Effect of Fixed-dose Combination Amlodipine/Valsartan in Comparison to Two Drug Combination Nebivolol/Valsartan on 24-Hour Ambulatory Blood Pressure.

BACKGROUND: Nebivolol has a dual mechanism of action, exerting a moderate b- blockade effect and reducing peripheral arterial resistance, as a result, the antihypertensive effect of nebivolol may be higher than that of a potent vasodilator CCB such as amlodipine. AIM: The study evaluated the effect of two nebivolol/valsartan on 24 hour ambulatory blood pressure versus amlodipine/valsartan in grade II or III hypertension patients or having uncontrolled BP despite treatment. Ambulatory blood pressure monitoring is a powerful method to monitor the changes in blood pressure over the 24 hour. MATERIALS AND METHODS: A total of 74 from 90 patients continued the study. Fourty patients received amlodipine 10 mg/valsartan 160 mg (group I), and thirty-four patients received nebivolol 5 mg/ valsartan 160 mg (group II). Peripheral blood pressure readings were measured at randomization at 6 and 12 weeks. Ambulatory blood pressure was measured at randomization and 12 weeks. RESULTS: Both drug combinations showed high efficacy in reducing peripheral and 24 hour ambulatory BP. There was no statistically significant difference between the groups in lowering peripheral systolic and diastolic blood pressure at 6 and 12 weeks. Furthermore, both groups failed to show any significant difference in reducing 24 hour SBP and DBP. Regarding day SBP, the blood pressure dropped by -5.63 ± 14.87 in group I and -6.25 ± 11.59 in group II (p = 0.844). Also, group I reduced the day DBP average by -2.53 ± 9.83 and group II by -3.61 ± 9.78 (p = 0.640). In addition, both drug combinations had no statistically significant difference in lowering night SBP and DBP average. CONCLUSION: Both treatment groups reached the target ambulatory blood pressure, and there was no statistically significant difference between both groups as a regard reduction in all ambulatory blood pressure readings.

Warfarin-Rifampin-Gene (WARIF-G) Interaction: A Retrospective, Genetic, Case-Control Study.

Warfarin is extensively metabolized by cytochrome P450 2C9 (CYP2C9). Concomitant use with the potent CYP2C9 inducer, rifampin, requires close monitoring and dosage adjustments. Although, in theory, warfarin dose increase should overcome this interaction, most reported cases over the last 50 years have not responded even to high warfarin doses, but some have responded to modest doses. To investigate the genetic polymorphisms' impact on this unexplained interpatient variability, we performed genotyping of CYP2C9, VKORC1, and CYP4F2 for warfarin and rifampin concomitant receivers from 2016 to 2022 at Hamad Medical Corporation, Doha, Qatar. We identified and included 36 patients: 22 responders and 14 nonresponders. Warfarin-responders were significantly more likely to have one or more warfarin-sensitizing CYP2C9/VKORC1 alleles than nonresponders (odds ratio = 23.2, 95% confidence interval = 3.2-195.6; P = 0.0001). The mean genetic-based pre-interaction calculated dose was significantly lower for responders than for nonresponders (P < 0.001); and was negatively correlated with warfarin sensitivity index (WSI) (r = -0.58; P = 0.0002). The median percentage time in therapeutic range and mean WSI were significantly higher in the warfarin-sensitizing CYP2C9/VKORC1 alleles carriers than noncarriers (P = 0.017 and 0.0004, respectively). Whereas the warfarin-sensitizing CYP2C9/VKORC1 genotypes were associated with modest on-rifampin warfarin dose requirements, the noncarriers would have required more than double these doses to respond. Warfarin-sensitizing CYP2C9/VKORC1 genotypes and low genetic-based warfarin calculated doses were associated with higher warfarin sensitivity and better anticoagulation quality in patients receiving rifampin concomitantly.

Target Blood Pressure and Combination Therapy: Focus on Angiotensin Receptor Blockers Combination with Either Calcium Channel Blockers or Beta Blockers.

BACKGROUND: The target blood pressure has changed many times in the guidelines in past years. However, there is always a question; is it good to lower blood pressure below 120/80 or not? Control of blood pressure in hypertension is very important in reducing hypertension-modified organ damage. So, the guidelines recommend combining more than one antihypertensive drug to reach the target blood pressure goal. RESULTS: Combination therapy is recommended by guidelines to reach the blood pressure goal. The guidelines recommend many combinations, such as the combination of angiotensin receptor blockers with either calcium channel blockers (CCB) or beta-blocker (BB). Angiotensin receptor blocker (ARB) combination with CCB has gained superiority over other antihypertension drug combinations because it reduces blood pressure and decreases the incidence of CV events and organ damage. BB combinations are recommended by guidelines in patients with ischemic events but not all hypertensive patients. Unfortunately, the new generation BB, for example, nebivolol, has a vasodilator effect, making it new hope for BB. CONCLUSION: Combination therapy is a must in treating the hypertensive patient. The new generation BBs may change the recommendations of guidelines because they have an effect that is similar to CCBs.

Sonographic reference values of cranial nerve size: A systematic review and meta-analysis.

INTRODUCTION/AIMS: Ultrasonography of the cranial nerves has recently gained attention for assessment of inflammatory, compressive, or degenerative neuropathies. However, sonographic reference values of cranial nerves have received less attention than those of peripheral nerves. In this systematic review and meta-analysis we aimed to provide current evidence of sonographic reference values for cranial nerve size. METHODS: By searching Medline (via PubMed), Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, we conducted a systematic review and meta-analysis of studies that reported ultrasound measurements of the facial, spinal accessory, and hypoglossal nerves in healthy adults. We included studies that reported either the sonographic cross-sectional area (CSA) or the nerve diameter; the included nerves were subgrouped according to the site of nerve measurement. RESULTS: Fourteen studies with a total of 661 participants and 1437 ultrasound nerve measurements met the inclusion criteria. The anatomical sites for each nerve were combined to provide single-nerve mean measurements. We found an overall mean nerve diameter of 0.80 mm for the facial nerve, 0.63 mm for the spinal accessory nerve, and 1.82 mm2 for hypoglossal nerve CSA. DISCUSSION: This meta-analysis provides reference values for the diameter and cross-sectional area of the facial, spinal accessory, and hypoglossal nerves at different sites, which can be used as guidance in clinical practice to detect pathological changes in cranial nerve size in cranial neuropathies. We recommend further validation in large-scale studies as well as standardization of the scanning protocols.

Effect of Amlodipine/Nebivolol combination therapy on central BP and PWV compared to Amlodipine/Valsartan combination therapy.

BACKGROUND: Pulse wave velocity (PWV) and central blood pressure (CBP) have been intoduced into managment of hypertensive patients. PWV is positively correlated with arterial wall stiffness while central aortic pressure becomes better predictor of cardiovascular outcome than peripheral pressure. Reduction in CBP provides protective properties against subclinical organ damage. This work aims to investigate the effect of a new combination therapy of Amlodipine/Nebivolol (A/N) on central BP, peripheral BP and PWV. The results of using this combination will be compared to the well-established fixed-dose combination of Amlodipine/Valsartan (A/V). The study conducted between October 2018 and August 2020. One hundred and two hypertensive patients were assigned for Amlodipine 10 mg/Valsartan 160 mg combination therapy (A/V, n = 52) or Amlodipine 10 mg/Nebivolol 5 mg combination therapy (A/N, n = 50) by simple 1:1 randomization. Office, central blood pressure and PWV were measured on first (0 week), second (4-8 weeks) and third visit (10-12). Difference in BP (in each arm and between arms) was calculated along all visits. RESULTS: No statistical significant difference was found between A/V and A/N regarding age, gender, BMI and CV history. OBP, CBP and PWV were significantly reduced in each arm, but no differences were found when comparing both arm results to each other. Recorded side effects were insignificant. CONCLUSIONS: The new combination therapy Amlodipine/Nebivolol (A/N) affords a significant reduction in CBP, PBP and PWV with minor and tolerable side effects. It has provided comparable results to Amlodipine/Valsartan (A/V) combination therapy.

Clinical and hemodynamic effects of oral sildenafil on biventricular function on patients with left ventricular systolic dysfunction.

BACKGROUND: We explore the dual benefits of sildenafil on bi-ventricular functions in the form of improvement of ejection fraction, pulmonary vascular resistance and functional capacity of systolic heart failure patients either related to dilated or ischemic cardiomyopathy. AIM OF THE WORK: To evaluate the effect of oral sildenafil on biventricular function in patients with left ventricular systolic dysfunction. PATIENTS AND METHODS: The prospective randomised case-control study included 80 patients with left ventricular systolic dysfunction resulting from dilated or ischemic cardiomyopathy were equally randomised to one of the treatment groups in (1:1) who were collected from the outpatient clinic of cardiac care unit (CCU) of Beni-Suef University hospital; each group contained 40 patients: The first group (control group): received the guideline-recommended treatment of heart failure with reduced ejection fraction which consists of [angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), beta-blockers, aldosterone receptor antagonist, digoxin]. The second group (sildenafil group): received the previously mentioned guideline-recommended treatment in the control group plus sildenafil 25 mg three times per day. All patients were subjected to detailed history taking, baseline transthorathic echocardiography and exercise ECG using the Naughton protocol. Follow-up transthorathic echocardiography and exercise ECG was conducted after 3 months. RESULTS: Sildenafil improves heart failure symptoms such as dyspnea or orthopnea or increasing the functional capacity of myocardium which is measured by estimated metabolic equivalents of task (METS) (P = .017), and exercise duration (P = .013). Sildenafil increased cardiac output (P = .033), which is considered one of the desirable targets in heart failure patients. CONCLUSION: In patients with left ventricular systolic dysfunction secondary to dilated or ischemic cardiomyopathy, relatively small doses of sildenafil significantly enhances exercise period and functional ability, with substantial improvement in left ventricular systolic function irrespective of the existence of major pulmonary hypertension.

Safety and Efficacy of Pharmaco-invasive Approach Using Streptokinase Compared With Primary Percutaneous Coronary Angiography.

BACKGROUND: Fibrin-specific fibrinolytics are preferred when they used in STEMI patients (pharmaco-invasive approach). However, streptokinase is still the most common used thrombolytic agent in Egypt because of its cheaper cost. METHODS: 266 STEMI patients were randomly assigned to undergo PPCI or pharmacoinvasive (using streptokinase). Primary end point (death, shock, congestive heart failure, or reinfarction up to 30 d) and secondary end point (ischemic stroke, intracranial hemorrhage, or nonintracranial bleeding) were followed for 30 days after reperfusion. In pharmaco-invasive arm, urgent coronary angiography was performed in case of failed reperfusion. Based on the reperfusion time from symptoms onset, patients in both arms were divided into; early (≤3 hrs) and late reperfusion (>3 hrs). RESULTS: No statistical significant difference regarding left ventricular ejection fraction, end diastolic and end systolic diameter in both arms. Early PPCI (≤3 hrs) had highest ejection fraction values (56.9 ± 7.5). Myocardial wall preservation was best achieved in early pharmaco-invasive (≤3 hrs).There was no statistical significant difference in TIMI flow results between all subgroups (early and late of both arms) (P = 0.750). Suction devices and IV Eptifibatide were less frequently used in the pharmaco-invasive comparing to PPCI arm; (P = 0.000 and P = 0.006) subsequently. No statistical significant difference regarding complication incidence in both arms (P = 0.518). Radial access was more commonly used in the pharmaco-invasive arm (P = 0.015). CONCLUSION: Utilizing streptokinase in early re-perfused patients by PI approach (≤3 hrs) seems safe and efficient when PPCI delay (>120 min from symptom onset) is the other option.

Effects of dexamethasone on foetal Doppler flow velocimetry.

Corticosteroid administration before anticipated preterm birth is a well known antenatal therapy available to improve newborn outcomes. Doppler studies of maternal and foetal vessels provide a way to understand how corticosteroid affects and improves foetal respiratory outcome. This study was registered on 8th of October, 2017 by Menoufia Faculty of Medicine Board with registration number 222-2-10-2017. It included 80 pregnant women divided into two groups. Each group consisted of 40 participants. Group A: participants were between 28 weeks and 34 weeks of gestation and were at risk of preterm labour. Group B: participants were those who had undergone an elective caesarean section (CS) before completing the 39th week of gestation. Each woman had received four doses of Dexamethasone 6 mg intramuscularly, 12 h apart. Doppler studies were performed before the Dexamethasone adminstration and 24 h after the Dexamethasone course. Among both groups, only pregnant women before 34 weeks of gestation showed a significant decrease in middle cerebral artery pulsatility index. However, the other Doppler parameters showed no significant effect. In conclusion, Dexamethasone administration affected only the middle cerebral artery pulsatility index before 34 weeks of gestation.IMPACT STATEMENTWhat is already known on this subject? Preterm births account for 75% of neonatal morbidity and pulmonary dysfunction plays an important role on such morbidities. Also, neonates born after an elective CS have significantly higher rates of respiratory morbidity and neonatal intensive care unit admission. Corticosteroids are wildly used to improve neonatal outcome in women who have expected preterm labour and before an elective CS.What do the results of this study add? Dexamethasone affected blood distribution of foetal brain only before 34 weeks of gestation that had been proved by changes of foetal middle cerebral artery pulsatility index without affecting other Doppler parameters of both groups. With the improvement of foetal respiratory outcome in both groups.What are the implications of these finding for clinical practice and/or further research? Maternal Dexamethasone injection is recommended for mothers at risk of preterm labour, especially if delivery is expected within six days and mothers who will undergo elective CS before completion of 39 weeks of gestation, in terms of improving neonatal respiratory functions and decreasing the possibility of admission to neonatal intensive care unit for transient tachypnoea of the newborn.

Percutaneous trans-ulnar versus trans-radial arterial approach for coronary angiography and angioplasty, a preliminary experience at an Egyptian cardiology center.

BACKGROUND: Trans-ulnar approach was proposed primarily for elective procedures in patients not suitable for trans-radial approach that was introduced two decades ago. The trans-ulnar approach is as safe and effective as the trans-radial approach for coronary angiography and intervention. AIM: This study's aim was to assess the feasibility and safety of the trans-ulnar approach in coronary procedures as a preliminary experience for operators experienced in trans-radial approach with no/minimal trans-ulnar approach experience at an Egyptian center. RESULTS: Vascular access in 120 patients was selected randomly for coronary angiography and angioplasty-80 through radial and 40 through ulnar approach. Patients were examined for local complications and Doppler evaluation to both radial and ulnar arteries a day after the procedure was done. Ulnar approach success was 82.5% versus 93.7% in the radial group; failure of ulnar artery puncture was the only cause of crossover in the ulnar group, while occurrence of persistent spasm was the leading cause of crossover in the radial group followed by radial artery tortuosity. The procedure time of coronary angiography and percutaneous coronary intervention of the ulnar group was significantly higher than that of the radial group (P value = 0.011 and 0.034, respectively). The mean caliber of the right ulnar artery was 2.45 ± 0.38, slightly larger than that of the radial artery 2.33 ± 0.38 at the level of the wrist, but this difference was statistically non-significant. CONCLUSION: Our study demonstrated that ulnar access with experienced radial operators and in our patients is a safe and practical approach for coronary angiography or angioplasty, without any major complications. Bearing in mind its high success rate, it can be used when a radial artery is not useful for the catheterization or as a default approach on the expense of slightly longer procedural time.

Exercise augments the modulatory effects of vitamin E on pre-diabetes-induced aortopathy: a potential role of adiponectin.

Background: We tested the hypothesis that vitamin E may protect against pre-diabetes-induced aortic injury (aortopathy), and exercise can augment the action of vitamin E.Material and methods: Rats were either fed with a high fat and fructose diet (HFD) (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. The three protective groups were treated with vitamin E (HFD + Vit E), swimming exercises (HFD + Ex), and vitamin E plus swimming exercises (HFD + VitE + Ex), respectively.Results: Aortopathy was developed in the model group as demonstrated by substantial tissue ultrastructural alterations, which were partially protected by vitamin E and effectively protected with vitamin E plus swim exercise. Also, swimming exercises significantly (p < .05) increased the modulatory effects of vitamin E on dyslipidemia, insulin resistance, blood pressure, oxidative stress, inflammation, leptin, and adiponectin, except coagulation and thrombosis.Conclusions: Swim exercise augments the protective effects of vitamin E in a pre-diabetic animal model.

Additive value of 3D-echo in prediction of immediate outcome after percutaneous balloon mitral valvuloplasty.

BACKGROUND: Results of percutaneous balloon mitral valvuloplasty (BMV) are basically dependent on suitable patient selection. Currently used two-dimensional (2D) echocardiography (2DE) scores have many limitations. Three-dimensional (3D) echocardiography (3DE)-based scores were developed for better patient selection and outcome prediction. We aimed to compare between 3D-Anwar and 2D-Wilkins scores in mitral assessment for BMV, and investigate the additive value of 3DE in prediction of immediate post-procedural outcome. Fifty patients with rheumatic mitral stenosis and candidates for BMV were included. Patients were subjected to 2D- and real-time 3D-transthoracic echocardiography (TTE) before and immediately after BMV for assessing MV area (MVA), 2D-Wilkins and 3D-Anwar score, commissural splitting, and mitral regurgitation (MR). Transesophageal echocardiography (TEE) was also undertaken immediately before and intra-procedural. Percutaneous BMV was performed by either multi-track or Inoue balloon technique. RESULTS: The 2DE underestimated post-procedural MVA than 3DE (p = 0.008). Patients with post-procedural suboptimal MVA or significant MR had higher 3D-Anwar score compared to 2D-Wilkins score (p = 0.008 and p = 0.03 respectively). The 3D-Anwar score showed a negative correlation with post-procedural MVA (r = - 0.48, p = 0.001). Receiver operating characteristic (ROC) curve analysis for both scores revealed superior prediction of suboptimal results by 3D-Anwar score (p < 0.0001). The 3DE showed better post-procedural posterior-commissural splitting than 2DE (p = 0.004). Results of both multi-track and Inoue balloon were comparable except for favorable posterior-commissural splitting by multi-track balloon (p = 0.04). CONCLUSION: The 3DE gave valuable additive data before BMV that may predict immediate post-procedural outcome and suboptimal results.

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats.

BACKGROUND: The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury. AIM: In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury. METHODS: Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed. RESULTS: Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers. CONCLUSION: In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.

Postoperative Serum Troponin Trends in Infants Undergoing Cardiac Surgery.

Troponin-I (TN-I) levels are elevated following pediatric cardiac surgery with speculation that particular patterns may have prognostic significance. There is lack of procedure-specific data regarding postoperative TN-I levels in infants undergoing cardiac surgery. We hypothesized that TN-I elevation varies with type of surgery and persistent elevation predicts poor prognosis. We prospectively measured serial TN-I levels (preoperatively, 4, 8, 12, 24, and 48 hours postoperatively) in 90 infants (age < 1 year) undergoing cardiac surgery: off cardiopulmonary bypass (CPB) (n = 15), on CPB (n = 43), and on CPB with ventricular incision (CPB with ventricular incision; n = 32). All patients had undetectable baseline TN-I levels. The area under the curve of TN-I levels over the 48-hour period was significantly different among the surgical groups (P < 0.002), and highest in patients with CPB with ventricular incision. Generally, TN-I levels peaked by 4 hours after surgery and returned to near-normal levels within 48 hours. A persistent TN-I rise beyond 8 hours after surgery was a strong predictor of postoperative hypoperfusion injury (defined as a composite endpoint of end-organ injury resulting from inadequate perfusion, odds ratio 21.5; P = 0.001) and mortality (30% in those with persistently high TN-I, compared with 3.5% in the remaining patients; P < 0.001), independent of patient age, anatomy and/or complexity of surgery, and level of postoperative support. Our data provide benchmark values for TN-I levels following cardiac surgery in infants. Extent of TN-I elevation correlates with type of surgery. Persistent TN-I elevation beyond 8 hours after surgery is strongly associated with postoperative hypoperfusion injury and mortality.

Effect of Amlodipine/Valsartan Versus Nebivolol/Valsartan Fixed Dose Combinations on Peripheral and Central Blood Pressure.

INTRODUCTION: Although hypertensive drugs may have the same effect on peripheral blood pressure, they vary in their effect on central blood pressure and its indices. AIM: To evaluate efficacy of fixed-dose combination of amlodipine 10 mg/valsartan 160 mg versus nebivolol 5 mg/valsartan 160 mg in grade 2 or more hypertensive patients assessed by peripheral and central blood pressure. METHODS: A prospective, open label, randomized study done in the outpatient cardiology clinic at Beni-Suef University Hospital. A total of 137 patients continued the study; group I (n = 75) received Amlodipine 10 mg/Valsartan 160 mg (A/V) and group II (n = 62) received Nebivolol 5 mg/Valsartan 160 mg (N/V). Peripheral, central blood pressure and its indices were measured at baseline, after 6 and 12 weeks. RESULTS: The two combinations reduced peripheral and central BP (P < 0.0001) after 6 and 12 weeks. A/V combination significantly reduces central Pulse Pressure (PP) after 6 and 12 weeks (- 8.53 ± 13.80 and - 10.17 ± 11.29 (P < 0.0001) respectively), while N/V showed its efficacy in reducing central PP after 12 weeks (- 7.03 ± 13.10, P = 0.005). A/V combination was more effective in reducing Pulse Wave Velocity (PWV) after 6 and 12 weeks; P < 0.0001 vs P = 0.004. After 6 weeks, N/V was more effective in reducing Augmentation Index (AIx) (- 6.00 ± 10.94 (P = 0.002) vs. - 3.44 ± 9.80 (P = 0.026)) while after 12 weeks A/V did not show any significance (P = 0.085). CONCLUSIONS: Both treatment groups lowered patients' peripheral, central blood pressure after 6 and 12 week of treatment, but Amlodipine/Valsartan combination was more effective. Both treatments exerted different effects on central indices.

Involvement of brain natriuretic peptide signaling pathway in the cardioprotective action of sitagliptin.

BACKGROUND: The current study is focusing on the role of brain natriuretic peptide (BNP), a substrate of dipeptidyl peptidase-4 (DPP-4) enzyme, and its signaling survival pathway in the cardioprotective mechanism of sitagliptin, a DPP-4 inhibitor. METHODS: Male Wistar rats were randomized into 7 groups, sham, I/R, KT-5823 (selective protein kinase (PK) G inhibitor), 5-HD (selective mito-KATP channel blocker), sitagliptin (300mg/kg, po), sitagliptin+KT-5823, and sitagliptin+5-HD. Sitagliptin was administered for 3 days prior to induction of coronary I/R, while either KT-5823 or 5-HD was administered intravenously 5min before coronary ligation. RESULTS: Pretreatment with sitagliptin provided significant protection against I/R injury as manifested by decreasing, percentage of infarct size, suppressing the elevated ST segment, reducing the increased cardiac enzymes, as well as DPP-4 activity and elevating both heart rate (HR) and left ventricular developed pressure (LVDP). However, the addition of either blocker to sitagliptin regimen reversed partly its cardioprotective effects. Although I/R increased BNP content, it unexpectedly decreased that of cGMP; nevertheless, sitagliptin elevated both parameters, an effect that was not affected by the use of the two blockers. On the molecular level, sitagliptin decreased caspase-3 activity and downregulated the mRNA levels of BNP, Bax, and Cyp D, while upregulated that of Bcl2. The use of either KT-5823 or 5-HD with sitagliptin hindered its effect on the molecular markers tested. CONCLUSIONS: The results of the present study suggest that the cardioprotective effect of sitagliptin is mediated partly, but not solely, through the BNP/cGMP/PKG survival signaling pathway.

Transradial artery approach in STEMI patients reperfused early and late by either primary PCI or pharmaco-invasive approach.

The purpose of the study was to investigate the safety and efficacy of transradial artery approach (TRA) in STEMI patients who reperfused early (≤3 h from symptoms onset) or late (>3 h from symptoms onset) by either PPCI or pharmaco-invasive strategy (PI), thrombolysis followed by CA. Therefore, a total 143 STEMI patients (who were presented within 12 h from symptoms onset or 12-24 h with an evidence of ongoing ischemia or suffered from an acute STEMI were randomized for either PI or PPCI. Eighty-two patients were assigned to PI arm while the rest assigned were to PPCI arm. Patients who were taken to a non-PCI capable hospital received streptokinase and were then transferred to our Hospital for CA. TRA was used in the catheterization laboratory for all patients. Each arm was divided according to reperfusion time into early and late subgroups. A primary endpoint was death, shock, congestive heart failure, or reinfarction up to 30 days. There was a non-significant difference regarding LVEF in both arms. Myocardium wall preservation was significant in the early PI arm (P = 0.023). TIMI flow had no discrepancy between both arms (P = 0.569). Mean procedural and fluoroscopic time were 35.1 ± 6.1 and 6.3 ± 0.9 min. There were no reported entry site complications. There was no difference in primary endpoint complications (P = 0.326) considering the different times of patients' reperfusion (early; P = 0.696 vs. late; P = 0.424). In conclusion, it is safe and effective to use TRA in STEMI patients who reperfused by either early or late PPCI or PI. We recommend PI for STEMI patients with delay presentation if PPCI is not available.

Trends in oral anticoagulant use in Qatar: a 5-year experience.

In Qatar, dabigatran was introduced in 2011 followed by rivaroxaban in 2014. In this study, we aim to explore the trends in oral anticoagulant use in Qatar over the past 5 years and to what extent did DOACs replace warfarin. We also explored the extent of switching between different anticoagulants (from warfarin to DOACs and vice versa). We collected all anticoagulant prescriptions dispensed as in- or out-patient from 2011 to 2015 in all Hamad Medical Corporation (HMC) hospitals. Overall number of patients using warfarin, dabigatran and rivaroxaban over the last 5 years collectively was calculated. Per each calendar year, we calculated the number of all 3 OAC used (warfarin, dabigatran and rivaroxaban), frequency of use of each one of the OAC prescribed and compared the change in proportion of DOACs to warfarin prescriptions over the years. Overall, 6961 patients were using OAC over the past 5 years among which 5849 (84%) used warfarin, 496 (7.1%) used dabigatran and 616 (8.8%) used rivaroxaban. Oral anticoagulants use increased gradually from 2091 in 2011 to 3688 in 2015. Number of patients receiving DOACs increased significantly compared to warfarin [11 (0.5%) in 2011 vs. 849 (23%) in 2015 (p < 0.0001)]. Since its introduction in 2014, number of rivaroxaban users increased significantly compared to dabigatran [212 (40.9%) in 2014 vs. 544 (64.1%) in 2015]. DOACs have been gradually replacing warfarin in Qatar and the trend of their use is similar to that reported in other countries. Warfarin remains the most commonly used oral anticoagulant.

Survival and quality of life for children with end-stage heart failure who are not candidates for cardiac transplant.

BACKGROUND: Some pediatric patients referred for heart transplant (HTx) are sub-optimal candidates. Their outcomes without HTx are presumed to be dismal, but have not been well described. Knowledge about their outcomes is critical when weighing the risks between a high-risk transplant and "terminal" palliation. METHODS: We retrospectively reviewed all HTx referrals from January 2005 to July 2013. We excluded those who were listed for HTx, or who were denied HTx due to being "too well," seeking only those who were in need of but not suitable for HTx. End-points included mortality and length of survival. RESULTS: Of 212 referrals, 39 (19%) (age 0 to 19 years, median 3.5 years) were denied HTx for reasons other than being too well. Twenty-eight (72%) had palliated congenital heart disease. Overall mortality during the follow-up period was 38% (n = 15) with a median follow-up time of 195 days (8 to 2,832 days). Ten patients received subsequent cardiac surgery with 1 death (10%) and median follow-up of 2.6 years. Mortality risk was not influenced by age, weight, growth failure, congenital heart disease or single-ventricle physiology. Mechanical ventilation (hazard ratio 6.31, p = 0.001) and inotrope dependence (hazard ratio 4.79, p = 0.006) were associated with the highest risk of mortality. Quality of life was measured with the PedsQL cardiac module and completed by 11 of 16 eligible patients with an overall average score of 70.2 ± 23.9. CONCLUSIONS: An advanced heart failure program can achieve satisfactory results for pediatric patients who are not suitable candidates for HTx. For some children, high-risk palliative surgery can result in better outcome than high-risk HTx. Mortality was related to the degree of heart failure at presentation rather than underlying heart disease.