Cardioprotective effect of ornitho-kinin in an anesthetized, open-chest chicken model of acute coronary occlusion

The generation of bradykinin (BK; Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) in blood and kallidin (Lys-BK) in tissues by the action of the kallikrein-kinin system has received little attention in non-mammalian vertebrates. In mammals, kallidin can be generated by the coronary endothelium and myocytes in response to ischemia, mediating cardioprotective events. The plasma of birds lacks two key components of the kallikrein-kinin system: the low molecular weight kininogen and a prekallikrein activator analogous to mammalian factor XII, but treatment with bovine plasma kallikrein generates ornitho-kinin [Thr6,Leu8]-BK. The possible cardioprotective effect of ornitho-kinin infusion was investigated in an anesthetized, open-chest chicken model of acute coronary occlusion. A branch of the left main coronary artery was reversibly ligated to produce ischemia followed by reperfusion, after which the degree of myocardial necrosis (infarct size as a percent of area at risk) was assessed by tetrazolium staining. The iv injection of a low dose of ornitho-kinin (4 µg/kg) reduced mean arterial pressure from 88 ± 12 to 42 ± 7 mmHg and increased heart rate from 335 ± 38 to 402 ± 45 bpm (N = 5). The size of the infarct was reduced by pretreatment with ornitho-kinin (500 µg/kg infused over a period of 5 min) from 35 ± 3 to 10 ± 2% of the area at risk. These results suggest that the physiological role of the kallikrein-kinin system is preserved in this animal model in spite of the absence of two key components, i.e., low molecular weight kininogen and factor XII.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Rosuvastatin prevents myocardial necrosis in an experimental model of acute myocardial infarction

Dyslipidemia is related to the progression of atherosclerosis and is an important risk factor for acute coronary syndromes. Our objective was to determine the effect of rosuvastatin on myocardial necrosis in an experimental model of acute myocardial infarction (AMI). Male Wistar rats (8-10 weeks old, 250-350 g) were subjected to definitive occlusion of the left anterior descending coronary artery to cause AMI. Animals were divided into 6 groups of 8 to 11 rats per group: G1, normocholesterolemic diet; G2, normocholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days after AMI; G3, normocholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days before and after AMI; G4, hypercholesterolemic diet; G5, hypercholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days after AMI; G6, hypercholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days before and after AMI. Left ventricular function was determined by echocardiography and percent infarct area by histology. Fractional shortening of the left ventricle was normal at baseline and decreased significantly after AMI (P < 0.05 in all groups), being lower in G4 and G5 than in the other groups. No significant difference in fractional shortening was observed between G6 and the groups on the normocholesterolemic diet. Percent infarct area was significantly higher in G4 than in G3. No significant differences were observed in infarct area among the other groups. We conclude that a hypercholesterolemic diet resulted in reduced cardiac function after AMI, which was reversed with rosuvastatin when started 30 days before AMI. A normocholesterolemic diet associated with rosuvastatin before and after AMI prevented myocardial necrosis when compared with the hypercholesterolemic condition.

Acute coronary syndrome associated with continuous 5-fluorouracil infusion in a patient with metastatic colorectal cancer-a case report with a discussion on this clinical dilemma

Introduction: 5-Fluorouracil (5-FU) is considered to be the backbone of colorectal cancer (CRC) systemic therapy since the great majority of recommended regimens include its administration. A clinical picture consisting of chest pain, sometimes cardiac enzyme elevation, electrocardiogram abnormalities consistent with myocardial ischemia, and normal coronary angiogram associated with 5-FU administration have been infrequently reported. The clinical dilemma is: Which chemotherapy regimen should we use in CRC patients with a previous acute coronary syndrome (ACS) associated with 5-FU? Case Report: We describe the case of a 55-year-old otherwise healthy woman with metastatic colon adenocarcinoma who presented an ACS probably secondary to arterial vasospasm while receiving continuous intravenous 5-FU infusion (mFOLFOX6 regimen). After the ACS, the patient was treated with raltitrexate plus oxaliplatin (TOMOX) and subsequently with irinotecan plus cetuximab with no other cardiac event. Conclusion: The risk of cardiotoxicity associated with 5-FU is low but real. The probable mechanism is arterial vasospasm, as suggested by our case report. Both the use of the TOMOX regimen and irinotecan plus cetuximab seems to be safe regimens to be considered in this clinical scenario. © 2009 Humana Press Inc.

Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome

Purpose: To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS).Methods: This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05) in PATIENTS.Results: BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26-3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15-9.40, p<0.001).Conclusions: After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.

In-hospital death in acute coronary syndrome was related to admission glucose in men but not in women

Background: Admission hyperglycaemia is associated with mortality in patients with acute coronary syndrome (ACS), but controversy exists whether hyperglycaemia uniformly affects both genders. We evaluated coronary risk factors, gender, hyperglycaemia and their effect on hospital mortality. Methods: 959 ACS patients (363 women and 596 men) were grouped based on glycaemia >= or < 200 mg/dL and gender: men with glucose < 200 mg/dL (menG-); women with glucose < 200 mg/dL (womenG-); men with glucose >= 200 mg/dL (menG+); and women with glucose >= 200 mg/dL (womenG+). A logistic regression analysis compared the relation between gender and glycaemia groups and death, adjusted for coronary risk factors and laboratory data. Results group: menG- had lower mortality than menG+ (OR = 0.172, IC95% 0.062-0.478), and womenG+ (OR = 0.275, IC95% 0.090-0.841); womenG- mortality was lower than menG+ (OR = 0.230, IC95% 0.074-0.717). No difference was found between menG+ vs womenG+ (p = 0.461), or womenG- vs womenG+ (p = 0.110). Age (OR = 1.067, IC95% 1.031-1.104), EF (OR = 0.942, IC95% 0.915-0.968), and serum creatinine (OR = 1.329, IC95% 1.128-1.566) were other independent factors related to in-hospital death. Conclusions: Death was greater in hyperglycemic men compared to lower blood glucose men and women groups, but there was no differences between women groups in respect to glycaemia after adjustment for coronary risk factors.

Performance of rest myocardial perfusion imaging in the management of acute chest pain in the emergency room in developing nations (PREMIER trial)

Background. Rest myocardial perfusion imaging (MPI) is effective in managing patients with acute chest pain in developed countries. We aimed to define the role and feasibility of rest MPI in low-to-middle income countries. Methods and Results. Low-to-intermediate risk patients (n = 356) presenting with chest pain to ten centers in eight developing countries were injected with a Tc-99m-based tracer, and standard imaging was performed. The primary outcome was a composite of death, non-fatal myocardial infarction (MI), recurrent angina, and coronary revascularization at 30 days. Sixty-nine patients had a positive MPI (19.4%), and 52 patients (14.6%) had a primary outcome event. An abnormal rest-MPI result was the only variable which independently predicted the primary outcome [adjusted odds ratio (OR) 8.19, 95% confidence interval 4.10-16.40, P = .0001]. The association of MPI result and the primary outcome was stronger (adjusted OR 17.35) when only the patients injected during pain were considered. Rest-MPI had a negative predictive value of 92.7% for the primary outcome, improving to 99.3% for the hard event composite of death or MI. Conclusions. Our study demonstrates that rest-MPI is a reliable test for ruling out MI when applied to patients in developing countries. (J Nucl Cardiol 2012;19:1146-53.)

Coronary plaque rupture in patients with myocardial infarction after noncardiac surgery: Frequent and dangerous

Purpose: The pathophysiology of acute coronary syndromes (ACS) after noncardiac surgery is not established yet. Thrombosis over a vulnerable plaque or decreased oxygen supply secondary to anemia or hypotension may be involved. The purpose of this study was to investigate the pathophysiology of ACS complicating noncardiac surgery. Methods: Clinical and angiographic data were prospectively recorded into a database for 120 consecutive patients that had an ACS after noncardiac surgery (PACS), for 120 patients with spontaneous ACS (SACS), and 240 patients with stable coronary artery disease (CAD). Coronary lesions with obstructions greater than 50% were classified based on two criteria: Ambrose's classification and complex morphology. The presence of Ambrose's type II or complex lesions were compared between the three groups. Results: We analyzed 1470 lesions in 480 patients. In PACS group, 45% of patients had Ambrose's type II lesions vs. 56.7% in SACS group and 16.4% in stable CAD group (P < 0.001). Both PACS and SACS patients had more complex lesions than patients in stable CAD group (56.7% vs. 79.2% vs. 31.8%, respectively; P < 0.001). Overall, the independent predictors of plaque rupture were being in the group PACS (P < 0.001, OR 2.86; CI, 1.82-4.52 for complex lesions and P < 0.001, OR 3.43; CI, 2.1-5.6 for Ambrose's type II lesions) or SACS (P < 0.001, OR 8.71; CI, 5.15-14.73 for complex lesions and P < 0.001, OR 5.99; CI, 3.66-9.81 for Ambrose's type II lesions). Conclusions: Nearly 50% of patients with perioperative ACS have evidence of coronary plaque rupture, characterizing a type 1 myocardial infarction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome

AIM: to assess the clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome (ACS) according to its clinical manifestation. METHODS: data were collected from 234 patients, hospitalized between May 2006 and July 2009 due to the first episode of an ACS, by consulting their medical records. RESULTS: 234 patients were hospitalized, 140 (59.8%) due to Acute Myocardial Infarction (AMI). In the group with AMI, 19.3% presented complications, against 12.8% in the group with Unstable Angina (UA) (p=0.19). Angioplasty levels were higher among patients with AMI than with UA (p=0.02) and coronary artery bypass graft surgery was more frequent among UA patients (p=0.03). The majority (227; 97%) survived after the coronary event. Among the seven patients who died during the hospitalization, four had AMI (2.9%) and three UA (3.2%). CONCLUSIONS: A larger number of complications were found among infarction victims and the accomplishment of coronary artery bypass graft surgery differed between the groups.

Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Combined Evaluation of ST-segment Elevation in lead AVR and ST-segment Depression in other Leads Enhances Prediction of in-hospital Cardiovascular Death in Patients with Non ST-segment Elevation Acute Coronary Syndrome

Objective: To investigate the prognostic significance of ST-segment elevation (STE) in aVR associated with ST-segment depression (STD) in other leads in patients with non-STE acute coronary syndrome (NSTE-ACS). Background: In NSTE-ACS patients, STD has been extensively associated with severe coronary lesions and poor outcomes. The prognostic role of STE in aVR is uncertain. Methods: We enrolled 888 consecutive patients with NSTE-ACS. They were divided into two groups according to the presence or not on admission ECG of aVR STE≥ 1mm and STD (defined as high risk ECG pattern). The primary and secondary endpoints were: in-hospital cardiovascular (CV) death and the rate of culprit left main disease (LMD). Results: Patients with high risk ECG pattern (n=121) disclosed a worse clinical profile compared to patients (n=575) without [median GRACE (Global-Registry-of-Acute-Coronary-Events) risk score =142 vs. 182, respectively]. A total of 75% of patients underwent coronary angiography. The rate of in-hospital CV death was 3.9%. On multivariable analysis patients who had the high risk ECG pattern showed an increased risk of CV death (OR=2.88, 95%CI 1.05-7.88) and culprit LMD (OR=4.67,95%CI 1.86-11.74) compared to patients who had not. The prognostic significance of the high risk ECG pattern was maintained even after adjustment for the GRACE risk score (OR = 2.28, 95%CI:1.06-4.93 and OR = 4.13, 95%CI:2.13-8.01, for primary and secondary endpoint, respectively). Conclusions: STE in aVR associated with STD in other leads predicts in-hospital CV death and culprit LMD. This pattern may add prognostic information in patients with NSTE-ACS on top of recommended scoring system.

Key issues in diagnosing and treating acute aortic syndromes: results from the metropolitan area of Bologna network

Background: Survival of patients with Acute Aortic Syndrome (AAS) may relate to the speed of diagnosis. Diagnostic delay is exacerbated by non classical presentations such as myocardial ischemia or acute heart failure (AHF). However little is known about clinical implications and pathophysiological mechanisms of Troponin T elevation and AHF in AAS. Methods and Results: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Troponin T values (either standard or high sensitivity assay, HS) were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or HS assay respectively, p = 0.001). Troponin positivity was associated with a twofold increased risk of long in-hospital diagnostic time (OR 1.92, 95% CI 1.05-3.52, p = 0.03), but not with in-hospital mortality. The combination of positive troponin and ACS-like ECG abnormalities resulted in a significantly increased risk of inappropriate therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). Patients with AHF were identified by the presence of dyspnea as presentation symptom or radiological signs of pulmonary congestion or cardiogenic shock. The overall frequency of AHF was 28 % (32% type A vs. 20% type B AAS, p = 0.01). AHF was due to a variety of pathophysiological mechanisms including cardiac tamponade (26%), aortic regurgitation (25%), myocardial ischemia (17%), hypertensive crisis (10%). AHF was associated with increased surgical delay and with increased risk of in-hospital death (adjusted OR 1.97 95% CI1.13-3.37,p=0.01). Conclusions: Troponin positivity (particularly HS) was a frequent finding in AAS. Abnormal troponin values were strongly associated with ACS-like ECG findings, in-hospital diagnostic delay, and inappropriate therapy. AHF was associated with increased surgical delay and was an independent predictor of in-hospital mortality.

Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years

BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events.

Sudden cardiac arrest during acute coronary occlusion - who is at risk?

Many people with acute myocardial infarction die from sudden cardiac arrest before reaching the hospital. The current clinical understanding of the mechanisms and risk factors surrounding sudden cardiac death is limited. However, 2 factors related to sudden death, namely the occluded coronary vessel (right coronary, left circumflex, or left anterior descending artery) and the extent of collateral circulation, are of potential relevance. Recent data suggest that the risk differs between the different coronary arteries and that coronary collateral circulation seems to have an important protective 'antiarrhythmic' effect. This editorial will address possible mechanisms and potential implications in clinical practice.

Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularization

Coronary artery disease remains the leading cause of mortality in most industrialized countries, although age-standardized mortality related to coronary artery disease (CAD) has decreased by more than 40% during the last two decades. Coronary atherosclerosis may cause angina pectoris, myocardial infarction, heart failure, arrhythmia, and sudden death. Medical management of atherosclerosis and its manifestation aims at retardation of progression of plaque formation, prevention of plaque rupture, and subsequent events and treatment of symptoms, when these occur as well as treatment of the sequelae of the disease. Revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is performed as treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia. In high-risk patients with acute coronary syndromes (ACS), a routine invasive strategy with revascularization in most patients provides the best outcome with a significant reduction in death and myocardial infarction compared with an initial conservative strategy. Conversely, the benefit of revascularization among patients with chronic stable CAD has been called into question. This review will provide information that revascularization exerts favourable effects on symptoms, quality of life, exercise capacity, and survival, particularly in those with extensive CAD and documented moderate-to-severe ischaemia. Accordingly, CABG and PCI should be considered a valuable adjunct rather than an alternative to medical therapy.