The Changes of Vasoactive Substances Originated Endotheiium in Patients with Unstable Angina Pectoris Treated by Improved Thrombolytic Therapy

Unstable angina pectoris (UAP) is one of the se-vere and potentially dangerous situations of acute coro- nary artery syndrome and may develop to acute myocar- dial infarction (AMI) or sudden death. Some drugs in- cluding low molecular weight heparin sometimes can not get satisfied effects. Obvious effects can be a- chieved by large dose of urokinase, but side effects are clear too. Sometimes, it is difficult to use large dose clinically. In this study, 120 patients with UAP hospi- talized …     

Comparison of Results of Coronary Angioplasty in Patients with Unstable vs. Stable Angina

Objectives To compare the short and mid - term outcomes in cases of percutaneous transluminal coronary angioplasty (PTCA) in patients with unstable v stable angina. Methods Patients selected for PTCA/stenting were divided in to two groups, one with stable angina pectoris (SA group, n = 92) and one with unstable angina pectoris (UA group, n = 112). The outcomes of coronary an giographies (CAG), initial (30-d) success of the procedure, and follow - up status in the two groups were compared. Results Baseline characteristics were similar, although the patients with unstable symptoms more females ( P< 0. 05), and had a higher average CCS class (P< 0. 05) and a higher incidence of postinfarction angina ( P< 0. 01). The frequency of ' complex stenosis in patients with unstable angina was higher than that of patients with stable angina, 33% v 20% ( P< 0. 01). A total of 309 vessels ac cepted the procedure; including 210 stents were sue cessfully delivered to 156 patients. 143 and 67 stents were implanted in the     

Is Cardiac Catheterization Necessary in the Era of Echocardiography?

Definitive evaluation of cardiovascular disease is traditionally accomplished by cardiac catheterization. Advances in transthoracic and transesophageal Doppler echocardiography provides an accurate and cost-effective approach when compared to cardiac catheterization. Recent data suggests that for most adult patients with aortic or mitral valve disease, Doppler echocardiographic data enables the clinician to make the same decision reached with catheterization data. Echo and Doppler studies are useful in guiding certain therapeutic interventional procedures, and in the diagnosis of aortic dissection, mechanical complications of myocardial infarction, and in identifying aortic atheromas as a potential source of embolism. Future research will need to demonstrate that not only is echocardiography cost-effective, but that it will change the outcome of the patient.     

“Hot” Unstable Angina—Is it Worse than Subacute Unstable Angina? Results from the GUARANTEE Registry

Abstract. Background and Methods: Because time to presentation to the hospital affects time to treatment and is known to be important in acute myocardial infarction, we evaluated this variable in patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). Among 2909 consecutive patients with UA/NSTEMI admitted to 35 hospitals in 6 geographic regions of the United States, we compared patients with acute (onset of pain <12 hours before admission) and subacute (onset >12 hours) unstable angina. Results: Patients with hot (acute) unstable angina presented more often to the emergency department and were subsequently admitted more often to an intensive care unit. Hospital administration of medications did not differ between the two groups, with the exception of heparin, which was paradoxically used more often in subacute patients (p<0.001). All cardiac invasive procedures were undertaken less often in the acute patients (catheterization, 41.4% vs. 58.7%, p=0.001; percutaneous coronary intervention, 11.3% vs. 21.1%, p=0.001; coronary artery bypass grafting, 5.6% vs. 12.0%, p=0.001). A greater percentage of acute patients were found to have no significant coronary artery disease at cardiac catheterization (20.1% vs. 15.0%, p=0.006). Mortality did not differ between the two groups; however, the composite endpoint of death and MI favored the acute patients (1.3% vs. 2.2%, p=0.032). Conclusions: Contrary to our initial hypothesis, hot UA patients tended to be at lower risk than patients with subacute presentation, highlighting the fact that patients with UA/NSTEMI remain at high risk even after the initial 12-hour period.     

Angina: Who Needs It? Cardioprotection in the Preconditioning Era

Over the past two decades, it has been demonstrated in various animal species that the myocardium possesses innate adaptive mechanisms that may render it more resistant to ischemic injury. Ischemic preconditioning, defined as the protection conferred to ischemic myocardium by prior episodes of brief sublethal ischemia, is one of the most potent of such adaptive phenomena. Extensive research over the past decade has alluded to the cellular mechanisms underlying this powerful means of reducing myocardial ischemia-reperfusion injury. Moreover, the possibility that such adaptive mechanisms might be inducible in the human heart has generated considerable excitement and enthusiastic research, which has significantly enhanced our understanding of the pathogenesis of ischemia-reperfusion injury. An insight into the mechanisms underlying the cardioprotective properties of ischemic preconditioning has, on the one hand, directed research aimed at identification of novel therapeutic agents for the treatment of ischemic heart disease, and on the other, questioned the use of potentially deleterious agents that may abolish the cardioprotective actions of ischemic preconditioning in patients with angina. Current studies are under way to evaluate the potential protection afforded by these preconditioning agents in patients with acute coronary syndromes, and some early reports provide some basis for optimism that a beneficial and clinically detectable improvement in myocardial protection may be possible. This article reviews our current knowledge of the cellular mechanisms responsible for mediation of ischemic preconditioning, the evidence for the existence of this phenomenon in humans, and its potential therapeutic applications.     

The Study of hemodynamics and coronary arteriography of Patients with Different Types of Unstable Angina Pectoris

Objectives To explore the basic heart functional state and cardiac reserve function of patients with different types of unstable angina pectoris (UAP) and observe the relations between the heart function and severity of coronary arterial disease. Methods 70 cases with UAP were enrolled including 25 patients with angina decubitus (AD), 23 patients with mixed angina (MA) , and 22 patients with accelerated effort angina (AEA). All patients underwent a series of examination such as UCG, ECT, hemodynamics and volume-loading test. The patients were divided into three groups in light of the results of the hemodynamic examination: ① diastolic dysfunction group ② systolic dysfunction group ③ normal heart function group. We assessed the basic heart function and cardiac reserve function of patients with different types of UAP and also observed the relations between coronary arteriography and heart function. Results ① Under basic conditions, patients with angina decubitus suffered from the systolic (36%) or dia     

Effect of Glycoprotein IIb/IIIa Inhibitors on the Individual Components of Composite Endpoints Used in Clinical Trials of Unstable Angina and Non–Q-Wave Myocardial Infarction

Inhibitors of the platelet glycoprotein (GP) IIb/IIIa receptor complex have recently been approved for the treatment of patients with unstable angina and non–Q-wave myocardial infarction (MI). We performed a meta-analysis to ascertain the effect of these agents on the individual endpoints of death, myocardial infarction, refractory ischemia, and major bleeding after 30 days of follow-up. Five randomized, placebo-controlled trials involving 17,255 patients were identified. The odds ratios for each of the endpoints in each trial were calculated and combined using a fixed-effects model. There was no significant reduction in death (OR, 0.87; 95% CI, 0.73–1.03; P = 0.1), myocardial infarction (OR, 0.91; 95% CI, 0.82–1.004; P = 0.06), or refractory ischemia (OR, 0.92; 95% CI, 0.78–1.1; P = 0.36) in patients treated with GP IIb/IIIa inhibitors. There was a significant increase in major bleeding following treatment with GP IIb/IIIa inhibitors (OR, 1.2; 95% CI, 1.06–1.4; P = 0.005). When used to treat unstable angina and non–Q-wave MI, this new class of agents appears to be associated with minimal clinical benefit and an increase in major bleeding complications.     

Circulating Levels of IL-1β, a Prothrombotic Cytokine,are Elevated in Unstable Angina Versus Stable Angina

Background: Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. However, of the known proinflammatory cytokines, only elevated plasma levels of interleukin-6 have been linked to unstable angina. We sought to examine the plasma levels of other major proinflammatory cytokines in similar clinical settings and to determine the extent of the relationship between inflammation and unstable coronary syndromes by measuring the levels of various proinflammatory cytokines in patients with stable and unstable angina.Methods: We measured plasma levels of interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), and interleukin 6 (IL-6) in 97 patients: 67 with stable angina, 24 with unstable angina, and 15 healthy controls.Results: Mean levels of IL-1 were significantly higher in patients with unstable angina as compared to patients with stable angina (p = .009). Levels of IL-6 were significantly higher than control patients for both stable angina and unstable angina patients (p = .031 and .006, respectively). No significant differences were found in the levels of TNF-.Conclusions: Our results suggest that both IL-1 and IL-6 contribute to the pathogenesis of unstable angina, and that the profile of circulating plasma levels of proinflammatory cytokines differs in unstable angina from that in stable angina.Abbreviated Abstract. Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. We measured plasma levels of interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), and interleukin 6 (IL-6) in patients with stable and unstable coronary syndromes. Levels of IL-1 and IL-6 were found to be elevated in patients with unstable coronary syndromes. No significant differences were found in the levels of TNF-. Our results suggest that both IL-1 and IL-6 contribute to the pathogenesis of unstable angina.     

Evaluation of Clinical Innovation: A Gray Zone in the Ethics of Modern Clinical Practice?

BACKGROUND

Various stakeholders can have differing opinions regarding ethical review when introducing new procedures with patients.

OBJECTIVE

This pilot study examines the way in which Research Ethics Boards (REBs; Institutional Review Boards) and clinical biochemists (CBs; laboratory medicine specialists) differ in their interpretation of what is research and what should be considered common practice versus innovation versus experimentation when introducing new procedures with patients. It also explores whether these groups agree on who is responsible for the ethical review of new procedures.

METHODS

A validated case scenario for the introduction of a new diagnostic test into clinical practice was sent to CBs and REBs across Canada. Participants were asked to determine whether the scenario constituted research; whether the test procedure should be considered as experimental, innovative, or commonly accepted care; and whether the project required approval by a REB and, if not, who should be responsible for ethical review.

RESULTS

Results showed 81% of 37 CBs and 52% of 27 REBs identified the scenario as research. Responsibility for ethical review was assigned to REBs by 44% of REBs and 54% of CBs. Of all participants, 53% classified the test procedure as ‘innovative’, 8% as ‘experimental’, whereas 17% classified it as ‘commonly accepted’.

CONCLUSIONS

This pilot study indicates a substantial variation in the ethical assessment of innovation in clinical care. This suggests the need to further elaborate on the types of innovation in health care and categorize the nature of the risks associated with each.

     

The Clinical Utility of Plasma Epstein–Barr Virus DNA Assays in Nasopharyngeal Carcinoma: The Dawn of a New Era?: A Systematic Review and Meta-Analysis of 7836 Cases

In this study, we assessed the potential of plasma Epstein–Barr virus (EBV) DNA assays to predict clinical outcomes in a large sample of nasopharyngeal carcinoma (NPC) patients and proposed a risk stratification model based on standardized EBV DNA load monitoring.We conducted a meta-analysis of 14 prospective and retrospective comparative studies (n = 7 836 patients) to evaluate the correlation between pretreatment plasma EBV DNA (pre-DNA), midtreatment plasma EBV DNA (mid-DNA), posttreatment plasma EBV DNA (post-DNA), the half-life value of plasma EBV DNA clearance rate (t_1/2), and clinical outcomes. Our primary endpoint was overall survival (OS). Our secondary endpoints were progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS).High pre-DNA, detectable mid-DNA, detectable post-DNA, and slow EBV DNA clearance rates were all significantly associated with poorer OS, with hazard radios (HRs) equal to 2.81, 3.29, 4.26, and 3.58, respectively. Pre-DNA, mid-DNA, and post-DNA had the same effects on PFS, DMFS, and LRFS.Plasma EBV DNA assays are highly prognostic of long-term survival and distant metastasis in NPC patients. Based on the results of this meta-analysis, we propose a 4-grade systematic risk stratification model. Given the inherent limitations of the included studies, future well-designed randomized clinical trials are required to confirm to the findings of this analysis and to contribute to the development of individualized treatment strategies for NPC patients.     

B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin for Risk Stratification in Low-Flow,Low-Gradient Aortic Stenosis: A Substudy of the TOPAS Study

Objectives

The objective of this study was to determine the prognostic value of combined measures of B-type natriuretic peptide (BNP) and high-sensitivity cardiac troponin T (hsTnT) in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) who had either a preserved or reduced left ventricular ejection fraction (LVEF).

Non–AIDS-Defining Malignancies in Patients with HIV in the HAART Era

The introduction of highly active antiretroviral therapy (HAART) has drastically changed the scope and spectrum of diseases associated with HIV, shifting from AIDS-related to non–AIDS-related diseases. Studies linking HIV/AIDS databases to cancer registries have shown a dramatic decrease in AIDS-related malignancies and a steady increase in non–AIDS-defining malignancies (NADM). We review the causes underlying the rise in incidence of NADM and the clinical presentation, pathology, and treatment outcomes of the four most commonly encountered NADM in the HAART era. Meta-analysis of published studies show an increase in NADM over the general population, mostly among infection-related cancers such as anal cancer, Hodgkin lymphoma, and liver cancer. Among the non-infection-related cancers, lung and skin cancers predominate. The overall effect of HAART on NADM is unsettled. As HIV-infected individuals survive longer, better screening strategies are needed to detect cancer earlier, and prospective data are needed to assess the impact of HAART on cancer outcomes.     

Cardiac Drug Therapy—Considerations in the Elderly

Elderly individuals constitute a majority of patients encountered in current cardiovascular clinical practice. Management of these patients is a clinical challenge owing to a multitude of factors. Although medications such as statins have been shown to reduce cardiovascular mortality in the general population, evidence supporting the use of these drugs in patients greater than 75 years of age is sparse. Furthermore, aging associated changes in organ function and associated comorbidities influence the pharmacokinetics of multiple medications and can potentiate drug toxicity. In this article, we review the evidence behind the use of common cardiovascular medications in elderly patients and discuss pertinent clinical challenges.     

Quality of Life in Patients with Cirrhosis—Measurement and Clinical Impact

Purpose of the Review

As understanding of liver disease progression to cirrhosis has expanded, there has also been an acceleration in clinical trials and treatment options for the different underlying causes of cirrhosis to include chronic viral hepatitis, alcoholic and non-alcoholic fatty liver disease. It is imperative that healthcare practitioners fully appreciate the impact of liver disease and treatment from the patients’ and society perspective.

Recent Findings

An important aspect of patient-reported outcomes (PROs) is assessment of health-related quality of life (HRQL) completed using generic or disease-specific instruments. In the past decades, substantial evidence has been complied that demonstrates development of cirrhosis which has a significant negative impact on a patients’ HRQL while effective treatment leads to significant gains in HRQL especially for patients with decompensated cirrhosis.

Summary

Clinicians and clinical investigators must understand the importance of PROs for inclusion in clinical trials to fully assess the impact of cirrhosis on patients and the society.

     

Cell Transplantation—A Potential Therapy for Cardiac Repair in the Future?

Adult human myocardium lacks the possibility of regeneration because cardiac muscle cells do not reenter the cell cycle. Transplantation of myoblasts, cardiomyocytes, and stem-cell-derived cardiomyocytes has been done in experimental settings to replace lost myocardial tissue. This paper reviews the experimental data about cell transfer into myocardium and highlights the advantages of the particular cell types used. Transplantation of myoblast would enable an autologous transfer. They can be easily obtained and expanded in culture. Gene transfer is possible, and there exist no ethical reservations against a myoblast transfer. However, their integration in the heart tissue and final differentiation is not clear yet. Fetal cardiomyocytes are integrated in the myocardial tissue, improve cardiac function, and can be expanded in culture. However, their transfer would be allogenic, making immunosuppression necessary. Stem-cell-derived cardiomyocytes could be used to replace all three types of cardiac muscle cells. They can be expanded in culture. The possibility of teratoma formation makes a 100% selection mandatory. At present, there exist ethical concerns against working with human embryonic stem cells. Cell transfer therapy has been shown to improve myocardial function in animal experiments. This indicates that a reduced myocardial function could be improved by a cell transfer therapy. Especially stem cell-derived cardiomyocytes would allow for selective replacement of pacemaker cells or atrial or ventricular cardiomyocytes.     

Bleeding Complications and INR Control of Combined Warfarin and Low-Dose Aspirin Therapy in Patients with Unstable Angina and Non–Q-Wave Myocardial Infarction

The purpose of this study was to compare bleeding complications in patients with non–Q-wave myocardial infarction and unstable angina receiving combination therapy with aspirin plus warfarin versus aspirin alone. A post–hoc analysis was performed on patients enrolled in the Antithrombotic Therapy in Acute Coronary Syndrome (ACTACS) study, which was a prospective, randomized, multicenter trial of antithrombotic therapy in unstable angina or non–Q-wave myocardial infarction. A total of 358 patients admitted within 48 hours of chest pain were randomized to antithrombotic therapy with either (1) aspirin alone or (2) aspirin (162.5 mg) plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Major and minor bleeding episodes, hemoglobin levels, and prothrombin times or INR levels were prospectively recorded. Major bleeding episodes were subclassified as relating to CABG/PTCA or not. The rate of major bleeding complications not associated with CABG or PTCA was 2.0%, and did not differ between therapy assignments. Among 55 patients undergoing CABG, 29 (53%) required transfusion of two or more units of blood. Minor bleeding was also infrequent (2.8%). All patients with minor bleeding had a full clinical recovery, and only one patient with a major bleed resulted in minor disability. Warfarin was well managed, with 50% of INRs falling between 1.9 and 2.7. Combination therapy with low-dose aspirin and warfarin (INR mean 2.5) produces an insignificant rise in the incidence of major and minor bleeding. These events are infrequent and do not usually result in major disability. The effect of longer duration combination therapy remains to be determined.     

The Effect of Weight Loss on Clinical Outcomes in Patients Implanted With a Cardiac Resynchronization Therapy Device—A MADIT-CRT Substudy

BackgroundThere are no data regarding the effect of weight loss on clinical outcomes in patients undergoing cardiac resynchronization therapy. This study was designed to evaluate the effect of weight loss on clinical outcomes in patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D).Methods and ResultsThe risk of heart failure (HF) or death, and of death alone, was compared between patients with and without weight loss of ≥2 kg or more at 1 year in the CRT-D arm of the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT). Weight loss was observed in 170 of 994 patients (17%) implanted with a CRT-D. Multivariate analysis showed a significant increase in the risk of HF or death among patients with weight loss compared with those without weight loss (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.26–2.63; P = .001). Weight loss was associated with a 79% increase in the risk of all-cause mortality (HR 1.79, 95% CI 1.16–3.34; P = .01). When analyzed in a continuous fashion, each kg of weight loss was associated with a 4% increase in the risk of HF or death (P = .03). In left bundle branch block (LBBB) patients with a CRT-D, weight loss was associated with an especially high risk of HF or death (HR 2.23, 95% CI 1.36–3.65; P = .002) and of death alone (HR 2.33, 95% CI 1.07–5.06; P = .03; interaction P = .26).ConclusionsIn patients with mild symptoms of HF receiving CRT-D, weight loss observed at 1 year is associated with adverse clinical outcomes, especially in those with a LBBB electrocardiographic pattern.