Rivaroxaban population pharmacokinetic and pharmacodynamic modeling in Iranian patients.

WHAT IS KNOWN AND OBJECTIVE: Although predictable pharmacokinetic and pharmacodynamic of rivaroxaban allow fixed dosing regimens without routine coagulation monitoring, there is still the necessity to monitor and predict the effects of rivaroxaban in specific conditions and different populations. The current study was designed and conducted to analyze the rivaroxaban population pharmacokinetics in Iranian patients and establish a pharmacokinetic/pharmacodynamic model to predict the relationship between rivaroxaban concentration and its anticoagulant activity. METHODS: A sequential nonlinear mixed effect pharmacokinetic/pharmacodynamic modeling method was used to establish the relation between rivaroxaban concentration and anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time (aPTT) as pharmacodynamic biomarkers in a population of sixty-nine Iranian patients under treatment with oral rivaroxaban. Rivaroxaban plasma concentration was quantified by a validated high-performance liquid chromatography-tandem mass spectrometry. RESULTS AND DISCUSSION: The typical population values (inter-individual variability%) of the oral volume of distribution and clearance for a one-compartment model were 61.2 L (21%) and 3.68 L·h-1 (61%), respectively. Creatinine clearance and Child-Turcotte-Pugh score were found to affect the clearance. A direct link linear structural model best fitted the data for both prothrombin time and aPTT. The baseline estimates of aPTT and prothrombin time in the population were 35.0 (15%) and 12.6 (2%) seconds, respectively. The slope of the relationship between apTT, prothrombin time, and rivaroxaban concentration was 0.033 (28%) and 0.018 (54%) s·ml·ng-1 , respectively. The selected model for anti-factor Xa activity consisted of a direct link inhibitory Emax model with Hill coefficient. The maximum level of inhibition (Emax ) was 4 IU·ml-1 . The concentration of rivaroxaban producing 50% of the maximum inhibitory effect (EC50 ) was 180 (24%) ng·ml-1 , and Hill coefficient (γ) was 1.44 (108%). No covariates showed a statistically significant effect on PT and activated partial thromboplastin time prolonging properties and anti-factor Xa activity. WHAT IS NEW AND CONCLUSION: Our results confirmed that pharmacokinetic/pharmacodynamic models similar to those of the other studies describe the relationship between the rivaroxaban concentration and its anticoagulant effect in Iranian patients. However, considerable differences were observed in the parameters of the pharmacodynamics-pharmacokinetic models with the results of other reports that can explain the unpredictable effects of rivaroxaban in some patients.

Heart rate variability changes by non-invasive ventilation in obesity hypoventilation syndrome.

BACKGROUND: Non-invasive positive pressure ventilation (NIPPV) is known to enhance hypoventilation and is particularly adopted as a treatment for patients diagnosed with obesity hypoventilation syndrome (OHS). The augmented risk of cardiovascular morbidity is known as a side effect of OHS. AIMS: In this paper, this inference is examined that hypoventilation and the increased risk of morbidity can be diagnosed via the assessment of changes in heart rate variability (HRV). More specifically, the study investigates the effect of NIPPV on both HRV and hypoventilation among OHS patients. The linear relationship between different HRV measures and ventilation parameters is also examined. MATERIALS & METHODS: The reported results are attained via an interventional clinical trial study. HRV measures are evaluated before and after treatment, in a group of patients which are newly diagnosed with OHS and receive bi-level positive airway pressure (BiPAP) treatment for three months. RESULTS: The results are compared and interpreted via statistical analysis. DISCUSSION: Throughout the study, the relationship between hypoventilation and HRV is confirmed, as well as the effect of BiPAP on some HRV measures in both time and frequency domains. Particularly significant connections are observed between hypoventilation and low-frequency components of HRV. CONCLUSION: The enhanced respiration due to the application of BiPAP can improve the performance of autonomous nervous and cardiovascular systems, in terms of HRV. Moreover, it is suggested to consider some HRV parameters to control the cardiovascular side-effects of OHS and confine the resulting mortality rate in long term.

Large Tricuspid Valve Myxoma in an Asymptomatic Patient with Uterine Myoma: An Uncommon Case.

Tricuspid valve myxomas are very uncommon tumors that could be found after the occurrence of pulmonary thromboembolism, symptomatic tricuspid obstruction, and right-sided heart failure. Herein, we describe a 42-year-old woman evaluated for an abdominal mass. In preoperative consultation, a tricuspid valve mass was detected in echocardiography. She underwent the removal of a benign uterine myoma and a myxoma of the tricuspid valve. Tricuspid valve myxomas constitute a scarce diagnosis. They could be asymptomatic, occurring in unusual locations and in association with benign tumors in other organs. Our patient was asymptomatic, underscoring the significance of the early diagnosis of this type of tumor to prevent further catastrophic events.

Alterations in the echocardiographic variables of the right ventricle in asymptomatic patients with breast cancer during anthracycline chemotherapy.

BACKGROUND: Anthracycline-induced cardiotoxicity can reach an irreversible phase; therefore great efforts are made to diagnose it early. As the right ventricle (RV) is smaller than the left, the right side of the heart is probably influenced by anthracycline to a greater extent and in a shorter time. The purpose of the present study was to investigate the early effects of chemotherapy on the right side of the heart. METHODS: This cross-sectional study was performed in Isfahan University hospitals from August 2014 to December 2015. Subjects were 67 patients with breast cancer who were planned to receive anthracycline for the first time. Echocardiography was performed before administration of anthracycline and 6 months later. Variables included right heart measures (RV end-diastolic dimensions, right atrium length and diameter), RV fractional area change (RVFAC), index of myocardial performance (Tei index), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure, lateral tricuspid annular early and late diastolic velocities, and tissue Doppler diastolic and systolic velocities. RESULTS: Forty-nine of the subjects completed the study. RV end-diastolic diameters and Tei index (0.31 to 0.37) were significantly increased (p<0.001). RVFAC (49.83% to 43.59%) and TAPSE (18.8 to 17.7 mm) were significantly decreased (p<0.001). There was a significant reduction in E (57.06 to 46.59 cm/s, p<0.001), E/A ratio (1.42 to 1.18, p<0.001), E' (16.73 to 12.4 cm/s, p<0.001), E'/A' ratio (1.21 to 0.9, p<0.001) and S' (12.59 to 10.57 cm/s, p<0.001). Systolic pulmonary arterial pressure (20.63 to 22.24 mm Hg, p=0.04) was significantly increased. CONCLUSIONS: This study shows a significant decrease in RV systolic and diastolic function during chemotherapy for 6 months. These reductions are in the normal range and can probably be considered an early indicator of anthracycline-induced cardiotoxicity.

Association between Latest Activated Sites in the Left Ventricle and Akinetic Segments in Patients with Ischemic Cardiomyopathy.

Background: It is not clear whether the latest activation sites in the left ventricle (LV) are matched with infracted regions in patients with ischemic cardiomyopathy (ICM). We aimed to investigate whether the latest activation sites in the LV are in agreement with the region of akinesia in patients with ICM. Methods: Data were analyzed in 106 patients (age = 60.5 ± 12.1 y, male = 88.7%) with ICM (ejection fraction ≤ 35%) who were refractory to pharmacological therapy and were referred to the echocardiography department for an evaluation of the feasibility of cardiac resynchronization therapy. Wall motion abnormalities, time to peak systolic myocardial velocity (Ts) of 6 basal and 6 mid-portion segments of the LV, and 4 frequently used dyssynchrony indices were measured using 2-dimensional echocardiography and tissue Doppler imaging (TDI). To evaluate the influence of the electrocardiographic pattern, we categorized the patients into 2 groups: patients with QRS ≤ 120 ms and those with QRS >120 ms. Results: A total of 1 272 segments were studied. The latest activation sites (with longest Ts) were most frequently located in the mid-anterior (n = 32, 30.2%) and basal-anterior segments (n = 29, 27.4%), while the most common sites of akinesia were the mid-anteroseptal (n = 65, 61.3%) and mid-septal (n = 51, 48.1%) segments. Generally, no significant concordance was found between the latest activated segments and akinesia either in all the patients or in the QRS groups. Detailed analysis within the segments indicated a good agreement between akinesia and delayed activation in the basal-lateral segment solely in the patients with QRS duration ≤ 120 ms (Φ = 0.707; p value ≤ 0.001). Conclusion: The akinetic segment on 2-dimensional echocardiogram was not matched with the latest activation sites in the LV determined by TDI in patients with ICM.

Dolichoectasia in vertebrobasilar arteries presented as transient ischemic attacks: A case report.

BACKGROUND: Vertebrobasilar dolichoectasia (VBD) is a rare vasculopathy. The etiology of this disease is unknown. Transient ischemic attacks (TIAs) of vertebrobasilar system refer to a transient (< 24 hours) lowering of blood flow in the posterior circulation of the brain. We present a case of dolichoectasia in the vertebrobasilar artery that presented with TIAs. CASE REPORT: A hypertensive 54-year-old man with true vertigo, nausea, imbalance, dysarthria, dysmetria, horizontal nystagmus, and gait ataxia was referred to Alzahra Hospital, Isfahan, Iran. The symptoms improved in the 1st day, but recurred in the 2nd day, lasting for 6-7 hours. According to clinical manifestations, a diagnosis of TIAs in the vertebrobasilar circulation was made. Imaging studies showed vascular anomaly. The vascular anomaly was considered as the cause of the patient's symptoms. A medical management was started using antiplatelet and antihypertensive drugs. The patient was referred for a more evaluation for other vascular anomalies. CONCLUSION: Dolichoectasia usually affects vertebral and basilar arteries and simultaneous involvement of carotid arteries is rare seen in only 0.5% of these patients. The usual symptom of dolichoectasia is ischemia and rarely hemorrhages. The most common type of ischemic stroke is lacunar type. Ischemia evolves from embolic that originate from thrombi or plaques in the walls of the ectatic artery. While hemodynamic effects are the most common cause of the presenting signs and symptoms of the anomaly. We report a case of dolichoectasia that presented with TIAs of the verterbrobasilar artery. VBD is a distinct arteriopathy known as stroke risk.

Long-term clinical outcomes of the left ventricular thrombus in patients with ST elevation anterior myocardial infarction.

BACKGROUND: This study was performed to determine the size of left ventricular thrombus (LVT), risk of systemic embolization and response to medical treatment during 18 months of follow up in the patients with anterior-ST elevation myocardial infarction (aSTEMI). METHODS: This cross-sectional study was performed on thirty-five patients with anterior myocardial infarction (MI), in Emam Reza Hospital and Ghaem Hospital, Mashhad, Iran, from August 2008 to January 2011. Warfarin was prescribed for all the patients. Transthoracic echocardiographic study was performed on the 1st, 2nd, 4th, 6th, 12th and 18th months. Outcomes included rate of death, MI, stroke, systemic embolization, major bleeding and change in thrombus size following treatment. RESULTS: The resolve rate of clot on the 2nd, 4th, 6th, 12th and 18th months was 64.7, 86.6, 81.4, 81.4 and 100 percent, respectively. In five patients with complete clot resolution, clot reformation occurred after warfarin discontinuation. In these patients, left ventricular ejection fraction (LVEF) improvement was poor. During the study period, five patients died due to severe heart failure. One patient developed hematuria whereas non-experienced thromboembolic events. The mean LVEF at study initiation was 30.8 ± 0.92%, which improved to 42 ± 0.84% (P < 0.05) at the end. CONCLUSION: All LVT was resolved with a combination therapy of antiplatelet and warfarin without any thromboembolic event. In patients with a poor improvement in the LV function, due to the risk of LVT reformation, lifelong warfarin therapy was recommended.

Comparison between theophylline, N-acetylcysteine, and theophylline plus N-acetylcysteine for the prevention of contrast-induced nephropathy.

BACKGROUND: Few studies compared the efficacy of theophylline with N-acetylcysteine or evaluated the efficacy of combination therapy in the prevention of contrast-induced nephropathy (CIN). We compared the efficacy of theophylline, N-acetylcysteine, and the combination of these agents in the prevention of CIN. METHODS: This randomized controlled trial was conducted on 96 patients referring consecutively to the Shahid Chamran University Hospital in Isfahan, Iran, for elective coronary angiography (with our without angioplasty). Patients with at least moderate risk for CIN were included and were randomized to receive theophylline (200 mg), N-acetylcysteine (600 mg), or theophylline + N-acetylcysteine, twice a day, from 24 h before to 48 h after administration of the contrast material. A non-ionic, low-osmolar contrast material was used. Serum creatinine was measured before and 48 h after contrast material injection. RESULTS: Serum creatinine was increased by 6.83 ± 15.32% with theophylline, 13.09 ± 14.63% with N-acetylcysteine, and 5.45 ±1 3.96% with theophylline + N-acetylcysteine after contrast material injection (between group P = 0.072). Controlling for Mehran risk score, baseline serum creatinine, and contrast volume, the change in serum creatinine level was lower with theophylline compared with N-acetylcysteine (F = 4.79, P = 0.033), and with theophylline + N-acetylcysteine compared with N-acetylcysteine (F = 5.78, P = 0.020). CIN (increase in creatinine of ≥ 0.5 mg/dl or ≥ 25% from the baseline) was occurred in 20%, 21.9%, and 7.1% of patients in the theophylline, N-acetylcysteine, and theophylline + N-acetylcysteine groups, respectively (P = 0.260). CONCLUSION: Theophylline is superior to N-acetylcysteine in preventing contrast-induced renal dysfunction, but the combination with N-acetylcysteine is not superior to theophylline alone in this regard. Further trials with larger sample of patients are warranted.

Cardiovascular effects of fingolimod: A review article.

Multiple sclerosis (MS) is a chronic auto-immune disease. Most therapeutic strategies for treatment of this disease direct immune modulation and control of inflammatory processes. First-line therapeutic agents showed moderate efficacy and frequent side-effects with moderate efficacy in trials. Their parental administration and limited long-term adherence restrict their efficacy compared with second-line therapies. Fingolimod as a second-line therapeutic agent has been shown to reduce annualized relapse rate, risk of disability progression and inflammatory activity of relapsing MS. Safety and efficacy FTY720: Safety and efficacy issues are the main metrics for judgment of drug efficacy. In this article, we focus on cardiovascular effects of FTY720 treatment. Effect of FTY720 on rate and rhythm, impact of FTY720 on endothelial cells, its atheroprotective effects, its effects on cardiac transplantation outcomes, vascular complications of FTY720, effects of FTY720 on endocrine functions and interaction of FTY720 with cardioactive agents are explained in this review article.

Safety of herbal medicine in treatment of weight loss.

BACKGROUND: Obesity is a common health problem in both developed and developing countries. There are many unconventional therapies, including herbal medicine, to treat this condition. Some people believe that herbal medicines are safe. This case and review is about adverse complication of treating obesity with some herbal medicine. CASE REPORT: A 19 year old male with sever obesity (120 kg) used green tea (15 cups of green tea per day) and an intensive dietary regimen to lose weight. He lost 30 kg after 2 months. At that time, one day after usual exercise he suddenly lost consciousness due to left ventricular fibrillation. CONCLUSION: Use of herbal medicine for weight reduction is not always safe. Moreover, for some herbal medicine the risk is sufficient to shift the risk-benefit balance against the use that medicine.

Serum uric acid level and its association with cardiometabolic risk factors in prediabetic subjects.

BACKGROUND: Excess serum uric acid (UA) accumulation can lead to various diseases. Increasing evidences reveal that UA may have a key role in the pathogenesis of metabolic syndrome. Little is known about the associations of UA levels with cardiometabolic risk factors in prediabetic individuals. This study was designed to evaluate the association between UA and cardiometabolic risk factors in prediabetic subjects with family history of diabetes compared with those with normal glucose tolerance (NGT). MATERIALS AND METHODS: In a cross-sectional setting, a sample containing 643 (302 prediabetic subjects and 341 normal) of the first-degree relatives of diabetic patients aged 35-55-years old were investigated. Samples were assessed in prediabetic and normal groups using glucose tolerance categories. Prediabetes was defined based on American Diabetes Association (ADA) criteria. Body weight and height, systolic and diastolic blood pressure (SBP and DBP), UA, creatinine (Cr), albumin (Alb), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and lipid profiles were measured and compared between two groups. RESULTS: Prediabetic persons were older and obese than normal persons. Also, prediabetic persons (5.2 ± 1.3 mg/dl) had significantly higher UA than normal persons (4.9 ± 1.4 mg/dl) (P < 0.05). FBG after 0, 30, 60, and 120 min in prediabetic were higher than normal persons (P < 0.001). With respect to metabolic parameters, the patients in the higher UA quartiles exhibited higher levels of body mass index (BMI), SBP, FBG and triglycerides (TG). The higher quartiles of UA tended to be associated with higher BMI and higher total cholesterol (TC) in females prediabetic persons. Based on logistic regression analysis in different models, UA was positively (odds ratio (OR) >1, P < 0.05) associated with glucose tolerance categories. This association remained statistically significant after adjusting the effects of age and BMI. Also, the association between glucose tolerance categories and UA were positively significant in both genders. CONCLUSION: High UA level was associated with some cardiometabolic risk factors in prediabetic individuals compared with normal person. UA level was also a significant predictor for prediabetes condition.

Mandibular anterior nutrient canals in periapical radiography in relation to hypertension.

BACKGROUND: Hypertension (HTN) is the most commonly encountered systemic disease in general population. Nutrient canals contain blood vessels and nerves that mostly appear in the anterior mandibular region. Nutrient canals are not detected in radiographs of all patients, and their normalcy is controversial by many investigators. OBJECTIVES: The present study investigated the correlation between the appearance of nutrient canals and hypertension as a potential clue to diagnose patients with hypertension. PATIENTS AND METHODS: Thirty two patients with HTN and 32 normotensive subjects were selected. Periapical radiographs were taken from mandibular anterior cuspid-central incisor region since nutrient canals are commonly observed in this area. Data was analyzed by SPSS software with Chi-square and Fisher tests. RESULTS: The incidence of nutrient canals was 37.5% in patients with hypertension and 53.1% in the normotensive subjects, but this difference was not statistically significant (P = 0.209). We did not find any association between duration of hypertension (P = 0.292) or controlled hypertension (P = 0.144), and the presence of nutrient canals. The mean of subject age with nutrient canal was more than those without nutrient canals, and this difference was statistically significant in normotensive patients. CONCLUSIONS: This study revealed that there was no significant association between mandibular anterior nutrient canals and hypertension.

One decade "narcotic addicted patients with deep vein thrombosis" in st. Alzahra hospital of isfahan, iran.

BACKGROUND: Behavior and substance addiction is one of the risk factors for deep vein thrombosis (DVT). The aim of this study investigating the relationship between the different clinical manifestations pattern of DVT with the way, the amount and duration of narcotic drugs in patients admitted to St. Alzahra Hospital in Isfahan, Iran, during 10 years. METHODS: In a cross-sectional study we studied all of the patients with DVT in St. Alzahra Hospital since 2003-2013 were studied. FINDINGS: A total of 238 (59.1%) of the patients were male and 165 (40.9%) female. The mean age of men and women were 18.80 ± 48 and 19.60 ± 3.48 years old. The mean length of staying in the hospital was 5.40 ± 7.20 days. Addiction among patients with DVT was 19.1%. 28.2% of men suffered from DVT and 6% of the women were drug addicts (P < 0.001). Among the 77 patients taking the drug, 53.2% were heroin, 35.1%opium, and 11.7% used other injectable drugs. The results showed that 19 patients (28.6%) were taking the drug once daily, 27.3% twice a day, 6.5% three times a day, 15.6% once a week, and 26% taking the drug twice a week. From 403 patients, 2.2% had a problem in the upper limb, 44.4% in the left hand, and 55.6 in the right hand. The results showed that none of the 77 studied patients had involvement of upper limbs, but all of them in the lower limb. About 11.2% of studied patients were addicted to injective drugs. Also, 6% were addicted to non-injectable drugs and 2% to both injectable and non-injectable drugs. CONCLUSION: DVT has many risk factors and addiction and intravenously (IV) drug abuse one of the most important for this illness and this problem mast be noticed by health worker and physicians.

An observational study on infective endocarditis: a single center experience.

BACKGROUND: Cloning of microorganisms on heart endothelium can lead to infective endocarditis (IE). The prototypic lesion of infective endocarditis, the vegetation is a mass of platelets, fibrin, microcolonies of microorganisms, and scant inflammatory cells. OBJECTIVES: The aim of this study was to evaluate patients with IE and also focusing on echocardiographic data and comparison between TTE (transthoracic echocardiography) and TEE (transesophageal echocardiography) of native and prosthetic valve endocarditis and the final impact of IE (infective endocarditis) in these patients with endocarditis. PATIENTS AND METHODS: All patients with IE admitted to our center between 2007 and 2010 were studied. All echocardiographies were performed by the same echocardiographer. Echocardiography and lab tests were performed for all patients. We used SPSS 16 for data analysis. RESULTS: We studied 35 patients, 45% male and 55% female with a mean age of 56.36 ± 12.44 years. Fever (80%) and chills (65.7%) were the most common symptoms. There was only a positive blood culture and enterococci sensitive to vancomycin and amoxicillin. The most involved valve was mitral (54.2%) and then aortic valve (48.5%) (two patients had vegetation on both aortic and mitral valves). In this study, specificity and sensitivity of TEE were 100% and 88.6%. Six patients (17.1%) died and six patients needed surgery. CONCLUSIONS: Endocarditis is an important disease with a high mortality rate if not treated appropriately. Therefore, these patients need more attention. In echocardiography, vegetation and complications of IE such as abscess and paravalvular leakage can be detected.

Aortic valve streptococcus group B endocarditis post-extracorporeal shock wave lithotripsy.

BACKGROUND: Sub-acute left-sided bacterial endocarditis is a serious condition that may present with variable clinical manifestations. Its symptoms include both sterile and infected emboli, and various immunological phenomena. CASE REPORT: This report presents a 55 year old man with frequency and dysuria after a lithotripsy and several admissions with urosepsis. Due to the suspicion of infective endocarditis echocardiography was done which confirmed streptococcus group B endocarditis. CONCLUSION: Streptococci group B is one of the rare causes of infective endocarditis, but it was observed after various producers such as lithotripsy.