluated by two-dimensional tissue tracking technique.

BACKGROUND: Mechanisms of the pseudonormalization (PN) of the transmitral flow (TMF) velocity pattern have been mainly attributed to left ventricular diastolic function. PURPOSE: To assess the influence of left atrial (LA) function on the PN with two-dimensional tissue tracking technique. METHODS: The subjects consisted of 21 healthy volunteers and 70 patients with various cardiac diseases. Images of one cardiac cycle in the apical four-chamber view were stored by the HIVISION 900 (Hitachi Medico, Chiba, Japan). The LA volume (LAV) loop was created using two-dimensional tissue tracking technique and LAV index (LAVI) at a given cardiac phase was calculated. A preload of 90mmHg was applied using a customized lower body positive pressure (LBPP) system. Patients were divided into the PN group (n=18) with their early diastolic TMF velocity (E) increased and late diastolic TMF velocity (A) decreased, and the non-(N)-PN group (n=52) with both E and A wave velocities increased by LBPP. RESULTS: (1) During LBPP, the LAVImax in both the groups increased significantly. (2) In the N-PN group, the LAVIpass (p<0.001), LAVIact (p<0.01), and LAVItotal (p<0.0001) increased significantly. The dV/dts (p<0.0001) and dV/dtE (p<0.0001) increased significantly with an increase in the dV/dtA. On the other hand, there was no change in those parameters except LAVIpass (p<0.05) and dV/dtE (p<0.05) significantly increased in the PN group. (3) As a result, the LAVImin was significantly greater in the PN group than in the N-PN group (p<0.0001) during LBPP. The ratio of E velocity to early diastolic mitral annular velocity (E/E') during LBPP was significantly greater in the PN group than in the N-PN group (p<0.0001). CONCLUSIONS: The lack of an increase in active LA emptying volume in response to an increase of preload leads to elevated LA pressure and the pseudonormalization of the TMF velocity pattern in patients with various cardiac diseases.