The significance of PCSK-9's level and polymorphism in premature coronary artery disease: Relation to risk and severity.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a circulating protein that plays an important role in lipid metabolism and is linked to inflammation, which has implications for atherosclerosis and its severe cardiac effects. We studied the potential association of the PCSK-9 gene single nucleotide polymorphism (SNP), Oxidized low-density lipoprotein receptor 1- (OLR-1), and caspase-3 serum levels with the risk and severity of premature coronary artery disease (PCAD). The potential contribution of PCSK-9 serum level to the severity of PCAD patients was also assessed. METHOD: This case-control study included 120 PCAD patients (age < 45), and 60 age matched healthy controls. Serum PCSK-9 and caspase-3 levels and clinical characteristics were recorded. SYNTAX score was calculated to estimate the severity of the coronary artery lesions. The SNP rs2483205 of the PCSK-9 gene and the rs11053646 of the OLR-1gene were genotyped in all participants. RESULTS: Serum PCSK-9 levels were higher in PCAD patients and were significantly different among the three SYNTAX score groups (SS ≤ 12, 12 < SS ≤ 21.5, and SS > 21.5). The diagnostic cutoff values of PCSK-9 and caspase-3 levels for PCAD were > 3.2 ng/mL for both, yielding an area under the curve (AUC) of 0.98 and 0.92, sensitivity of 85 %, 98 %, and specificity of 99.5 %, 93 % for PCSK-9 and caspase-3, respectively. The genotypes TT + CT vs. CC of PCSK-9's rs2483205 SNP presented a higher risk for PCAD and higher SYNTAX scores. Furthermore, the rs11053646 SNP of OLR-1 presented the CG genotype as more risky and having higher SYNTAX scores. CONCLUSION: Circulating PCSK9 and caspase-3 concentrations were higher in PCAD patients and were associated with CAD severity. The SNPs of PCSK-9 (rs2483205) and OLR-1 (rs11053646) were associated with PCAD and its severity.

Adherence to Quality Indicators for ST-Elevation Myocardial Infarction Management: An Egyptian Experience.

Coronary artery disease remains a significant health problem, especially in developing countries. Adherence to guideline-directed therapy improves the quality of care. In this study we assessed adherence to quality indicators (QIs) for ST-elevation myocardial infarction (STEMI) management in our center as an example from a developing country. Our study included 870 STEMI patients who were admitted to our center (Assiut University Heart Hospital, Egypt) and eligible for primary percutaneous coronary intervention during the period from January 2022 to December 2022. Fifteen QIs were studied. The results show that our center is closely adherent to STEMI management guidelines. However, the most important gaps were related to time delays. The mean of first medical contact (FMC) to electrocardiogram (ECG) time was 13.2 ± 16.1 minutes and arrival time to ECG time was 12.8 ± 3.9 minutes. The mean of FMC to device time for total patients was 61.2 ± 42.8 minutes. However, that for patients transferred from non-PCI capable center was 108.2 ± 63.5 minutes compared to patients presented directly to our center (mean arrival time to a device was around Mean 49.6 ± 22.5 minutes). This resulted in only 77% of patients having FMC to device time < 90 minutes. Regarding guideline-directed medical therapy, we are adherent by more than 90%. In-hospital mortality was 1.1%. So we conclued that many centers in developing countries are closely adherent to QIs of STEMI management. However, there are still some limitations including delays in transportation, a limited number of primary PCI centers, absence of a well-established network of communication between centers, and financial issues.

Plasma brain natriuretic peptide, D-Dimer, and serum troponin-I as predictors for in-hospital death in patients with COVID-19.

The severe acute respiratory syndrome coronavirus 2, first appeared in Wuhan, China, in December 2019. Since then, a variety of strains of the virus were spread throughout the world, prompting the World Health Organization to declare a pandemic in March 2020. Additionally, Coronavirus disease 2019 (COVID-19) can cause a variety of symptoms, ranging from fatigue and fever to severe respiratory and cardiovascular complications. This study evaluated the role of brain natriuretic peptide (BNP), troponin-I and D-dimer as biomarkers for death prediction in hospitalized patients with COVID-19. The study included 90 patients with COVID -19 diagnosed with PCR-RNA testing. They were divided into survivors and non-survivors. Also, 20 apparently healthy individuals age and sex matched were included as a control group. Plasma BNP and serum troponin-I were measured by enzyme linked immune-sorbent assay (ELISA) technique. D-dimer was measured by a turbidimetric technique. Patients with COVID-19 had significantly elevated levels of serum Troponin-I and plasma BNP in comparison to controls (p < 0.0001, for both). D-dimer, troponin-I and BNP levels were significantly higher in the non-survivors group when compared to the survivors group. Troponin-1 can predict COVID-19 severity with sensitivity, specificity, and accuracy of 55.1%, 66.7%, and 57.8%, respectively at a cutoff value of 0.075 (ng /ml); and area under the receiver operating characteristic (AUC) curve of 0.670 (95% CI: 0.551 - 0.790, p=0.018). BNP can predict COVID-19 severity with sensitivity, specificity, and accuracy of 98.6%, 71.4%, 92.2%, respectively at a cutoff value of 16.02 (Pg /ml) and AUC of 0.872 (95% CI: 0.778 - 0.965, p < 0.001). Univariate and multivariate logistic regression analysis showed that only BNP level can significantly predict death among COVID-19 infected patients. In conclusion, plasma BNP and serum troponin-I could be used as prognostic biomarkers for determination of the severity of COVID-19 and BNP could predict mortality.

Clinical course, viral etiology, and the diagnostic workup for patients with suspected myocarditis: a single-center prospective study.

BACKGROUND: Myocarditis is a highly heterogeneous disorder with a challenging diagnostic work-up. We aimed to focus on the possible diagnostic workup for this condition in settings where endomyocardial biopsy as a gold standard is not always feasible, detect the etiologic cardiotropic viruses in our locality, and follow the clinical course in patients admitted with clinically suspected myocarditis. METHODS: This is a prospective observational study. We recruited patients with clinically suspected myocarditis presenting at a university hospital from October 1st, 2020 until March 31st, 2021. All Patients had a diagnostic coronary angiography and were included only if they had a non-obstructive coronary artery disease. All patients also had cardiac magnetic resonance imaging (CMR) with contrast. Sera were obtained from all suspected patients for detection of antibodies against viruses using enzyme-linked immunosorbent assay, and viral genomes using polymerase chain reaction (PCR), and reverse transcription-PCR. Endomyocardial biopsy was done for patients with a typical CMR picture of myocarditis. RESULTS: Out of 2163 patients presenting to the hospital within the 6 months, only 51 met the inclusion criteria. Males represented 73%, with a mean age of 39 ± 16 years. CMR showed an ischemic pattern in 4 patients and thus they were excluded. We classified patients into two categories based on CMR results: group A (CMR-positive myocarditis), 12 patients (25.5%), and group B (CMR-negative myocarditis), 35 (74.5%) patients. On serological analysis, 66% of patients (n = 31/47) showed antibodies against the common cardiotropic viruses. Parvovirus B19 IgM in 22 patients (47%) and coxsackievirus IgM in 16 (34%) were the most observed etiologies. Regarding the outcome, 42.5% of patients recovered left ventricular ejection fraction and three patients died at 6 months' clinical follow-up. CONCLUSION: Patients with Clinically suspected myocarditis represented 2.2% of total hospital admissions in 6 months. CMR is only a good positive test for the diagnosis of acute myocarditis. Parvovirus B19 and coxsackievirus were the most common pathogens in our locality. TRIAL REGISTRATION: Clinical trial registration no., NCT04312490; first registration: 18/03/2020. First recruited case 01/10/2020. URL: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S0009O3D&selectaction=Edit&uid=U0002DVP&ts=2&cx=9zdfin .

Impact of atrial septal defect device size on biventricular global and regional function: a two-dimensional strain echocardiographic study.

OBJECTIVE: In this study, we assessed the acute changes in biventricular longitudinal strain after atrial septal defect transcatheter closure and its relation to the device size. METHODS: Hundred atrial septal defect patients and 40 age-matched controls were included. Echocardiography and strain study were performed at baseline and 24 hours and 1 month after the intervention. The study group was divided into two subgroups; group 1: smaller devices were used (mean device size = 1.61 ± 0.05 cm, n = 74) and group 2: larger devices were used (mean device size = 2.95 ± 0.07 cm, n = 26). RESULTS: At baseline, there was a significant difference between the study group and controls as regards right ventricular global longitudinal strain with significant hyperkinetic apex (p = 0.033, p = 0.020, respectively). There was a significant immediate reduction in right ventricular global longitudinal strain (from -24.43 ± 0.49% to -21.62 ± 0.47%, p < 0.001), which showed insignificant improvement after 1-month follow-up. While only left ventricular global longitudinal strain increased after 1 month. Within 24 hours of device closure, all the basal- and mid-lateral segments strains and apical right ventricular strains showed a significant reduction. There was a significant negative correlation between the indexed large device size and an immediate change in the right ventricular global longitudinal strain (r = -0.425, p = 0.034). CONCLUSION: Significant right ventricular global longitudinal strain reduction starts as early as 24 hours after transcatheter closure, irrespective of the device size used. The rapid impact of closure was mainly on the biventricular basal and lateral segments and right ventricular apical ones, especially with the large sized atrial septal defect.

Copeptin, miRNA-208, and miRNA-499 as New Biomarkers for Early Detection of Acute Coronary Syndrome.

cTn and CK-MB are gold standard biomarkers for acute coronary syndrome (ACS) but are less sensitive in the first 3 h after onset of symptoms. A need thus exists for novel biomarkers for early detection of ACS. We evaluated circulating copeptin, miRNA-208, and miRNA-499 as possible biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI). Sixty-five patients with probable ACS that presented within 4 h of the onset of chest pain (23 UA and 42 NSTEMI) and 25 apparently healthy individuals were studied. Two sets of blood samples collected in the first 3 h and at 6 h after onset were analyzed for copeptin levels via ELISA and miRNA-208 and miRNA-499 expression via real-time PCR. Copeptin, miRNA-208, and miRNA-499 expression levels were significantly increased in UA and NSTEMI patients compared with controls (p < 0.001) and in NSTEMT compared with UA patients (p < 0.001). Levels were also significantly elevated in UA and NSTEMI patients with negative cardiac troponin in the first 3 h (p < 0.001). ROC curves displayed AUC for prediction of ACS of 0.96 for copeptin, 0.97 for miRNA-208, and 0.97 for miRNA-499. Their combination improved AUC to 0.98. Copeptin and miRNA-208 and miRNA-499 expression are promising biomarkers for UA and NSTEMI that present in the first 3 h of pain onset. A combination of these markers with cTn may increase the accuracy of diagnosis by avoiding the gray zone of cTn as a biomarker.

Efficacy and safety of hydro-mechanical defragmentation in intermediate- and high-risk pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is the third most common acute cardiovascular syndrome. Percutaneous catheter directed hydro-mechanical defragmentation (HMD) is one of the recommended treatment options for PE in patients with contraindications to thrombolytic therapy or failed systemic thrombolysis (ST). We aimed to identify the safety and outcomes of catheter directed HMD in patients with high-risk PE. This nonrandomized controlled trial enrolled all patients with confirmed diagnoses of high- and intermediate-high-risk PE from October 2019 till January 2021. Fifty patients were included and divided into two groups by the PE response team according to the presence or absence of a contraindication for ST. Group B (ST) consists of 25 patients and group A (HMD) of 25 patients who cannot receive ST. RESULTS: The two groups were comparable regarding baseline clinical characteristics with mean age 51 ± 13 years. In group A, systolic blood pressure (BP) and oxygen saturation increased after 24 h (p = 0.002) and 48 h (p < 0.001) compared to pre-HMD procedure. Mean pulmonary artery systolic pressure (PASP) and respiratory rate (RR) decreased after 48 h and at 30 days (p < 0.001) compared to pre-HMD procedure. The increase in systolic BP and oxygen saturation were significantly higher in HMD group compared with ST group after 48 h and at 30 days (p < 0.007). The decrease in PASP and RR was significantly higher in HMD group compared to ST group after 48 h and at 30 days (p < 0.001). Mortality rate at 30 days was 20% in HMD group compared to 32% in ST group. CONCLUSIONS: Catheter directed HMD for high-risk and intermediate-high-risk PE is safe and effective with acceptable mortality Trial registration Clinical trial ID: NCT04099186.

The changes in biventricular remodelling and function after atrial septal defect device closure and its relation to age of closure.

BACKGROUND: The trans-catheter closure of atrial septal defect (ASD) usually has a rapid impact on biventricular remodelling and functions. Whether the transcatheter closure of ASD at early childhood or at adulthood age would affect the improvement in biventricular dimensions and functions remains an area of active research. RESULTS: This prospective observational study enrolled 70 subjects (50 ASD cases and 20 control subjects). Tissue Doppler imaging (TDI) and strain (S) were performed for the control group and ASD patients at baseline and at 24 h and 1 month after ASD device closure. The total ASD group was subdivided into two subgroups: group-1-children and adolescent with ASD, who underwent transcatheter closure at age ≤ 19 years; group-2-adult who underwent ASD device closure at age > 19 years old. The right and left ventricular global longitudinal systolic strain (RV/LV-GLS) and RV free wall longitudinal strain (RV free wall LS) showed a significant decline after 24 h of device closure (RVGLS-P = 0.001, LVGLS-P = 0.048, RV free wall LS-P < 0.001). However, after a 1-month follow-up, the LVGLS increased in comparison with 24 h changes after device closure (P = 0.038). The baseline mean value of RV free wall LS of G2 was significantly lower than G1 value (P < 0.001). There was no statistically significant difference between the 2 age subgroups regarding biventricular GLS and RV free wall LS changes after device closure. The changes in LV diastolic function immediately and after 1 month of device closure showed a statistically significant change in e' and its delta change value in group-2 in comparison with its baseline values and to group-1 delta changes (P = 0.002, P = 0.011, P = 0.019, respectively). CONCLUSION: The ASD transcatheter closure reduced biventricular global and RV free wall longitudinal systolic strain within 1 day of intervention and was associated with a short-term improvement in the LV-GLSS after a 1-month duration. The progressive increase in LV preload results in its strain growth and reduction in diastolic function after transcatheter ASD closure. The older age at the time of ASD device closure was associated with a significant decrease in the RV free wall LS and septal e' velocity towards abnormality.

The role of optical coherence tomography guidance in scaffold versus stent optimization.

BACKGROUND: Optical coherence tomography showed a great ability to identify adverse features during percutaneous coronary intervention with drug-eluting stents and resulted in better clinical outcomes. The study aimed to assess the impact of optical coherence tomography on intraoperative decision-making during implantation of Absorb bioresorbable scaffolds versus everolimus drug-eluting stents. RESULTS: We performed an observational study that included 223 consecutive patients post optical coherence tomography-guided implantation of either Absorb bioresorbable scaffolds (162 patients) or everolimus drug-eluting stents (61 patients). We studied the influence of optical coherence tomography on intraoperative decision-making during implantation of bioresorbable scaffolds versus drug-eluting stents by analyzing the total rate of optical coherence tomography-dependent modifications in each device. After satisfactory angiographic results, the total rate of required intervention for optical coherence tomography detected complications was significantly higher in the bioresorbable scaffolds arm compared to drug-eluting stents arm (47.8% versus 32.9%, respectively; p = 0.019). The additional modifications encompassed further optimization in the case of device underexpansion or struts malapposition, and even stenting in the case of strut fractures, or significant edge dissection. CONCLUSIONS: Compared to drug-eluting stents, Absord scaffold was associated with a significantly higher rate of optical coherence tomography-identified intraprocedural complications necessitating further modifications. The study provides some hints on the reasons of scaffolds failure in current PCI practice; it offers a new insight for the enhancement of BRS safety and presents and adds to the growing literature for successful BRS utilization.

Cardiac magnetic resonance assessment of mitral regurgitation severity appears better than echocardiographic imaging.

The mitral valve surgery decision is made mainly according to echocardiographic (ECHO) criteria. As the asymptomatic patients are still candidates for surgery in some situations, this makes the accurate assessment of mitral regurgitation (MR) severity and cardiac dimensions even more important. We aimed to compare ECHO and cardiac magnetic resonance imaging (CMR) in the assessment of MR severity and cardiac dimensions. In this prospective study, we included all patients with more than mild MR by ECHO and referred to our university hospital from 1st of April 2017 and 1st of April 2019. Exclusion criteria were critically ill patients, presence of other valve lesions, planned revascularization, pregnancy and contraindication for CMR. All patients had full history taking, examination, body surface area, and ECG. MR severity and left atrial and left ventricular dimensions were assessed in 50 patients with both 2D-ECHO and CMR in the same day. There were no significant differences in baseline clinical characteristics between moderate (24 patients) and severe MR (26 patients) groups. Poor degree of agreement was present between CMR and ECHO assessment for MR severity (same degree of MR only in 36% (18/50 patients) with kappa grade = 0.19). Furthermore, ECHO overestimated grades of MR compared to CMR (severe MR in 52% vs. 38.4%, p = 0.01 respectively). Based on the etiology of MR, primary (30 patients) vs. secondary MR (20 patients) showed the same dis-agreement between CMR and ECHO assessment of MR severity. Left atrial and ventricular dimensions showed good agreement between CMR and ECHO. Our results suggest that CMR could be more accurate than ECHO in assessing the severity of MR especially in severe cases that need surgery.

Electrocardiographic measures of ventricular repolarization dispersion and arrhythmic outcomes among ST elevation myocardial infarction patients with pre-infarction angina undergoing primary percutaneous coronary intervention.

BACKGROUND: Arrhythmias are considered one of the major causes of death in ST elevation myocardial infarction (STEMI), particularly in the early in-hospital phase. Pre-infarction angina (PIA) has been suggested to have a protective role. OBJECTIVES: To study the difference in acute electrocardiographic findings between STEMI patients with and without PIA and to assess the in-hospital arrhythmias in both groups. MATERIAL AND METHODS: We prospectively enrolled 238 consecutive patients with STEMI. Patients were divided into two groups: those with or without PIA. ECG data recorded and analyzed included ST-segment resolution (STR) at 90 min, corrected QT interval (QTc) and dispersion (QTD), T-peak-to-T-end interval (Tp-Te), and dispersion and Tp-Te/QT ratio. In-hospital ventricular arrhythmias encountered in both groups were recorded. Predictors of in-hospital arrhythmias were assessed among different clinical and electrocardiographic parameters. RESULTS: Of the 238 patients included, 42 (17%) had PIA and 196 (83%) had no PIA. Patients with PIA had higher rates of STR (p < 0.0001), while patients with no PIA had higher values of QTc (p = 0.006), QTD (p = 0.001), Tp-Te interval (p = 0.001), Tp-Te dispersion (p < 0.0001), and Tp-Te/QT ratio (p = 0.01) compared to those with angina preceding their incident infarction (PIA). This was reflected into significantly higher rates of in-hospital arrhythmias among patients with no PIA (20% vs. 7%, p = 0.04). Furthermore, longer Tp-Te interval and higher Tp-Te/QT ratio independently predicted in-hospital ventricular arrhythmias. CONCLUSION: Pre-infarction angina patients had better electrocardiographic measures of repolarization dispersion and encountered significantly less arrhythmic events compared to patients who did not experience PIA.

Validity of tortuosity severity index in chest pain patients with abnormal exercise test and normal coronary angiography.

BACKGROUND: Coronary tortuosity (CT) had different definitions and scores in literature with unclear pathophysiological impact. OBJECTIVES: To study degree of CT and it's relation to ischemic changes in patients with angina but normal coronary angiography (CA). METHODS: We conducted a prospective study at University hospitals between May 2016 and January 2017. We included 200 consecutive patients who underwent CA due to chest pain assumed to be of cardiac origin, and their CA was normal (no diameter stenosis >30%, nor myocardial bridging). Patients were prospectively divided into 2 groups based on the presence (n = 113) or absence (n = 87) of ischemic changes during stress study and compared for clinical, echocardiographic and CA characteristics. A newly proposed Tortuosity Severity Index (TSI) was developed into significant (mild/moderate CT with more than 4 curvatures in total, or severe/extreme CT with any number of curvatures) or not significant TSI (mild CT with curvatures less than or equal to 4 curvatures in total). RESULTS: Patients with ischemic changes had the highest rate of CT (76.5 vs 18%, p = 0.004) compared to those without. CT mostly affects the left anterior descending (LAD) coronary artery in mid and distal segments. Females, elderly, and hypertensives with left ventricular hypertrophy were strongly related to CT. Multivariate logistic regression analysis identified CT with significant TSI as the only predictor of ischemic changes in these patients (OR = 6.2, CI = 2.5-15.3, P = <0.001). CONCLUSIONS: Coronary tortuosity is a strong predictor of anginal pain among patients with normal CA, despite positive stress study. This finding is more pronounced among elderly, hypertensive female patients.

Demographic features and prevalence of myocarditis in patients undergoing transarterial endomyocardial biopsy for unexplained cardiomyopathy.

BACKGROUND: The diagnosis of myocarditis is still a challenge. The true incidence of the disease is unknown due to great variation in clinical manifestations. OBJECTIVE: The aim of this study was to identify the demographic features and in-hospital prevalence of myocarditis in patients undergoing transarterial endomyocardial biopsy (EMB) for unexplained cardiomyopathy. PATIENTS AND METHODS: This was a prospective observational study. We recruited all patients with unexplained cardiomyopathy presented at Assiut University Hospital from January 2014 till December 2014. The inclusion criteria were namely acute symptoms of heart failure, worsening of ejection fraction (EF) despite optimized therapy, hemodynamically significant arrhythmias, heart failure with concurrent rash, fever, or peripheral eosinophilia and new-onset cardiomyopathy in the presence of known amyloidosis. We excluded patients with uncontrolled hypertension, diabetes mellitus, ischemic, congenital, rheumatic heart disease, peripartum cardiomyopathy, cardiotoxic exposure, alcoholic and familial cardiomyopathies. All patients were subjected to full examination with ECG, echocardiography and coronary angiography, and then 3 EMB samples via femoral artery were taken from the LV. The histopathological examination of all biopsies was done. RESULTS: Out of the 1100 patients admitted to our department, 15 patients (1.4%), who had unexplained cardiomyopathy were included in our study. Seventy-three percent were males with mean age 37.8 ± 17 y. 87% were from rural areas, and 73.3% presented with dyspnea grade III to IV for a duration period that varied from 2 to 8 weeks. 33% had an EF > 40%. 33 EMB samples from 11 patients were examined. 7 out of 11 patients (63.6%) proved to have myocarditis on pathological examination, 5 of them had active myocarditis, 1 had chronic myocarditis and 1 had borderline myocarditis. Three patients (27.3%) had no pathological evidence of inflammation and one patient (9.1%) had cardiac amyloidosis. Four out of 15 patients (26.7%) did not undergo EMB because of LV thrombus or bleeding tendency. None of our patients had any complication from EMB. CONCLUSION: The in-hospital prevalence of myocarditis is high among patients with unexplained cardiomyopathy. EMB via femoral artery is safe and essential in confirming the diagnosis.

Cardioprotective effect of atorvastatin alone or in combination with remote ischemic preconditioning on the biochemical changes induced by ischemic/reperfusion injury in a mutual prospective study with a clinical and experimental animal arm.

BACKGROUND: Atorvastatin and remote ischemic preconditioning (RIPC) have beneficial cardiovascular protective effects. The aim of the study was to investigate possible effect of this drug alone and in combination with RIPC on the biochemical changes induced by ischemic/reperfusion injury (I/R) in a combined study with a clinical and experimental animal arm. METHODS: Thirty consecutive patients undergoing elective percutaneous coronary intervention (PCI) were divided into three groups (10 each): group I (control group without any preconditioning), group II (patients who were maintained on atorvastatin (80mg/day) for one month before PCI), and group III (similar to group II but PCI was preceded by RIPC). On the other hand, sixty adult male New Zealand white rabbits were divided into 6 groups (10 each): group I (control), group II (sham), group III (I/R as 30min ischemia followed by 120min reperfusion), group IV (regular atorvastatin 10mg/kg for 40days orally followed by I/R), group V (I/R preceded by RIPC) and group VI (similar to group IV but I/R was preceded by RIPC). Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), troponin I (cTnI), creatine kinase MB (CK-MB) and C-reactive protein (CRP) were measured in blood for all study groups. RESULTS: Clinical and experimental parts showed that groups with RIPC combined with atorvastatin pre-treatment showed a synergistic protective effect against I/R injury as evidenced by significant reduction (P<0.001) in the levels of TNF-α, cTnI (in patients) and IL-6, CK-MB and CRP (in rabbits) while the level of NO was significantly (P<0.001) increased compared with other groups. CONCLUSIONS: Pretreatment with atorvastatin combined with RIPC can exert a synergistic cardioprotective effects by reducing the possible biochemical changes related to ischemic reperfusion injury.

Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate.

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.

Factors influencing warfarin response in hospitalized patients.

The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range. Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8 mg ± 0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p = .034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72-0.94]), being a male patient (OR, 2.86 [95% CI, 1.05-7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07-0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28-10.9]). Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered.

Can exercise capacity assessed by the 6 minute walk test predict the development of major adverse cardiac events in patients with STEMI after fibrinolysis?

BACKGROUND: To assess the added value of the 6 minute walk test distance (6MWTD) in the risk-stratification methods for patients with ST -segment elevation myocardial infarction (STEMI) treated with fibrinolysis. METHODOLOGY/PRINCIPAL FINDINGS: This is a prospective cohort study of one hundred consecutive patients with STEMI, who had received fibrinolysis, at Assuit University Hospital. All patients underwent 6MWT pre- discharge and were followed up for 3 months to monitor the incidence of major adverse cardiac events (MACE). Patients were divided into 3 groups according to the level of 6MWTD (level I>450 m, level II = 300-450 m and level III<300 m). Among the study population, the median 6MWT distance was 370 meters (interquartile range 162-462). The mean age was 60.9±10.7 years, 71.9% of them were males, 2/3 had anterior MI. only 10.5% had successful thrombolysis. Compared to patients in level I (>450 m), patients in level III (<300 m) were more likely to have clinical risk factors as hypertension, diabetes and impaired renal function. The patient's mean TIMI score was 3.4±2.2, the mean GRACE score was 150.5±27.7. There was a significant negative correlation between the 6 MWTD and GRACE risk score (r = -0.80, p<0.001). At 3 months of follow-up, 51% had MACE including 16% were dead. Multivariate logistic regression analysis identified that the GRACE risk score and 6MWT distance levels were the best predictors of the MACE at 3 month of follow up. The incidence of MACE was 4 times higher in patients with high GRACE risk score who couldn't walk more than 300 meters (OR = 4.66, 95% CI = 1.1-14.5, p = 0.006). CONCLUSIONS/SIGNIFICANCE: In patients with STEMI treated with fibrinolysis, the addition of 6MWTD assessment pre-discharge to the traditional GRACE risk score improved the risk prediction of cardiovascular events at 3 month follow up.

Late stent malapposition risk is higher after drug-eluting stent compared with bare-metal stent implantation and associates with late stent thrombosis.

AIMS: Late stent malapposition (LSM) may be acquired (LASM) or persistent. LSM may play a role in patients who develop late stent thrombosis (ST). Our objective was to compare the risk of LASM in bare metal stents (BMS) with drug-eluting stents (DES) and to investigate the possible association of both acquired and persistent LSM with (very) late ST. METHODS AND RESULTS: We searched PubMed and relevant sources from January 2002 to December 2007. Inclusion criteria were: (a) intra-vascular ultrasonography (IVUS) at both post-stent implantation and follow-up; (b) 6-9-month-follow-up IVUS; (c) implantation of either BMS or the following DES: sirolimus, paclitaxel, everolimus, or zotarolimus; and (d) follow-up for LSM. Of 33 articles retrieved for detailed evaluation, 17 met the inclusion criteria. The risk of LASM in patients with DES was four times higher compared with BMS (OR = 4.36, CI 95% 1.74-10.94) in randomized clinical trials. The risk of (very) late ST in patients with LSM (five studies) was higher compared with those without LSM (OR = 6.51, CI 95% 1.34-34.91). CONCLUSION: In our meta-analysis, the risk of LASM is strongly increased after DES implantation compared with BMS. Furthermore, LSM seems to be associated with late and very late ST.