Thrombosis and Fibrinolysis in Acute Myocardial Infarction

The development of coronary thrombosis in response to rupture of atherosclerotic plaques is the primary determinant of the evolution of stable atherosclerotic coronary disease to unstable ischemic syndromes and acute myocardial infarction. Activation of the tissue factor pathway of coagulation and adhesion of platelets are critical events in the initiation of thrombosis. However, subsequently, other factors may determine the extent of thrombosis by modulating the intensity of procoagulant and fibrinolytic activity. Marked procoagulant activity, attenuation of physiologic fibrinolytic activity, or both appear to be risk factors for myocardial infarction. The results of recent studies have provided considerable insight into potential mechanisms for thrombosis in response to rupture of atherosclerotic plaque and have identified potential novel antithrombotic interventions to inhibit the progression of coronary thrombosis.     

Coronary Recanalization Due to Presumed Thrombosis Following Surgical Ligation of a Large Right Coronary Artery to Right Ventricle Fistula

We report angiographic findings in an infant with congestive heart failure due to a large right coronary artery to right ventricular fistula who underwent surgical ligation. Repeat catheterization 2 years later unexpectedly showed extensive thrombosis of the right coronary artery with multiple recanalized channels supplying the right coronary distribution. Review of the literature showed that this may not be an uncommon finding.     

Presentation, management and outcomes of thrombosis for children with cardiomyopathy

BACKGROUND: Thrombosis in children with dilated and inflammatory cardiomyopathy is an unpredictable complication with potentially important morbidity. OBJECTIVE: To determine the prevalence, associated factors, management and outcomes of thrombosis in this setting. METHODS: Data were obtained from review of medical records. Factors associated with thrombosis and the impact on outcome were sought. RESULTS: From 1990 to 1998, 66 patients that presented with dilated cardiomyopathy were followed for a median interval of 1.4 years (range 0 to 9.79 years) from first presentation. Thrombosis was diagnosed in four patients at presentation and in four patients during follow-up. Thrombosis was noted in one additional patient at examination after death. The overall nine-year period prevalence of thrombosis was 14%. Anticoagulation was started at presentation in 31% of patients. The mean left ventricular ejection fraction at presentation was significantly lower in those given anticoagulation (19+/-8%) versus those who were not (32+/-15%; P < 0.001). The mean ejection fraction at presentation was similar in those patients with (25+/-10%) versus those without thrombosis (28+/-15%; P = 0.44). During follow-up, 11 patients died and seven underwent cardiac transplantation. Kaplan-Meier estimates of freedom from death or transplantation were 88% at three months, 81% at one year and 70% at five years. Survival free of transplantation was not affected by thrombosis. CONCLUSIONS: Thrombosis is common in children with cardiomyopathy, can occur at any time in the patients' clinical course and is not related to clinical features or survival free of transplantation. The relevance and prevention of thrombosis in this setting remains unclear.     

急性冠脉综合征患者药物洗脱支架雷帕霉素CypherTM植入后的不良反应分析

目的:分析雷帕霉素药物洗脱支架CypherTM植入后对急性冠脉综合征患者近、远期的不良反应.方法: 选择接受CypherTM治疗的冠心病患者83例,在支架植入术后9个月内全部接受门诊随访及冠脉造影,了解支架内急性和亚急性血栓、边缘效应、贴壁不良现象、支架处动脉瘤发生率及相应的不良心脏事件(MACE)发生情况.结果:83例患者共植入支架112个,植入成功率为98.8%(82/83).29例(34.9%)接受冠脉造影,MACE9例,发生率10.8%(9/83),其中,1例术中发生猝死,1例术后3d因亚急性血栓造成再发心肌梗死,其余7例在出院后1～3 月内发生心绞痛,皆经造影证实为血栓形成,再次成功靶血管血运重建8例;其余20例无症状患者造影发现支架边缘狭窄(无血栓)2例,总再狭窄为13.3%(11/83);无动脉瘤发生.9例MACE中,有弥漫病变5例,其中4例植入长支架,1例植入重叠支架,其余为简单病变;29例患者共发现贴壁不良现象5例,皆发生MACE,其中4例为弥漫病变植入长支架,1例为简单病变.结论:急性或亚急性血栓形成是药物支架CypheTM植入后出现的主要不良反应,可能与弥漫病变植入长、重叠支架引起贴壁不良有关.     

Coronary Flow Velocity Reserve during Dobutamine Stress Echocardiography

Background

A coronary flow velocity reserve (CFVR) ≥ 2 is adequate to infer a favorable prognosis or the absence of significant coronary artery disease.

Objective

To identify parameters which are relevant to obtain CFVR (adequate or inadequate) in the left anterior descending coronary artery (LAD) during dobutamine stress echocardiography (DSE).

Methods

100 patients referred for detection of myocardial ischemia by DSE were evaluated; they were instructed to discontinue the use of β-blockers 72 hours prior to the test. CFVR was calculated as a ratio of the diastolic peak velocity (cm/s) (DPV) on DSE (DPV-DSE) to baseline DPV at rest (DPV-Rest). In group I, CFVR was < 2 and, in group II, CFVR was ≥ 2. The Fisher''s exact test and Student''s t test were used for the statistical analyses. P values < 0.05 were considered statistically significant.

Results

At rest, the time (in seconds) to obtain Doppler in LAD in groups I and II was not different (53±31 vs. 45±32; p=0.23). During DSE, LAD was recorded in 92 patients. Group I patients were older (65.9±9.3 vs. 61.2±10.8 years; p=0.04), had lower ejection fraction (61±10 vs. 66±6%; p=0.005), higher DPV-Rest (36.81±08 vs. 25.63 ± 06cm/s; p<0.0001) and lower CFVR (1.67 ± 0.24 vs. 2.53 ± 0.57; p<0.0001), but no difference was observed regarding DPVDSE (61.40±16 vs. 64.23±16cm/s; p=0.42). β-blocker discontinuation was associated with a 4-fold higher chance of a CFVR < 2 (OR= 4; 95% CI [1.171-13.63], p=0.027).

Conclusion

DPV-Rest was the main parameter to determine an adequate CFVR. β-blocker discontinuation was significantly associated with inadequate CFVR. The high feasibility and the time to record the LAD corroborate the use of this methodology.     

Apixaban in Acute Coronary Syndromes

Apixaban is an orally active, selective, direct‐acting, reversible inhibitor of factor Xa that is under evaluation for the management of acute coronary syndromes (ACS). This article critically reviews the rationale and evidence for the use of anticoagulants in the long‐term management of ACS, preliminary data for apixaban from the phase 2 apixaban for prevention of acute ischemic and safety events (APPRAISE) trial, and the potential future role of apixaban for this indication.     

Cost-Effectiveness of Different Diagnostic Strategies in Suspected Stable Coronary Artery Disease in Portugal

Background

Cost-effectiveness is an increasingly important factor in the choice of a test or therapy.

Objective

To assess the cost-effectiveness of various methods routinely used for the diagnosis of stable coronary disease in Portugal.

Methods

Seven diagnostic strategies were assessed. The cost-effectiveness of each strategy was defined as the cost per correct diagnosis (inclusion or exclusion of obstructive coronary artery disease) in a symptomatic patient. The cost and effectiveness of each method were assessed using Bayesian inference and decision-making tree analyses, with the pretest likelihood of disease ranging from 10% to 90%.

Results

The cost-effectiveness of diagnostic strategies was strongly dependent on the pretest likelihood of disease. In patients with a pretest likelihood of disease of ≤50%, the diagnostic algorithms, which include cardiac computed tomography angiography, were the most cost-effective. In these patients, depending on the pretest likelihood of disease and the willingness to pay for an additional correct diagnosis, computed tomography angiography may be used as a frontline test or reserved for patients with positive/inconclusive ergometric test results or a calcium score of >0. In patients with a pretest likelihood of disease of ≥ 60%, up-front invasive coronary angiography appears to be the most cost-effective strategy.

Conclusions

Diagnostic algorithms that include cardiac computed tomography angiography are the most cost-effective in symptomatic patients with suspected stable coronary artery disease and a pretest likelihood of disease of ≤50%. In high-risk patients (pretest likelihood of disease ≥ 60%), up-front invasive coronary angiography appears to be the most cost-effective strategy. In all pretest likelihoods of disease, strategies based on ischemia appear to be more expensive and less effective compared with those based on anatomical tests.     

Percutaneous Coronary Intervention using a Full Metal Jacket with Drug-eluting Stents: Major Adverse Cardiac Events at One Year

Background

The clinical benefit of percutaneous coronary intervention (PCI) for long coronary lesions is unclear; furthermore, concerns have been raised about its safety.

Objectives

To evaluate the predictors of major adverse cardiac events (MACE) associated with PCI using a full metal jacket (FMJ), defined as overlapping drug-eluting stents (DES) measuring > 60 mm in length, for very long lesions.

Methods

We enrolled 136 consecutive patients with long coronary lesions requiring FMJ in our single-center registry. The primary endpoint included the combined occurrence of all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Demographic, clinical, angiographic, and procedural variables were evaluated using stepwise Cox regression analysis to determine independent predictors of outcome.

Results

The mean length of stent per lesion was 73.2 ± 12.3 mm and the mean reference vessel diameter was 2.9 ± 0.6 mm. Angiographic success was 96.3%. Freedom from MACE was 94.9% at 30 days and 85.3% at one year. At the one-year follow-up, the all-cause mortality rate was 3.7% (1.5% cardiac deaths), the MI rate was 3.7%, and the incidence of definite or probable stent thrombosis (ST) was 2.9%. Female gender [hazard ratio (HR), 4.40; 95% confidence interval (CI), 1.81-10.66; p = 0.001) and non-right coronary artery PCI (HR, 3.49; 95%CI, 1.42-8.59; p = 0,006) were independent predictors of MACE at one year. Freedom from adverse events at one year was higher in patients with stable angina who underwent PCI (HR, 0.33; 95%CI, 0.13-0.80; p = 0.014).

Conclusions

PCI using FMJ with DES for very long lesions was efficacious but associated with a high rate of ST at the one-year follow-up. However, the rate of cardiac mortality, nonprocedure-related MI, and MACE was relatively low. Target coronary vessel PCI, clinical presentation, and female gender are new contemporary clinical factors that appear to have adverse effects on the outcome of PCI using FMJ for long lesions.     

Renal Sympathetic Denervation for Resistant Hypertension Treatment - Current Perspectives

The authors review the concept of resistant hypertension and the involvement of the sympathetic nervous system in hypertension as a rational basis for the technique of renal sympathetic denervation (RSD) performed percutaneously. This revision is the result of an active search for scientific articles with the term "renal denervation" in the Medline and PubMed databases. The techniques and devices used in the procedure are presented, as well as clinical outcomes at six, 12 and 24 months after the intervention with the Symplicity catheter. Significant decreases and progressively higher reductions of systolic and diastolic blood pressure were observed after RSD. The complication rate was minimal. New devices for RSD and its ongoing clinical studies are cited. In conclusion, the RSD presents itself as an effective and safe approach to resistant hypertension. Results from ongoing studies and longer follow-up of these patients are expected to confirm the initial results and put into perspective the expansion of the procedure use in hypertension approach.     

Patient Management with Metallic Valve Prosthesis during Pregnancy and Postpartum Period

Prosthetic thrombosis is a rare complication, but it has high mortality and morbidity. Young women of childbearing age that have prosthetic heart valves are at increased risk of thrombosis during pregnancy due to changes in coagulation factors. Anticoagulation with adequate control and frequent follow-up if pregnancy occurs must be performed in order to prevent complications related to anticoagulant use. Surgery remains the treatment of choice for prosthetic heart valve thrombosis in most clinical conditions.Patients with metallic prosthetic valves have an estimated 5% risk of thrombosis during pregnancy and maternal mortality of 1.5% related to the event. Anticoagulation with vitamin K antagonists during pregnancy is related to varying degrees of complications at each stage of the pregnancy and postpartum periods. Warfarin sodium crosses the placental barrier and when used in the first trimester of pregnancy is a teratogenic agent, causing 1-3% of malformations characterized by fetal warfarin syndrome and also constitutes a major cause of miscarriage in 10-30% of cases. In the third trimester and at delivery, the use of warfarin is associated with maternal and neonatal bleeding in approximately 5 to 15% of cases, respectively. On the other hand, inadequate anticoagulation, including the suspension of the oral anticoagulants aiming at fetal protection, carries a maternal risk of about 25% of metallic prosthesis thrombosis, particularly in the mitral valve. This fact is also due to the state of maternal hypercoagulability with activation of coagulation factors V, VI, VII, IX, X, platelet activity and fibrinogen synthesis, and decrease in protein S levels.The Registry of Pregnancy and Cardiac Disease (ROPAC), assessing 212 pregnant women with metal prosthesis, showed that prosthesis thrombosis occurred in 10 (4.7%) patients and maternal hemorrhage in 23.1%, concluding that only 58% of patients with metallic prosthesis had a complication-free pregnancy^1-7.There are controversies about the best anticoagulation regimen during pregnancy, childbirth and postpartum of women with metallic valve prosthesis. There are no guidelines about the best single or combined treatment option considering the presumed risk of thrombosis, because there is no evidence regarding maternal effectiveness while taking fetal protection into account. Current recommendations, based on the literature, have been the replacement of warfarin sodium in the first trimester of pregnancy by low-molecular weight heparin (LMWH) until the 12^th week of pregnancy. After this gestational age, warfarin is reintroduced until the 36^th week of gestation and then replaced again by LMWH 24 hours before delivery⁸. The target INR (International Normalized Ratio) during pregnancy should be 2.5 to 3.5 (mean 3.0) when it is mitral prosthesis, and 2.0 to 3.0 when it is aortic prosthesis, values that give the highest maternal protection rates (5.7% risk of death or thromboembolism) compared with heparine⁸. Published review of pregnant women with prosthetic outcomes showed that warfarin provides better protection than heparin as prophylaxis of thromboembolic events in women with metal prostheses, but with greater risk of embryopathy⁹. However, a retrospective, observational study with 3 anticoagulation regimens: enoxaparin before 6 weeks of pregnancy, between 6‑12 weeks or oral anticoagulants throughout the pregnancy, showed that with the use of enoxaparin, thromboembolic complications were seen in 14.9% and most of them were related to subtherapeutic doses, verified through the measurement of anti-factor Xa¹⁰. The anticoagulation regimen at subtherapeutic levels is the main cause of valve thrombosis, being found in up to 93% of cases, regardless of the regimen used^11,12. The risk of thrombosis is probably lower if the anticoagulant dose is appropriate and varies according to the type and position of the metal valve, also taking into consideration the patient''s risk factors.Data from the literature^1,8,9, warn about the inefficiency of using subcutaneous unfractionated heparin (UFH) in preventing metal prosthetic valve thrombosis during pregnancy, due to difficulties in attaining effective anticoagulation, its control and patient adherence to the drug. However, in services that choose this alternative, it is recommended that UFH be initiated at high doses (17,500-20,000 IU 2xday/subcutaneously) and controlled by activated partial prothrombin time (aPTT), which should be twice the control value, remembering that response to heparin is modified by the physiological state of maternal hypercoagulability. When the LMWH is selected, the dose should be administered every 12 hours, subcutaneously, based on the control of the anti-factor Xa between 0.8‑1.2 U/ml, which should be determined after 4-6h of use. Factors that should be taken into account in deciding the best anticoagulant therapy include: patient preferences, expertise of the attending physician and availability of medication level monitoring^11-14 (

不稳定型心绞痛患者凝血纤溶活性及冠状动脉斑块形态的关系及其临床意义

目的探讨不稳定性心绞痛患者不同形态斑块的稳定性及对疾病转归的预测价值。方法85例不稳定性心绞痛患者根据冠状动脉造影结果分为Ⅰ型病变组（21例）、Ⅱ型病变组（45例）、Ⅲ型病变组（19例），40例冠状动脉造影排除冠心病者为对照组，均测定血浆Ⅶ因子凝血活性及组织型纤溶酶原激活物、纤溶酶原激活物抑制物、纤维蛋白原和D二聚体值；其中56例不稳定型心绞痛患者随诊一年，观测预后。结果不稳定性心绞痛患者血浆凝血纤溶因子较正常对照组明显异常，其中Ⅱ型病变组Ⅶ因子凝血活性、纤维蛋白原、纤溶酶原激活物抑制物较其他两组明显升高、组织型纤溶酶原激活物有所下降（P〈0．05）；D二聚体改变无显著性（P〉0．05）。一年内急性心肌梗塞和心源性猝死的发生率亦明显高于其它两型（P〈0.01）。结论冠状动脉造影不同形态斑块凝血纤溶活性明显不同，可以作为判断不稳定型心绞痛斑块稳定性及疾病转归的重要手段。     

Acute Coronary Syndrome Treatment Costs from the Perspective of the Supplementary Health System

Background

Acute coronary syndrome (ACS) is defined as a “group of clinical symptoms compatible with acute myocardial ischemia”, representing the leading cause of death worldwide, with a high clinical and financial impact. In this sense, the development of economic studies assessing the costs related to the treatment of ACS should be considered.

Objective

To evaluate costs and length of hospital stay between groups of patients treated for ACS undergoing angioplasty with or without stent implantation (stent+ / stent-), coronary artery bypass surgery (CABG) and treated only clinically (Clinical) from the perspective of the Brazilian Supplementary Health System (SHS).

Methods

A retrospective analysis of medical claims of beneficiaries of health plans was performed considering hospitalization costs and length of hospital stay for management of patients undergoing different types of treatment for ACS, between Jan/2010 and Jun/2012.

Results

The average costs per patient were R$ 18,261.77, R$ 30,611.07, R$ 37,454.94 and R$ 40,883.37 in the following groups: Clinical, stent-, stent+ and CABG, respectively. The average costs per day of hospitalization were R$ 1,987.03, R$ 4,024.72, R$ 6,033.40 and R$ 2,663.82, respectively. The average results for length of stay were 9.19 days, 7.61 days, 6.19 days and 15.20 days in these same groups. The differences were significant between all groups except Clinical and stent- and between stent + and CABG groups for cost analysis.

Conclusion

Hospitalization costs of SCA are high in the Brazilian SHS, being significantly higher when interventional procedures are required.     

Diabetes Mellitus and Glucose as Predictors of Mortality in Primary Coronary Percutaneous Intervention

Background

Diabetes mellitus and admission blood glucose are important risk factors for mortality in ST segment elevation myocardial infarction patients, but their relative and individual role remains on debate.

Objective

To analyze the influence of diabetes mellitus and admission blood glucose on the mortality of ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention.

Methods

Prospective cohort study including every ST segment elevation myocardial infarction patient submitted to primary coronary percutaneous intervention in a tertiary cardiology center from December 2010 to May 2012. We collected clinical, angiographic and laboratory data during hospital stay, and performed a clinical follow-up 30 days after the ST segment elevation myocardial infarction. We adjusted the multivariate analysis of the studied risk factors using the variables from the GRACE score.

Results

Among the 740 patients included, reported diabetes mellitus prevalence was 18%. On the univariate analysis, both diabetes mellitus and admission blood glucose were predictors of death in 30 days. However, after adjusting for potential confounders in the multivariate analysis, the diabetes mellitus relative risk was no longer significant (relative risk: 2.41, 95% confidence interval: 0.76 - 7.59; p-value: 0.13), whereas admission blood glucose remained and independent predictor of death in 30 days (relative risk: 1.05, 95% confidence interval: 1.02 - 1.09; p-value ≤ 0.01).

Conclusion

In ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention, the admission blood glucose was a more accurate and robust independent predictor of death than the previous diagnosis of diabetes. This reinforces the important role of inflammation on the outcomes of this group of patients.