Missed Heparin-Induced Thrombocytopenia (HIT) Diagnosis in a Patient with Acute Stent Thrombosis.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, characterized by thrombocytopenia and high risk for venous and arterial thrombosis. CASE REPORT We report an unusual case of acute stent thrombosis secondary to delayed HIT. A 74-year-old man with non-ST-segment elevation myocardial infarction had a coronary angiography which revealed 2-vessel disease. A bolus of unfractionated heparin (UFH) was administered at admission and he received fondaparinux during his hospitalization. We performed elective percutaneous coronary intervention (PCI) with stents to LAD and LCx. Two hours after PCI, the patient developed acute pulmonary edema, and repeat angiography revealed an occlusive thrombus in the ostial LAD and the LCx. A turbidimetric assay for the rapid detection of plasma anti-PF4/heparin antibodies was negative. After repeated unsuccessful attempts of balloon angioplasty and continuous thrombosis, the patient was transferred for emergency surgical revascularisation and was treated with additional UFH followed by enoxaparin. Platelets decreased gradually to 38 k/µl 7 days after surgery, at which time enoxaparin was replaced with fondaparinux. The subsequent HIT test results were positive. CONCLUSIONS HIT should be considered in patients with multiple recent exposures to anticoagulants, independent of the platelet count, if there are signs and symptoms of thrombosis.

Platelet to lymphocyte ratio in acute aortic dissection.

BACKGROUND: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet-lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD. METHODS: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched. RESULTS: PLR was significantly higher in group I vs both groups II and III (P < .001). There was an excellent correlation of PLR with neutrophil/lymphocyte ratio (NLR) in all three groups (P < .001 for all). After adjustment for hemoglobin, RDW did not differ but RPR remained significantly higher in group I compared to groups II and III (P < .001). The best cutoff value of PLR to predict dissection was 159 with 53% sensitivity and 86% specificity. No association between PLR, RDW, and RPR and mortality in group I was found. CONCLUSIONS: Indices derived from full cell blood count may provide diagnostic information in patients with AAD; whether these indices may contribute to prognosis assessment should be further investigated.

Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery.

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2% and low logistic EuroScore (3.5 ± 3.2%) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome.

Clinical presentation and management of stable coronary artery disease: insights from the international prospective CLARIFY registry - results from the Greek national cohort.

INTRODUCTION: Coronary artery disease (CAD) is highly prevalent worldwide, yet there is a paucity of data regarding the clinical characteristics and management of outpatients with stable CAD. In this paper, we report the baseline data of the Greek cohort and we compare our national data with the global results of the entire registry, as well as the results from the western European countries. METHODS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis >50%, or chest pain associated with proven myocardial ischemia. A total of 33,283 patients from 45 countries in 4 continents were enrolled between November 2009 and July 2010; of these, 14,726 were from western European countries (Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the United Kingdom) and 559 patients were enrolled in Greece. RESULTS: Compared to their counterparts in western Europe and the entire cohort, Greeks were younger (p<0.0001, p<0.0001, respectively), more predominantly male (p<0.0039, p<0.0001), with a higher body mass index (p<0.0002, p<0.0001) and a larger waist circumference (p<0.0001, p<0.0001), as well as a higher prevalence of family history of CAD (p<0.0008, 0.0005), hyperlipidemia (p<0.0001, p<0.0001) and smoking (p<0.0001, p<0.0001). Noninvasive testing (p<0.0001, p<0.0001, respectively) and coronary angiography (p<0.0001, 0.0013) along with surgical revascularization (CABG) (p<0.0001, 0.0088) were performed more often in Greece. Antiplatelets, b-blockers and lipid lowering medications were used to an equal extent in Greece as in the other two cohorts. CONCLUSION: There are substantial differences in demographics, clinical profiles and treatment in patients with stable CAD within the data set, which are also observed for Greek data. Interestingly, these differences are consistent in relation to the global as well as the western European data.

Left ventricular pseudoaneurysm formation: Two cases and review of the literature.

Left ventricular wall rupture (LVWR) comprises a complication of acute myocardial infarction (AMI). Acute LVWR is a fatal condition, unless the formation of a pseudoaneurysm occurs. Several risk factors have been described, predisposing to LVWR. High index of suspicion and imaging techniques, namely echocardiography and computed tomography, are the cornerstones of timely diagnosis of the condition. As LVWR usually leads to death, emergency surgery is the treatment of choice, resulting in significant reduction in mortality and providing favorable short-term outcomes and adequate prognosis during late follow-up. Herein, we present two patients who were diagnosed with LVWR following AMI, and subsequent pseudoaneurysm formation. In parallel, we review the aforementioned condition.

High homocysteine and low folate concentrations in acute aortic dissection.

BACKGROUND: Biomarkers for monitoring progression and prognosis of thoracic aneurysm are of great interest. Homocysteine (Hcy) induces elastolysis in arterial media and may directly affect fibrillin-1 or collagen whereas lipoprotein (Lp) (a) inhibits elastolysis by reducing activation of matrix metallopeptidase-9. METHODS: We studied 31 consecutive patients with acute aortic dissection (AAD) admitted for emergency surgery (group I, 60 ± 13 years old, 25 men), 30 consecutive patients with chronic aneurysms of the ascending aorta (group II, 67 ± 12 years old, 24 men) and 20 healthy controls (group III, 58 ± 15 years old, 14 men). We evaluated Hcy, folate, B12, Lp(a) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism at baseline. RESULTS: Hcy, folate and B12 differed significantly among the 3 studied groups (P=0.016, P=0.004 and P=0.001, respectively). The levels of Hcy and B12 were significantly higher in group I compared to both groups II and III (P=0.05 and P=0.002, P<0.001 and P=0.017, respectively) and without significant differences between groups II and III (P=0.083 and P=0.124). Folate was significantly lower in group I compared to both groups II and III (P=0.001 and P=0.006, respectively) and without marked difference between groups II and III (P=0.409). No significant difference was found in serum levels of Lp (a) (P=0.074) or among the frequency of MTHFR C677T genotypes. CONCLUSIONS: Patients with AAD present with higher Hcy and lower folate compared to both chronic aneurysms and controls.

Unprotected left main distal bifurcation lesion.

Left main coronary artery disease is a high-risk condition with significant mortality. Currently, bypass surgery is considered the gold-standard treatment for unprotected left main disease. The introduction of drugeluting stents for the treatment of coronary artery disease has proved to reduce the rates of restenosis and, consequently, the need for repeat revascularisation; therefore, recently, percutaneous coronary intervention in the unprotected left main using drug-eluting stents has been considered another therapeutic option for patients at high risk for bypass surgery, or for patients who simply refuse bypass surgery. Based on the updated guidelines on myocardial revascularisation of the European Society of Cardiology, treating left main lesions by angioplasty is feasible and safe in selected patients. In this case report we demonstrate the successful implantation of drug-eluting stents for the treatment of an unprotected left main bifurcation lesion in an 85-year-old patient with high perioperative risk.

Significant peri-operative reduction in plasma osteopontin levels after coronary artery by-pass grafting.

OBJECTIVES: Osteopontin (OPN) is a multifunctional protein associated with vascular injury and has been linked to atherosclerosis and inflammation. We sought to investigate whether OPN changes in relation to coronary artery by-pass grafting (CABG) surgery. DESIGN AND METHODS: We studied 50 consecutive patients (63 ± 10 years old, 6 women and 44 men) undergoing elective CABG. Plasma OPN levels were determined by an enzyme-linked immunosorbent assay at baseline and in 24 and 72 h, post-operatively. Cardiac enzymes - creatine kinase, the MB isoenzyme of creatine kinase, troponin-I- and C-reactive protein (CRP) were also determined at all three time points. RESULTS: OPN levels 72 h post-op decreased significantly compared to pre-op and 24h post-op levels (p<0.001) whereas there was no difference between the pre-op and first post-op values (p=0.57). The relative change in OPN levels between pre-op and 72 h post-op correlated negatively with absolute troponin-I levels at 72 h post-op (-0.51, p=0.005). OPN levels 72 h post-op correlated significantly with CRP at baseline (r=0.73, p=0.002). CONCLUSIONS: OPN plasma concentrations decreased after CABG surgery in the early post-operative period. The significance of this observation needs further investigation.

Anomalous origin of coronary arteries: when one sinus fits all.

A right coronary artery origin from the left coronary sinus and a left coronary origin from the right sinus although rarely encountered during routine cardiac catheterization, they represent two relatively common autopsy findings in young patients suffering sudden cardiac death. The interarterial course of the aberrant artery, between the aortic root and the pulmonary artery has been considered as a malignant variant, because of the higher risk of myocardial ischemia and sudden death. We present two rare cases of ectopic coronary origin from the opposite sinus of Valsalva.

Skeletal muscle abnormalities in chronic heart failure.

Skeletal muscle abnormalities are well-established in patients with heart failure from an early stage in the progression of the disease and contribute to their symptoms and the limitation of physical activity. Heart failure-induced skeletal muscle pathology includes morphologic, histologic, and enzymatic changes along with derangements in skeletal muscle metabolism and autonomic function. These alterations influence both peripheral and ventilatory muscles, are present at rest, and deteriorate during exercise and their occurrence depends upon the severity and the duration of CHF syndrome. Future studies will be needed to elucidate the origin of skeletal "myopathy" and its reversibility, which is associated with improvement in exercise capacity, observed after physical training programs.

Heart type fatty acid binding protein in relation to pharmacologic scintigraphy in coronary artery disease.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a marker of myocardial necrosis, but whether it increases during myocardial ischemia is not known. This study investigated whether serum levels of H-FABP change during adenosine stress testing and nuclear imaging in patients with stable coronary artery disease. METHODS: Thirty stable patients with established coronary artery disease on their medications were studied. Sampling was performed before the stress test, at the end of adenosine infusion, as well as 1, 2 and 3 h after the completion of the infusion. RESULTS: No difference in H-FABP serum levels were found at the five pre-specified time points in the overall group (p=0.99); furthermore, there was no significant difference regardless of the test result--positive (p=1) or negative (p=0.98). CONCLUSIONS: It is concluded that H-FABP does not change significantly during pharmacologic stress testing in patients with known coronary artery disease and there is no difference whether there is inducible ischemia or not.

Gender-specific differences in biomarkers responses to acute coronary syndromes and revascularization procedures.

A growing body of gender-related research in coronary artery disease is beginning to gradually elucidate differences between women and men. In patients presenting with acute coronary syndromes (ACS), these sex differences include varying risk factor profiles, accuracy of diagnostic testing, clinical presentations, treatment practices and outcomes. There is also a differential expression of cardiac biomarkers by sex, which remains unexplained. This paper reviews all the available information on the effect of gender on cardiac biomarkers by search of MEDLINE using the terms gender differences, biomarkers, ACS and revascularization procedures. A better understanding of the sex disparities in biomarkers along with all other clinical information is essential to optimal management and patient care in the future.

Cytokine gene polymorphisms are associated with markers of disease severity and prognosis in patients with idiopathic dilated cardiomyopathy.

AIMS: To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-ß1)+869 T/C (codon10 Leu→Pro), TGF-ß1 +915 G/C (codon25 Arg→Pro), interleukin (IL)-6 -174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 -1082A/G, IL-10 -819T/C and IL-10 -592A/C gene polymorphisms. In homozygous TT patients for TGF-ß1 +869 T/C polymorphism mean VO(2) max was significantly higher than in CC homozygous patients (25.67±6.73ml/kg/min vs. 20.29±6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex (p = 0.009). C carriers of TGF-ß1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III-IV) than non C carriers [OR: 4.25, 95% CI (1.53-11.80), p = 0.006]. Patients GG homozygous for IL-6 -174G/C polymorphism presented greater left ventricle end-systolic (p = 0.018) and end-diastolic (p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism (p = 0.02) and the combination of the TGF-ß1 +869 T/C and TGF-ß1 +915 G/C genotypes were associated with adverse outcome (p = 0.014). CONCLUSION: Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

Ischemia-modified albumin in acute aortic dissection.

BACKGROUND: Acute aortic dissection (AOD) is associated with high mortality and early diagnosis and treatment are essential. Ischemia-modified albumin (IMA) is a marker of myocardial ischemia whereas cardiac enzymes are released when myocardial necrosis occurs. We investigated, for the first time, whether IMA increases in AOD either at presentation or after surgery. METHODS: We studied 46 consecutive patients with documented AOD; we also evaluated 13 consecutive patients with dilated ascending aortas scheduled for elective surgery and admitted for preoperative coronary angiography; 46 age-matched normal subjects served as controls. Only patients with acute onset of symptoms were included. We evaluated IMA, cardiac enzymes, N-terminal pro-B-type natriuretic peptide, albumin, C-reactive protein (CRP), and D-dimers on admission, 24 hr post-operatively and 4 days post-operatively. Duration from symptom onset to the first sample was 23±17 hr. RESULTS: IMA did not differ between patients with AOD at presentation (93±19 U/ml), patients with chronic aneurysms (90±14 U/ml) and normal controls (91±9 U/ml). In addition, IMA did not change significantly after surgical repair. IMA, at baseline, however, correlated positively with time from symptom onset as well as CRP levels (P=0.05 and P=0.007, respectively). CONCLUSION: IMA is not elevated in AOD when blood sampling is performed within 23±17 hr after symptom onset nor increases after surgery.

Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses.

OBJECTIVE: We sought to investigate the short- and long- term effects of bosentan therapy on endothelial, inflammatory and fibrotic markers in patients with pulmonary arterial hypertension (PAH) and the relation to clinical and hemodynamic responses. METHODS: We studied 16 patients with moderate-severe idiopathic PAH, in WHO functional class II-IV, despite conventional treatment. Patients received additional treatment with bosentan, 62.5 mg twice daily for 1 month, followed by 125 mg twice daily for 11 months. Study endpoints included 6-min walking distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and plasma levels of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), IL-6 and brain natriuretic peptide (BNP). Patients were assessed at baseline, 2 months and 12 months after initiation of bosentan. RESULTS: At 2 months there was an improvement in 6MWD (p < 0.001) and functional class (p < 0.001) and a marked fall in PVR (p < 0.001), ICAM-1 (p < 0.001), IL-6 (p < 0.001)and BNP (p = 0.001). At 12 months, 6MWD was further improved (p < 0.001), PVR remained significantly improved (p < 0.001), mPAP was significantly decreased (p < 0.001) and ICAM-1, IL-6 and BNP remained significantly lower (p < 0.001). Significant correlations were found between changes in ICAM-1 and cardiac index (r = 0.59, p = 0.01), IL-6 and PVR (r = 0.51, p = 0.04), BNP and 6MWD (r = -0.53, p = 0.03) and BNP and PAP (r = 0.51, p = 0.04) between 2- and 12-months treatment. CONCLUSIONS: In patients with moderate-severe PAH, the addition of bosentan to therapy, exerts favorable anti-inflammatory effects, which are associated with clinical and hemodynamic improvement.

Coronary artery perforation in patients undergoing percutaneous coronary intervention: a single-centre report.

The present study reports the incidence, management and clinical outcome of coronary perforations in 5 of 2991 patients (0.1%) undergoing percutaneous coronary intervention, with non-debulking (percutaneous transluminal coronary angioplasty and stent) techniques. There was 1 type I, 1 type II and 3 type III perforations. One perforation was guidewire related, 2 perforations occurred after stent deployment and two occurred during stent-post dilatation with balloons. Restoration was obtained by prolong balloon inflation in three cases. Subsequent cardiac tamponade occurred in 2 patients, requiring pericardiocentesis. One patient died in the cath lab. due to electromechanical dissociation. At follow-up, 3 out of 4 patients were asymptomatic and one had bypass surgery for restenosis. Treatment of coronary perforation requires rapid detection, angiographic classification, and immediate occlusion of perforation site, pericardiocentesis, haemodynamic support and reversal of heparin anticoagulation.

Effect of hormone replacement therapy on inflammatory biomarkers.

Cardiovascular disease is the leading cause of death among women. Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Women present with cardiovascular disease a decade after men and this has been attributed to the protective effect of female ovarian sex hormones. Hormone replacement therapy (HRT), including a variety of estrogen preparations with or without a progestin, has negative effects on most of these soluble inflammatory markers, including E-selectin, cell adhesion molecules, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, inconsistent effects on interleukin-6, and stimulatory effects on vasoprotective cytokine, such as the transforming growth factor-alpha. C-reactive protein, a circulating proinflammatory cytokine produced in both liver and atherosclerotic arteries, increases in response to oral conjugated estrogens but not to transdermal estrogen. Animal and observational studies have shown beneficial effects of hormone therapy in the perimenopausal period or before the development of significant atherosclerosis, whereas randomized trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. This review outlines the effects of HRT on inflammatory biomarkers, summarizes results from observational and randomized trials, and highlights unanswered questions of hormone therapy and cardiovascular risk.

Increased ischaemia modified albumin following coronary artery bypass grafting.

BACKGROUND: Any increase of cardiac biomarkers after coronary artery bypass grafting (CABG) indicates myocyte necrosis and is likely to be related to an impaired outcome. We investigated whether ischaemia-modified albumin (IMA), a biomarker of ischaemia, is also raised following CABG. METHODS: We studied 50 stable consecutive patients undergoing elective isolated CABG on cardiopulmonary bypass, of whom 46 were men and four women, aged 64 +/- 9 years. Blood samples were obtained the day before the operation (pre-op) as well as immediately after the operation, 24 h postoperatively (post-op) and the fourth day post-op and assayed for creatine kinase, the MB isoenzyme of creatine kinase, cardiac troponin-I, albumin and IMA. RESULTS: The typical rising and falling pattern of myocardial necrosis of all three cardiac enzymes was observed post-op (p <0.0001). IMA increased significantly following CABG at all three time points (113 +/- 43, 106.7 +/- 22.6 and 110.2 +/- 12.5 U ml(-1), respectively) compared with pre-op values (91.7 +/- 10.5 U ml(-1)), (p <0.0001); the sample immediately post-op was significantly higher compared with the following samples (immediately post-op vs 24 h, p = 0.008 and immediately post-op vs 4 days, p = 0.03, with no significant difference between the last two). IMA level changes during the study course were independent of the albumin changes. Haemoglobin decreased significantly post-op (p <0.0001 vs baseline) whereas serum creatinine did not differ during the study period. CONCLUSIONS: IMA increases significantly following CABG but whether or not this carries a prognostic significance remains to be elucidated.

Ischemia modified albumin in relation to pharmacologic stress testing in coronary artery disease.

BACKGROUND: Ischemia modified albumin (IMA) is considered a biomarker of myocardial ischemia. We sought to investigate whether IMA plasma levels change during pharmacological stress test, in patients with stable coronary artery disease. METHODS: We studied 37 patients undergoing non-invasive evaluation with a pharmacological stress test, either with radionuclide myocardial perfusion imaging with adenosine or stress echocardiography with dobutamine. Peripheral venous samples were collected before the stress test (baseline), at the end of adenosine infusion or at the peak dose of dobutamine and 60 min after the completion of the stress test for IMA measurement. RESULTS: IMA plasma levels significantly increased at peak vs. baseline (91.28+/-9.59 U/ml vs. 97.97+/-9.69 U/ml, p<0.0001) and subsequently, decreased significantly at 60 min compared to peak (97.97+/-9.69 U/ml vs. 94+/-15.22 U/ml, p=0.016), returning to values similar to those at baseline (p=0.134). Similarly, in patients with a negative stress test, IMA significantly increased at peak compared to baseline (91.08+/-10.03 U/ml vs. 99.58+/-8.43 U/ml, p=0.006) and returned to baseline at 60 min (99.58+/-8.43 U/ml vs. 91.83+/-7.93 U/ml, p=0.019), the 60 minute levels being similar to baseline values (p=0.212). Conversely, in patients with a positive stress test, IMA significantly increased at peak compared to baseline (91.38+/-10.13 U/ml vs. 97.17+/-10.34 U/ml, p=0.006) and although decreased at 1 h, this did not reach statistical significance compared either to the baseline or to the peak values (95.04+/-17.76 U/ml vs. 91.38+/-10.13 U/ml, p=0.315 and 95.04+/-17.76 U/ml vs. 97.17+/-10.34 U/ml, p=0.235, respectively). CONCLUSION: IMA plasma levels change significantly during pharmacologic stress testing, in patients with coronary artery disease, but with no difference between the positive and the negative tests.