Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating d-Galactosamine induced fulminant hepatic failure in Wistar rats.

Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against d-Galactosamine (d-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of d-GalN (700mg/kgBW). Genistein (5mg/kgBW/day) was given as pre-treatment for 30days via intra-gastric route followed by d-GalN (700mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of d-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/ß and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in d-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell.

Relationship between angina pectoris and outcomes in patients with heart failure and reduced ejection fraction: an analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

AIM: Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). METHODS AND RESULTS: Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan-Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54-3.61; P < 0.001), this composite plus coronary revascularization (HR: 2.54, 1.76-3.68; P < 0.001), as well as HF hospitalization (HR: 1.35, 1.13-1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization. CONCLUSION: Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.

EEG seizure detection: concepts, techniques, challenges, and future trends.

A central nervous system disorder is usually referred to as epilepsy. In epilepsy brain activity becomes abnormal, leading to times of abnormal behavior or seizures, and at times loss of awareness. Consequently, epilepsy patients face problems in daily life due to precautions they must take to adapt to this condition, particularly when they use heavy equipment, e.g., vehicle derivation. Epilepsy studies rely primarily on electroencephalography (EEG) signals to evaluate brain activity during seizures. It is troublesome and time-consuming to manually decide the location of seizures in EEG signals. The automatic detection framework is one of the principal tools to help doctors and patients take appropriate precautions. This paper reviews the epilepsy mentality disorder and the types of seizure, preprocessing operations that are performed on EEG data, a generally extracted feature from the signal, and a detailed view on classification procedures used in this problem and provide insights on the difficulties and future research directions in this innovative theme. Therefore, this paper presents a review of work on recent methods for the epileptic seizure process along with providing perspectives and concepts to researchers to present an automated EEG-based epileptic seizure detection system using IoT and machine learning classifiers for remote patient monitoring in the context of smart healthcare systems. Finally, challenges and open research points in EEG seizure detection are investigated.

The Impact of COVID-19 on Preterm Birth Among Pregnant Women in Al-Qassim, Saudi Arabia.

BACKGROUND: Pregnant women are regarded as a unique group due to the distinct immunological condition that pregnancy produces, which makes pregnant women more susceptible to respiratory infections like coronavirus disease 2019 (COVID-19) and its consequences. During pregnancy, many viral infections have been recognized to increase the risk of adverse obstetrical outcomes such as preterm delivery. The purpose of this study was to investigate the effects of COVID-19 infection on preterm birth in pregnant women in the Al-Qassim region of Saudi Arabia. METHODS:  This retrospective cohort study was conducted in Saudi Arabia between December 2019 to October 2021. The target subjects were pregnant women with live singleton gestations who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing for COVID-19 infection during their delivery hospitalization. Data gathered included patient demographic information, clinical characteristics, and pregnancy outcomes. Data were analyzed using R version 4.1.1 (R Core Team (2021); R Foundation for Statistical Computing, Vienna, Austria). RESULTS:  A total of 381 pregnant women were included. The median maternal age of women was 31.0 years (IQR: 27.0, 35.0) and the median BMI value was 30.5 kg/m2 (IQR: 26.9, 34.8). The most common comorbidities were diabetes (7.1%) and asthma (4.5%). A known history of preterm birth was prevalent among 2.9%. Of the participants, 13.6% had a prenatal COVID-19 infection, of whom 57.7% had their infections resolved. The prevalence of positive PCR testing was 13.6%. Preterm birth occurred in 46 women (12.1%, 95%CI 9.1-15.9). Preterm birth was significantly associated with having a maternal age of ≥35 years, having high frequencies of parity, and having a past history of preterm birth, as well as having a history of hypertension and diabetes. Preterm birth was not significantly associated with having a confirmed COVID-19 infection at delivery. CONCLUSION: It was shown that preterm birth is evident among women with COVID-19 infection. Preterm birth is significantly associated with old age, multiparity, and a history of preterm delivery. Preterm birth is not significantly associated with having a confirmed COVID-19 infection at delivery. More research regarding infection-related adverse effects is advised and should be highlighted.

Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.

Background: Molecular analyses in hematological malignancies provide insights about genetic makeup. Probable etiological factors in leukemogenesis could also be disclosed. Since genetic analyses are still primitive in Iraq, a country of repeated wars, we conceived of performing next-generation sequencing (NGS), to disclose the genomic landscape of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among a cohort of Iraqi children. Methods: Dried blood samples were collected from Iraqi children with ALL (n=55), or AML (n=11), and transferred to Japan where NGS was done. Whole-exome, whole-genome, and targeted gene sequencings were performed. Results: Somatic point mutations and the copy number variations among Iraqi children with acute leukemia were comparable with those in other countries, and cytosine-to-thymine nucleotide alterations were dominant. Strikingly, TCF3-PBX1 was the most recurrent fusion gene (22.4%) in B-cell precursor ALL (B-ALL), and acute promyelocytic leukemia (AML-M3) was subtyped in 5 AML cases. Additionally, a high frequency of RAS signaling pathway mutations was detected in children with B-ALL (38.8%), along with 3 AML cases that carried oncogenic RAS. Conclusions: Apart from disclosing the high frequency of TCF3-PBX1, NGS confirmed our previous finding of recurrent RAS mutations in Iraqi childhood acute leukemia. Our results suggest that the biology of Iraqi childhood acute leukemia is in part characteristic, where the war-aftermath environment or geography might play a role.

Recent Advances and Therapeutic Journey of Schiff Base Complexes with Selected Metals (Pt, Pd, Ag, Au) as Potent Anticancer Agents: A Review.

Schiff bases and their transition metal complexes play an important role in the field of medicine, in particular in the treatment of cancer. Since the discovery of the cisplatin anticancer activity, great efforts have focused on the rational design of metal-based anticancer drugs that can be potentially used for the treatment of cancer. However, drug resistance and significant side effects greatly limit its clinical application. This has inspired medicinal chemists to employ various strategies in the development of novel and effective anticancer drugs. Recently, a greater number of transition metal complexes have been designed and evaluated for their anticancer activities, and some of them were at different stages of clinical studies. Amongst these, platinum, palladium, gold and silver complexes have an important place within medicinal and inorganic chemistry. This review article discusses Schiff bases and their complexes with selected transition metals (Pd, Pt, Ag, Au) for anticancer activity against different cancer cell lines.

Antifungal activity of α-methyl trans cinnamaldehyde, its ligand and metal complexes: promising growth and ergosterol inhibitors.

Antifungal effectivity and utility of cinnamaldehyde is limited because of its high MIC and skin sensitivity. In this study, α-methyl trans cinnamaldehyde, a less irritating derivative, have been self coupled and complexed with Co(II) and Ni(II) to generate N, N'-Bis (α-methyl trans cinnamadehyde) ethylenediimine [C(22)H(24)N(2)], [Co(C(44)H(48)N(4))Cl(2)] and [Ni(C(44)H(48)N(4))Cl(2)]. Ligand and complexes were characterized on the basis of FTIR, ESI-MS, IR and (1)HNMR techniques. Synthesized ligand [L] and complexes were investigated for their MICs, inhibition of ergosterol biosynthesis and H(+) extrusion against three strains of Candida: C. albicans 44829, C. tropicalis 750 and C. krusei 6258. Average of three species MIC of methyl cinnamaldehyde is 317 µg/ml (2168 µM). Compared to methyl cinnamaldehyde ligand [L], Co(II) and Ni(II) complex are found to be 4.48, 17.78 and 21.46 times more effective in liquid medium and 2.73, 8.93 and 10.38 times more effective in solid medium. At their respective MIC(90) average inhibition of ergosterol biosynthesis caused by methyl cinnamaldehyde, ligand [L], Co(II) and Ni(II) complex, respectively was 80, 78, 90 and 93%. H(+) extrusion was also significantly inhibited but did not co-relate well with MIC(90). Results indicate ergosterol biosynthesis as site of action of α-methyl cinnamaldehyde, synthesized ligand and complexes. α-methyl cinnamaldehyde and ligand did not show any toxicity against H9c2 rat cardiac myoblast cell, whereas Co(II) and Ni(II) complexes on an average produced 19% cellular toxicity.

Automated seizure diagnosis system based on feature extraction and channel selection using EEG signals.

Seizure is an abnormal electrical activity of the brain. Neurologists can diagnose the seizure using several methods such as neurological examination, blood tests, computerized tomography (CT), magnetic resonance imaging (MRI) and electroencephalogram (EEG). Medical data, such as the EEG signal, usually includes a number of features and attributes that do not contains important information. This paper proposes an automatic seizure classification system based on extracting the most significant EEG features for seizure diagnosis. The proposed algorithm consists of five steps. The first step is the channel selection to minimize dimensionality by selecting the most affected channels using the variance parameter. The second step is the feature extraction to extract the most relevant features, 11 features, from the selected channels. The third step is to average the 11 features extracted from each channel. Next, the fourth step is the classification of the average features using the classification step. Finally, cross-validation and testing the proposed algorithm by dividing the dataset into training and testing sets. This paper presents a comparative study of seven classifiers. These classifiers were tested using two different methods: random case testing and continuous case testing. In the random case process, the KNN classifier had greater precision, specificity, positive predictability than the other classifiers. Still, the ensemble classifier had a higher sensitivity and a lower miss-rate (2.3%) than the other classifiers. For the continuous case test method, the ensemble classifier had higher metric parameters than the other classifiers. In addition, the ensemble classifier was able to detect all seizure cases without any mistake.

Epitope-Based Peptide Vaccine Design against Fructose Bisphosphate Aldolase of Candida glabrata: An Immunoinformatics Approach.

BACKGROUND: Candida glabrata is a human opportunistic pathogen that can cause life-threatening systemic infections. Although there are multiple effective vaccines against fungal infections and some of these vaccines are engaged in different stages of clinical trials, none of them have yet been approved by the FDA. AIM: Using immunoinformatics approach to predict the most conserved and immunogenic B- and T-cell epitopes from the fructose bisphosphate aldolase (Fba1) protein of C. glabrata. Material and Method. 13 C. glabrata fructose bisphosphate aldolase protein sequences (361 amino acids) were retrieved from NCBI and presented in several tools on the IEDB server for prediction of the most promising epitopes. Homology modeling and molecular docking were performed. RESULT: The promising B-cell epitopes were AYFKEH, VDKESLYTK, and HVDKESLYTK, while the promising peptides which have high affinity to MHC I binding were AVHEALAPI, KYFKRMAAM, QTSNGGAAY, RMAAMNQWL, and YFKEHGEPL. Two peptides, LFSSHMLDL and YIRSIAPAY, were noted to have the highest affinity to MHC class II that interact with 9 alleles. The molecular docking revealed that the epitopes QTSNGGAAY and LFSSHMLDL have the lowest binding energy to MHC molecules. CONCLUSION: The epitope-based vaccines predicted by using immunoinformatics tools have remarkable advantages over the conventional vaccines in that they are more specific, less time consuming, safe, less allergic, and more antigenic. Further in vivo and in vitro experiments are needed to prove the effectiveness of the best candidate's epitopes (QTSNGGAAY and LFSSHMLDL). To the best of our knowledge, this is the first study that has predicted B- and T-cell epitopes from the Fba1 protein by using in silico tools in order to design an effective epitope-based vaccine against C. glabrata.

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

In-situ modification of castor oil with divalent metal ions like Zn (II), Cu (II), Co (II) and Ba (II) and their comparative antioxidant study by in-vitro methods.

US Food and Drug Administration (FDA) permitted for direct addition of castor oil into food for human consumption and recently FDA approved castor oil as over-the-counter (OTC) for laxative drug. Castor oil (COL) is a vegetable oil and naturally polyol which is inexpensive, environmental friendly and a very valuable renewable resource. Metals are believed to influence antioxidant property of ligands. Metals copper, zinc, cobalt and barium were incorporated with castor oil and subsequently structures were established by FT-IR, UV-Visible, and 1H NMR spectroscopic techniques. In vitro antioxidant activities of metal containing COL were determined by DPPH and superoxide scavenging methods and the results were compared with vitamin C. Enhanced antioxidant nature of metal containing castor oil was noticed and compared to virgin castor oil. This study reveals that synthesized metal containing-COL is a potential antioxidant material.

A history of diabetes predicts outcomes following myocardial infarction: an analysis of the 28 771 patients in the High-Risk MI Database.

AIMS: To examine the impact of diabetes mellitus on long-term clinical outcomes in patients with myocardial infarction (MI) complicated by clinical signs of heart failure (HF) or left ventricular dysfunction (LVD). METHODS AND RESULTS: The High-Risk MI Database consists of individual data from 28 771 patients and was created by merging four large recent randomized clinical trials (VALIANT, EPHESUS, OPTIMAAL, and CAPRICORN) that each examined the impact of pharmacological interventions following MI in patients with evidence of HF or LVD. The mean age of patients was 65 years, 70% were male, and almost 94% Caucasian. Overall, 7368 (26%) had a history of diabetes. All the major outcomes were adjudicated by independent end-point committees. Strong and highly significant associations were found with all major clinical outcomes. Diabetes was associated with an increased risk for all-cause death [adjusted hazard ratio (HR) 1.37; confidence interval (CI) 1.28-1.46; P < 0.001]. The higher risk for all-cause death was largely mediated by higher risk for cardiovascular death (adjusted HR 1.38; CI 1.27-1.48; P < 0.001) predominantly due to a substantially increased risk for fatal re-infarction (adjusted HR 1.78; CI 1.42-2.23; P < 0.001). Additionally, diabetes was associated with an increased risk for hospitalizations, particularly HF hospitalization (adjusted HR 1.50; CI 1.39-1.63; P < 0.001). There were also elevated risks for composite outcomes, particularly death or hospitalization due to HF (adjusted HR 1.48; CI 1.38-1.59; P < 0.001). CONCLUSION: The risk for adverse outcomes associated with diabetes remains elevated even after debut of coronary artery disease in patients with MI complicated by clinical signs of HF or LVD. This association is particularly strong for HF-related outcomes.

TBX2 subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection.

The TBX2 subfamily (TBXs 2, 3, 4 and 5) transactivates or represses genes involved in lung organogenesis. Yet TBX2 subfamily expression in pathogenesis of non-small cell lung cancer (NSCLC), the most common lung malignancy, remains elusive. We sought to probe the expression profile of the TBX2 subfamily in early phases of NSCLC. Expression of TBX2 subfamily was analyzed in datasets of pan-normal specimens as well as NSCLCs and normal lung tissues. TBX2 subfamily expression in matched normal lungs, premalignant hyperplasias and NSCLCs was profiled by transcriptome sequencing. TBX2 subfamily expression was evaluated in the cancerization field consisting of matched NSCLCs and adjacent cytologically-normal airways relative to distant normal lungs and in a dataset of normal bronchial samples from smokers with indeterminate nodules suspicious for malignancy. Statistical analysis was performed using R. TBX2 subfamily expression was markedly elevated in normal lungs relative to other organ-specific normal tissues. Expression of the TBXs was significantly suppressed in NSCLCs relative to normal lungs (P < 10-9). TBX2 subfamily was significantly progressively decreased across premalignant lesions and NSCLCs relative to normal lungs (P < 10-4). The subfamily was significantly suppressed in NSCLCs and adjacent normal-appearing airways relative to distant normal lung tissues (P < 10-15). Further, suppressed TBX2 subfamily expression in normal bronchi was associated with lung cancer status (P < 10-5) in smokers. Our findings suggest that the TBX2 subfamily is notably suppressed in human NSCLC pathogenesis and may serve as a high-potential biomarker for early lung cancer detection in high-risk smokers.

Efficacy of noninvasive cardiac imaging tests in diagnosis and management of stable coronary artery disease.

The aim of this review was to discuss the current literature regarding the utility of noninvasive imaging in diagnosis and management of stable coronary artery disease (CAD) including recent data from large randomized trials assessing diagnosis and prognosis. Current guidelines recommend revascularization in patients with refractory angina and in those with potential prognostic benefit. Appropriate risk stratification through noninvasive assessment is important in ensuring patients are not exposed to unnecessary invasive coronary angiograms. The past 20 years have seen an unprecedented expansion in noninvasive imaging modalities for the assessment of stable CAD, with cardiovascular magnetic resonance and computed tomography complementing established techniques such as myocardial perfusion imaging, echocardiography and exercise electrocardiogram. In this review, we examine the current state-of-the-art in noninvasive imaging to provide an up-to-date analysis of current investigation and management options.

The collateral circulation of coronary chronic total occlusions.

AIMS: Despite advances in understanding the physiological role of collaterals in coronary chronic total occlusions (CTOs), collateral anatomy remains poorly defined. Our aim was to define the anatomy and interventional utility of collaterals within a large population of patients with CTOs. METHODS AND RESULTS: We studied the coronary angiograms of 481 patients with 519 CTOs at six centres in the U.K. over four years. Detailed angiographic analysis was performed by interventional cardiologists specialising in CTO percutaneous coronary intervention (PCI). All visible collaterals with a collateral connection (CC) grade ≥1 were recorded. A subgroup of CTOs (n=277) was assessed for interventional capability, defined as whether the collateral supply was able to facilitate retrograde access. We described 45 different collateral patterns: 20 in right coronary artery (RCA), 13 in left anterior descending (LAD), and 12 in circumflex artery CTOs. Septal collaterals from the LAD to the right posterior descending artery (RPDA), and from the posterior descending artery to the LAD were most common, and most often considered as having "interventional capability". CONCLUSIONS: This is the largest analysis of collateral circulation anatomy in a population of patients with CTOs. We anticipate that these data will be of significant benefit in angiographic analysis and procedure planning for CTO PCI.

The management of patients with aortic regurgitation and severe left ventricular dysfunction: a systematic review.

A systematic search of Medline, EMBASE and CINAHL electronic databases was performed. Original research articles reporting all-cause mortality following surgery in patients with aortic regurgitation and severe left ventricular systolic dysfunction (LVSD) were identified. Nine of the 10 eligible studies were observational, single-center, retrospective analyses. Survival ranged from 86 to 100% at 30 days; 81 to 100% at 1 year and 68 to 84% at 5 years. Three studies described an improvement in mean left ventricular ejection fraction (LVEF) following aortic valve replacement (AVR) of 5-14%; a fourth study reported an increase in mean left ventricular ejection fraction (LVEF) of 9% in patients undergoing isolated AVR but not when AVR was combined with coronary artery bypass graft and/or mitral valve surgery. Three studies demonstrated improvements in functional New York Heart Association (NYHA) class following AVR. Additional studies are needed to clarify the benefits of AVR in patients with more extreme degrees of left ventricular systolic dysfunction (LVSD) and the potential roles of cardiac transplantation and transaortic valve implantation.

Clinical Characteristics and Outcomes of Patients With Coronary Artery Disease and Angina: Analysis of the Irbesartan in Patients With Heart Failure and Preserved Systolic Function Trial.

BACKGROUND: The aim of our study was to investigate the relationship between coronary artery disease (CAD), angina, and clinical outcomes in patients with heart failure and preserved ejection fraction enrolled in the irbesartan in patients with heart failure and preserved systolic function (I-Preserve) trial. METHODS AND RESULTS: The mean follow-up period for the 4128 patients enrolled in I-Preserve was 49.5 months. Patients were divided into 4 mutually exclusive groups according to history of CAD and angina: patients with no history of CAD or angina (n=2008), patients with no history of CAD but a history of angina (n=649), patients with a history of CAD but no angina (n=468), and patients with a history of CAD and angina (n=1003); patients with no known CAD or angina were the reference group. After adjustment for other prognostic variables using Cox proportional-hazard models, patients with CAD but no angina were found to be at higher risk of all-cause mortality (hazard ratio [HR], 1.58 [1.22-2.04]; P<0.01) and sudden death (HR, 2.12 [1.33-3.39]; P<0.01), compared with patients with no CAD or angina. Patients with CAD and angina were also at higher risk of all-cause mortality (HR, 1.29 [1.05-1.59]; P=0.02) and sudden death (HR, 1.83 [1.24-2.69]; P<0.01) compared with the same reference group and had the highest risk of unstable angina or myocardial infarction (HR, 5.84 [3.43-9.95]; P<0.01). CONCLUSIONS: Patients with heart failure and preserved ejection fraction and CAD are at higher risk of all-cause mortality and sudden death when compared with those without CAD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.

Clinical characteristics and outcomes of patients with angina and heart failure in the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) Programme.

AIMS: To investigate the relationship between angina pectoris and fatal and non-fatal clinical outcomes in heart failure with reduced and preserved ejection fraction (HF-REF and HF-PEF, respectively). METHODS AND RESULTS: Of 7599 patients in the CHARM program, 5408 had ischaemic heart disease; 3855 had HF-REF (ejection fraction ≤45%) and 1553 had HF-PEF. These patients were separated into three groups: no history of angina, previous angina, and current angina. Three coronary outcomes were examined: fatal or non-fatal myocardial infarction (MI); MI or hospitalization for unstable angina (UA); and MI, UA or coronary revascularization. The composite heart failure outcome of cardiovascular death or heart failure hospitalization (HFH) was also analysed, along with its components and all-cause mortality. New York Heart Association functional class was worse in both HF-REF and HF-PEF patients with current angina compared with patients without angina (P < 0.001 and P = 0.005 respectively), despite similar clinical examination findings and ejection fraction. Patients with current angina had a higher risk of all three coronary outcomes (adjusted hazard ratios ranging from 1.8-3.1) than those without angina but did not have a higher risk of heart failure outcomes or all-cause mortality. CONCLUSION: In patients with heart failure current angina is associated with significantly more functional limitation and a higher risk of coronary events, across the spectrum of left ventricular ejection fraction.