Association of Interleukin 8 and Myocardial Recovery in Patients with ST-Elevation Myocardial Infarction Complicated by Acute Heart Failure

Background

No data from controlled trials exists regarding the inflammatory response in patients with de novo heart failure (HF) complicating ST-elevation myocardial infarction (STEMI) and a possible role in the recovery of contractile function. We therefore explored the time course and possible associations between levels of inflammatory markers and recovery of impaired left ventricular function as well as levosimendan treatment in STEMI patients in a substudy of the LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial.

Methods

A total of 61 patients developing HF within 48 hours after a primary PCI-treated STEMI were randomised double-blind to a 25 hours infusion of levosimendan or placebo. Levels of IL-6, CRP, sIL-6R, sgp130, MCP-1, IL-8, MMP-9, sICAM-1, sVCAM-1 and TNF-α were measured at inclusion (median 22 h, interquartile range (IQR) 14, 29 after PCI), on day 1, day 2, day 5 and 6 weeks. Improvement in left ventricular function was evaluated as change in wall motion score index (WMSI) by echocardiography.

Results

Only circulating levels of IL-8 at inclusion were associated with change in WMSI from baseline to 6 weeks, r = ÷0.41 (p = 0.002). No association, however, was found between IL-8 and WMSI at inclusion or peak troponin T. Furthermore, there was a significant difference in change in WMSI from inclusion to 6 weeks between patients with IL-8 levels below, compared to above median value, ÷0.44 (IQR÷0.57, ÷0.19) vs. ÷0.07 (IQR÷0.27, 0.07), respectively (p<0.0001). Levosimendan did not affect the levels of inflammary markers compared to control.

Conclusion

High levels of IL-8 in STEMI patients complicated with HF were associated with less improvement in left ventricular function during the first 6 weeks after PCI, suggesting a possible role of IL-8 in the reperfusion-related injury of post-ischemic myocardium. Further studies are needed to confirm this hypothesis.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00324766","term_id":"NCT00324766"}}NCT00324766     

Interleukin-18 as a Therapeutic Target in Acute Myocardial Infarction and Heart Failure

Interleukin 18 (IL-18) is a proinflammatory cytokine in the IL-1 family that has been implicated in a number of disease states. In animal models of acute myocardial infarction (AMI), pressure overload, and LPS-induced dysfunction, IL-18 regulates cardiomyocyte hypertrophy and induces cardiac contractile dysfunction and extracellular matrix remodeling. In patients, high IL-18 levels correlate with increased risk of developing cardiovascular disease (CVD) and with a worse prognosis in patients with established CVD. Two strategies have been used to counter the effects of IL-18:IL-18 binding protein (IL-18BP), a naturally occurring protein, and a neutralizing IL-18 antibody. Recombinant human IL-18BP (r-hIL-18BP) has been investigated in animal studies and in phase I/II clinical trials for psoriasis and rheumatoid arthritis. A phase II clinical trial using a humanized monoclonal IL-18 antibody for type 2 diabetes is ongoing. Here we review the literature regarding the role of IL-18 in AMI and heart failure and the evidence and challenges of using IL-18BP and blocking IL-18 antibodies as a therapeutic strategy in patients with heart disease.     

Financial Stress and Outcomes after Acute Myocardial Infarction

Background

Little is known about the association between financial stress and health care outcomes. Our objective was to examine the association between self-reported financial stress during initial hospitalization and long-term outcomes after acute myocardial infarction (AMI).

Materials and Methods

We used Prospective Registry Evaluating Myocardial Infarction: Event and Recovery (PREMIER) data, an observational, multicenter US study of AMI patients discharged between January 2003 and June 2004. Primary outcomes were disease-specific and generic health status outcomes at 1 year (symptoms, function, and quality of life (QoL)), assessed by the Seattle Angina Questionnaire [SAQ] and Short Form [SF]-12. Secondary outcomes included 1-year rehospitalization and 4-year mortality. Hierarchical regression models accounted for patient socio-demographic, clinical, and quality of care characteristics, and access and barriers to care.

Results

Among 2344 AMI patients, 1241 (52.9%) reported no financial stress, 735 (31.4%) reported low financial stress, and 368 (15.7%) reported high financial stress. When comparing individuals reporting low financial stress to no financial stress, there were no significant differences in post-AMI outcomes. In contrast, individuals reporting high financial stress were more likely to have worse physical health (SF-12 PCS mean difference −3.24, 95% Confidence Interval [CI]: −4.82, −1.66), mental health (SF-12 MCS mean difference: −2.44, 95% CI: −3.83, −1.05), disease-specific QoL (SAQ QoL mean difference: −6.99, 95% CI: −9.59, −4.40), and be experiencing angina (SAQ Angina Relative Risk = 1.66, 95%CI: 1.19, 2.32) at 1 year post-AMI. While 1-year readmission rates were increased (Hazard Ratio = 1.50; 95%CI: 1.20, 1.86), 4-year mortality was no different.

Conclusions

High financial stress is common and an important risk factor for worse long-term outcomes post-AMI, independent of access and barriers to care.     

Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction

Objectives

There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.

Methods

We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight–6:00 A.M., 6:00 A.M.–noon, noon–6:00 P.M. and 6:00 P.M.–midnight. We used peak creatine kinase as a surrogate marker of infarct size.

Results

Midnight–6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight–6:00 A.M. patients and lowest among 6:00 A.M.–noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight–6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.–noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).

Conclusion

We observed a circadian peak and nadir in infarct size during STEMI onset from midnight–6:00A.M and 6:00A.M.–noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.     

The Relation between Serum Phosphorus Levels and Clinical Outcomes after Acute Myocardial Infarction

Background

Elevated serum phosphorus levels have been linked with cardiovascular disease and mortality with conflicting results, especially in the presence of normal renal function.

Methods

We studied the association between serum phosphorus levels and clinical outcomes in 1663 patients with acute myocardial infarction (AMI). Patients were categorized into 4 groups based on serum phosphorus levels (<2.50, 2.51–3.5, 3.51–4.50 and >4.50 mg/dL). Cox proportional-hazards models were used to examine the association between serum phosphorus and clinical outcomes after adjustment for potential confounders.

Results

The mean follow up was 45 months. The lowest mortality occurred in patients with serum phosphorus between 2.5–3.5 mg/dL, with a multivariable-adjusted hazard ratio of 1.24 (95% CI 0.85–1.80), 1.35 (95% CI 1.05–1.74), and 1.75 (95% CI 1.27–2.40) in patients with serum phosphorus of <2.50, 3.51–4.50 and >4.50 mg/dL, respectively. Higher phosphorus levels were also associated with increased risk of heart failure, but not the risk of myocardial infarction or stroke. The effect of elevated phosphorus was more pronounced in patients with chronic kidney disease (CKD). The hazard ratio for mortality in patients with serum phosphorus >4.5 mg/dL compared to patients with serum phosphorus 2.50–3.50 mg/dL was 2.34 (95% CI 1.55–3.54) with CKD and 1.53 (95% CI 0.87–2.69) without CKD.

Conclusion

We found a graded, independent association between serum phosphorus and all-cause mortality and heart failure in patients after AMI. The risk for mortality appears to increase with serum phosphorus levels within the normal range and is more prominent in the presence of CKD.     

不同剂量氯吡格雷治疗急性ST段抬高心肌梗死的临床研究

目的:观察标准治疗基础上联合不同剂量氯吡格雷治疗急性ST段抬高心肌梗死的疗效及安全性。方法:2004年9月至2008年3月就诊我院的124例12小时以内发病的ST段抬高型心肌梗死患者,随机分为3组,3组均在入院后前3天给予阿司匹林300mg/d,此后给予阿司匹林100mg/d,A组常规不给予氯吡格雷治疗,B组给予氯吡格雷75mg/d,C组入院即刻给予氯吡格雷300mg,继之75 mg/d治疗,随访30天。观察溶栓血管再通率、梗死后心绞痛发作、心力衰竭事件及死亡、再发心肌梗死、或脑卒中的联合终点。结果:与A组相比,B组、C组患者溶栓成功率提高、梗死后心绞痛发作减少。P<0.05:进一步分析发现C组与B组差异无统计学意义,P>0.05。三组均无主要和次要出血事件发生,轻微出血发生率无统计学差异,P<0.05。结论:ST段抬高的急性心肌梗死患者在标准治疗的基础上早期加用氯吡格雷75 mg/d或先予300 mg负荷量,继之75 mg/d口服,均可提高溶栓成功率,降低梗死后心绞痛发生,而氯吡格雷负荷剂量组并不优于普通剂量组,且两组安全耐受性好。     

Mechanical Ventilation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Retrospective Observational Study

Purpose

Patients with acute myocardial infarction (AMI) and respiratory impairment may be treated with either invasive or non-invasive mechanical ventilation (MV). However, there has been little testing of non-invasive MV in the setting of AMI. Our objective was to evaluate the incidence and associated clinical outcomes of patients with AMI who were treated with non-invasive or invasive MV.

Methods

This was a retrospective observational study in which consecutive patients with AMI (n = 1610) were enrolled. The association between exclusively non-invasive MV, invasive MV and outcomes was assessed by multivariable models.

Results

Mechanical ventilation was used in 293 patients (54% invasive and 46% exclusively non-invasive). In-hospital mortality rates for patients without MV, with exclusively non-invasive MV, and with invasive MV were 4.0%, 8.8%, and 39.5%, respectively (P<0.001). The median lengths of hospital stay were 6 (5.8–6.2), 13 (11.2–4.7), and 28 (18.0–37.9) days, respectively (P<0.001). Exclusively non-invasive MV was not associated with in-hospital death (adjusted HR = 0.90, 95% CI 0.40–1.99, P = 0.79). Invasive MV was strongly associated with a higher risk of in-hospital death (adjusted HR = 3.07, 95% CI 1.79–5.26, P<0.001).

Conclusions

In AMI setting, 18% of the patients required MV. Almost half of these patients were treated with exclusively non-invasive strategies with a favorable prognosis, while patients who needed to be treated invasively had a three-fold increase in the risk of death. Future prospective randomized trials are needed to compare the effectiveness of invasive and non-invasive MV for the initial approach of respiratory failure in AMI patients.     

通络药物对心梗后心衰大鼠非梗死区心肌纤维化的影响

目的：探讨不同剂量芪苈强心胶囊对心衰模型大鼠非梗死区胶原蛋白分子表达的影响。方法：将通过结扎冠状动脉左前降支并饲养4周的56只心衰模型鼠随机分成4组：心衰对照组（MI-C）、转换酶抑制剂雷米普利治疗组（MI-R,10mg／kg．d）、芪苈强心小剂量组（MI—S,0．25g／kg．d）以及芪苈强心大剂量组（MI—L,1．0g／kg．d）。同步药物干预4周后,ELISA法检测Ang II水平、RT—PCR检测非梗死区胶原-ImRNA。结果：血清中AngII的浓度：与心力衰竭对照组比较,假手术组、雷米普利组、大剂量芪苈强心组和小剂量芪苈强心组均明显降低（P〈0．05）。其中,大剂量芪苈强心组比雷米普利组明显减低,差异具显著性（P〈0．05）;而小剂量芪苈强心组与雷米普利组水平接近,差异无显著性（P〈0．05）。非梗死区胶原-ImRNA的表达：与心衰对照组比较,假手术组、雷米普利组、大剂量芪苈强心组,小剂量芪苈强心组表达均下调,差别具显著性（P〈0．05）;大剂量芪苈强心组与雷米普利组接近,差别无显著性（P〉0．05）;小剂量芪苈强心组高于大剂量芪苈强心和雷米普利组,差别具有显著性（P〈0．05）。结论：芪苈强心胶囊能够明显地减少心梗后心衰非梗死区胶原分子的合成,并具有明显的剂量依赖性。     

PCI术前与术后主动脉内球囊反搏治疗急性心肌梗死合并心功能不全患者的疗效比较

目的:比较急性心肌梗死合并心功能不全患者冠状动脉介入(PCI)术前及术后植入主动脉内球囊反搏术(IABP)的效果及其安全性.方法:选择50例2010年1月至2011年6月在南京市第一医院CCU病房应用IABP治疗的急性心肌梗死患者,分为两组,A组为术前组,B组为术后组,各25例,观察并比较两组的即刻病情改善率、住院期间并发症及术后30天心功能、主要心血管事件(MACE)发生率.结果:A组IABP即刻病情改善显著高于B组(36％ vs.12％,P＜0.05).两组住院期间并发症的发生率均无统计学差异(P＞0.05).术后30天,A组LVEF显著低于B组(40.2± 7.7％vs.35.6±5.0％,P＜0.05).MACE事件,A组非致死性心肌梗死、再次PCI/CABG术及死亡发生率低于B组,其中A组死亡率显著低于B组,差异有统计学意义(58％vs.32％,P＜0.05).结论:PCI术前植入IABP对于急性心肌梗死合并心功能不全患者的疗效优于PCI术后植入,且不提高并发症的发生率.     

Advanced Heart Block During Acute Myocardial Infarction Treated with an Electrode Pacing Catheter

The mortality rate is high from advanced atrioventricular block associated with acute myocardial infarction. There is reason to believe that if in these patients the hearts are electrically paced with an endocardial pacing catheter, the mortality rate can be considerably decreased. Five patients in second- and third-degree heart block associated with acute myocardial infarction were paced with a considerable lowering of the expected mortality rate. Twenty-three cases from the literature are also presented and discussed. A silastic bipolar electrode catheter was used in these five cases. Four of the five cases returned to normal sinus rhythm within the first 10 days. The average duration of pacing was 6.7 days. It is the opinion of the author that second- and third-degree heart block associated with acute myocardial infarction should have a pacing catheter introduced at the earliest possible moment for continuous or demand endocardial pacing.     

National Assessment of Statin Therapy in Patients Hospitalized with Acute Myocardial Infarction: Insight from China PEACE-Retrospective AMI Study, 2001, 2006, 2011

BackgroundStatin therapy is among the most effective treatments to improve short- and long-term mortality after acute myocardial infarction. The use of statin, and the intensity of their use, has not been described in acute myocardial infarction patients in China, a country with a rapidly growing burden of cardiovascular disease.ConclusionsThe use of statin therapy has dramatically increased over the past decade in Chinese patients with acute myocardial infarction. However, half of patients still did not receive intensive statin therapy in 2011.Given that guidelines strongly endorse intensive statin therapy for acute myocardial infarction patients, initiatives promoting the use of statin therapy, with attention to treatment intensity, would support further improvements in practice.     

大鼠急性心肌梗死模型的制备及对肌钙蛋白T的影响

目的探讨建立大鼠急性心肌梗死（AMI）模型的方法,研究心肌梗死大鼠血浆中肌钙蛋白T（cTn-T）的动态变化。方法大鼠经结扎左冠状动脉前降支造成心肌梗死,建立稳定的心肌梗死模型;分别在结扎后31 h、48 h、69 h、168 h检测cTn-T含量和计算心肌梗死重量指数。结果成功制备心肌梗死大鼠模型,并对常规技术进行改进,降低动物死亡率。大鼠左冠状动脉结扎31 h、48 h模型组与假手术组cTn-T含量差异极显著（P〈0.001）;各时间点心肌梗死重量指数比较,差异极显著（P〈0.001）。cTn-T值与梗死重量指数呈显著性正相关（r=0.90,P〈0.01）。结论结合大鼠心肌梗死程度进一步佐证了模型制备较成功。cTn-T表现出特异性和敏感性,并在31 h最接近达峰时间,有早期诊断心肌梗死的价值,也可作为判断AMI时心肌梗死程度和预后的参考指标。     

新活素联合CRRT治疗急性心力衰竭并发急性肾衰竭的疗效观察

目的:观察新活素联合连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)治疗急性心力衰竭并发急性肾衰竭的临床疗效.方法:选择2011年9月至2012年9月于我院ICU治疗的36例急性心力衰竭并发急性肾衰竭的患者,并将其随机分为3组,分别给予新活素联合CRRT治疗、单独新活素治疗、单独CRRT治疗,比较治疗前后各组患者的Killip分级、左心室射血分数、尿量、BNP、血肌酐及尿素氮、氧合指数、动脉血乳酸值的变化情况.结果:观察组的显效率、有效率及总体有效率均较对照组1和对照组2显著降低,差异均具有显著统计学意义(P＜0.01),对照组1的显效率及总体有效率均明显高于对照组2(P＜0.01),但两组患者的有效率比较无统计学差异(P＞o.05).观察组治疗7天的死亡率明显低于对照组1和对照组2,差异均有显著性(P＜0.01).观察组及对照组2的心肾功能指标均较治疗前明显改善(P＜0.01),且观察组的改善程度明显优于对照组2(P＜0.01),对照组1的心功能指标较治疗前明显改善P＜0.01),但肾功能指标无明显变化(P＞0.05),但尿量显著增加(P＜0.01).结论:新活素联合CRRT治疗组疗效明显优于单独CRRT或新活素治疗组,并可有效降低患者的死亡率.