Long-Term Outcome of Acute Coronary Syndromes in Patients on Chronic Oral Anticoagulants: Data from the EPICOR Study.

OBJECTIVE: To analyze characteristics, management and outcomes of patients with acute coronary syndromes (ACS) receiving chronic oral anticoagulant (OAC) therapy enrolled in the EPICOR (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients) prospective, international, observational study of antithrombotic management patterns in ACS survivors (NCT01171404). METHODS: This post-hoc analysis evaluated the association between OAC use at baseline (OACb) and time from hospital admission to percutaneous coronary intervention (PCI) (tHA-PCI), pre-PCI thrombolysis in myocardial infarction (TIMI) 3 flow, stent type, length of hospitalization, and clinical endpoints; death, non-fatal MI, and non-fatal stroke, a composite of these ± bleeding, over 2 years' followup. RESULTS: Of 10,568 ACS patients, 345 (3.3%) were on OACb (non-ST-segment elevation ACS [NSTEACS], n=268; ST-segment elevation MI [STEMI], n=77). OACb patients were older with more comorbidities. In NSTE-ACS OACb patients, tHA-PCI was longer (median 57.4 vs. 27.8 h; p=.008), and TIMI 3 flow rarer (26.0 vs. 33.5%; p=0.035). OACb patients had longer mean hospital stay (NSTEACS: 8.9 vs. 7.6 days; p<0.001; STEMI: 9.5 vs. 7.8 days; p=0.015), and higher rates of the composite endpoint (NSTE-ACS: 16.8 vs. 8.8%; p<0.0001; STEMI: 23.4 vs. 5.9%; p<0.0001). Bleeding events were more common with OACb (NSTE-ACS: 6.0 vs. 3.3%; p=0.01; STEMI: 6.5 vs. 2.8%; p=0.04). CONCLUSION: At 2-years, OACb use was associated with an increased risk of cardiovascular and bleeding events in STEMI and NSTE-ACS. NSTE-ACS patients on OACb experienced prolonged time to intervention, lower rates of TIMI 3 flow and longer hospitalization.

Management of bleeding in patients hospitalized in the intensive cardiac care unit: expert opinion of the Association of Intensive Cardiac Care and Section of Cardiovascular Pharmacotherapy of the Polish Cardiac Society in cooperation with specialists in other fields of medicine.

Nowadays, the intensive cardiac care unit (ICCU) provides care for patients with acute coronary syndrome, acute and exacerbated chronic heart failure, cardiogenic shock, sudden cardiac arrest, electrical storm, as well as with indications for urgent cardiac surgical treatment. Most of these patients require the use of 1, 2, or frequently even 3 drugs that act on the blood coagulation pathway. While antithrombotic drugs prevent thromboembolic events, they are associated with a higher risk of bleeding. In this population of patients, bleeding may often have a worse impact on prognosis than the primary disease. In this expert opinion of the Association of Intensive Cardiac Care, we presented practical guidelines on the management of bleeding in patients hospitalized at the ICCU, including bleeding risk reduction and treatment recommendations. Because of multiple comorbidities and diverse organs that may be the source of bleeding, we provided also recommendations from specialists in other fields of medicine. We hope that this document will facilitate the management of one of the most challenging populations at the ICCU.

PPARG2 Pro12Ala and TNFα -308G>A Polymorphisms Are Not Associated with Heart Failure Development in Patients with Ischemic Heart Disease after Coronary Artery Bypass Grafting.

TNFα and PPARγ are important modulators of metabolism, inflammation, and atherosclerosis. Coronary artery disease is the leading cause of heart failure (HF). The aim of the study was to assess whether polymorphisms of the TNFα (-308G>A) and PPARG2 (Pro12Ala) genes are associated with the risk of developing HF by patients with ischemic heart disease. Methods. 122 patients without HF (aged 63 ± 8.8 years, 85% males) with confirmed coronary artery disease qualified for coronary bypass grafting were enrolled in the study. After the procedure, they were screened for cardiac parameters. Those with elevated NT-proBNP or diminished left ventricular ejection fraction during follow-up were assigned to the HF group (n=78), and the remaining ones to the non-HF group (n=44). The TNFα -308G>A and PPARG2 Pro12Ala polymorphisms were detected using the TaqMan method. Results. The distributions of TNFα -308G>A and PPARG2 Pro12Ala did not differ between the HF and non-HF groups (-308G>A: 16% vs. 11.4% of alleles; Pro12Ala: 23.9% vs. 20.5% of alleles, respectively). IL-6 concentration in the plasma of TNFα A-allele carriers at months 1 and 12 after CABG was higher in the HF group compared to the non-HF group (1 month after CABG: 5.3 ± 3.4 vs. 3.1 ± 2.9, p<0.05; 12 months after CABG: 4.2 ± 3,9 vs. 1.4 ± 1.2, p<0.01, respectively). Both polymorphisms were not related to changes in the plasma TNFα concentration or other parameters related to HF. Conclusions. Our study did not reveal any correlation between the PPARG2 Pro12Ala and TNFα -308G>A polymorphisms and development of HF in patients with ischemic heart disease after coronary bypass grafting.

Severe Course of Peripartum Cardiomyopathy and Subsequent Recovery in a Patient with a Novel TTN Gene-Truncating Mutation.

BACKGROUND Peripartum cardiomyopathy (PPCM) is a potentially life-threatening, pregnancy-associated cause of heart failure affecting previously healthy women. Recent research suggests a possible role of 16-kDa prolactin in promoting cardiomyocyte damage. However, the genetic predisposition is not well recognized. CASE REPORT We report the case of a 25-year-old woman with a severe course of PPCM with left ventricle ejection fraction of 25-30%, complicated by ventricular arrhythmia and postpartum thyroiditis. As no traditional risk factors of PPCM were identified, the patient was referred for genetic testing. Next-generation sequencing revealed a novel titin gene-truncating mutation NM_001267550: p.Leu23499fs/c.70497_40498insT in the proband as well as in her mother. In the patient, a very late recovery >12 months postpartum was observed, which required long-term medical treatment with bromocriptine. CONCLUSIONS PPCM may occur in women with the genetic predisposition, being modified by an interaction of biological factors, such as a high prolactin level, a ventricular arrhythmia, and an autoimmune disorder. Recovery from severe heart failure due to an inherited cardiomyopathy is possible with careful and appropriate medical management.

Myocardial Expression of PPARγ and Exercise Capacity in Patients after Coronary Artery Bypass Surgery.

Activation of PPARs may be involved in the development of heart failure (HF). We evaluated the relationship between expression of PPARγ in the myocardium during coronary artery bypass grafting (CABG) and exercise tolerance initially and during follow-up. 6-minute walking test was performed before CABG, after 1, 12, 24 months. Patients were divided into two groups (HF and non-HF) based on left ventricular ejection fraction and plasma proBNP level. After CABG, 67% of patients developed HF. The mean distance 1 month after CABG in HF was 397 ± 85 m versus 420 ± 93 m in non-HF. PPARγ mRNA expression was similar in both HF and non-HF groups. 6MWT distance 1 month after CABG was inversely correlated with PPARγ level only in HF group. Higher PPARγ expression was related to smaller LVEF change between 1 month and 1 year (R = 0.18, p < 0.05), especially in patients with HF. Higher initial levels of IL-6 in HF patients were correlated with longer distance in 6MWT one month after surgery and lower PPARγ expression. PPARγ expression is not related to LVEF before CABG and higher PPARγ expression in the myocardium of patients who are developing HF following CABG may have some protecting effect.

Serum beta-2 microglobulin levels for predicting acute kidney injury complicating aortic valve replacement.

OBJECTIVES: Acute kidney injury complicating both transcatheter and surgical aortic valve replacement is associated with high rates of morbidity and mortality. The aim of this study was to investigate the role of serum beta 2 (ß2) microglobulin, cystatin C and neutrophil gelatinase-associated lipocalin levels in detecting periprocedural acute kidney injury. METHODS: Eighty consecutive patients who were 70 years of age or older and who were having surgical (n = 40) or transcatheter (n = 40) aortic valve replacement were recruited in a prospective study. The biomarkers were tested before the procedure, 6 times afterwards, at discharge and at a 6-month follow-up visit. RESULTS: The baseline ß2-microglobulin level was the strongest predictor of acute kidney injury as a complication of transcatheter aortic valve replacement [odds ratio (OR) 5.277, P = 0.009]. Its level 24 h after the procedure reached the largest area under the curve (AUC) of 0.880 (P < 0.001) for detecting acute kidney injury. In multivariate logistic regression analysis, the levels of ß2-microglobulin and cystatin C 24 h after the procedure were significantly associated with acute kidney injury after transcatheter valve replacement (OR 38.15, P = 0.044; OR 1782, P = 0.019, respectively). In the surgical aortic valve replacement group, the highest AUCs belonged to ß2-microglobulin and cystatin C at 24 h (AUC = 0.808, P = 0.003 and AUC = 0.854, P = 0.001, respectively). Their higher values were also associated with acute kidney injury (OR 17.2, P = 0.018; OR 965.6, P = 0.02, respectively). A persistent increase in the postoperative levels of ß2-microglobulin following acute kidney injury was associated with the progression of chronic kidney disease for 6 months after both transcatheter (OR 6.56, P = 0.030) and surgical (OR 7.67, P = 0.03) aortic valve replacements. CONCLUSIONS: Serum ß2-microglobulin had the potential to predict acute kidney injury complicating transcatheter valve replacement and to diagnose it as early as 24 h after both the transcatheter and the surgical procedures. Furthermore, the serum level of ß2-microglobulin was indicative of the progression of chronic kidney disease.

Current patterns of antithrombotic and revascularisation therapy in patients hospitalised for acute coronary syndromes. Data from the Polish subset of the EPICOR study.

BACKGROUND: Cardiovascular disease is the leading cause of mortality and morbidity in developed countries, including Poland. Antithrom-botic drugs play a crucial role in the management of acute coronary syndromes (ACS). Recent clinical trials have demonstrated the efficacy and safety profiles of new antiplatelet and anticoagulant agents, which may be used as add-on therapy or replacements for older drugs. The long-t E: rm follow-u P: of antithrombotic management patterns I: n acute COR: onary syndrome patients (EPICOR) is a prospective international observational study (NCT01171404) designed to describe the use of antithrombotic management strategies for the treatment of ACS during the acute phase and over a follow-up period of up to two years from the index event. A total of 608 patients from 26 hospitals in Poland were enrolled into the registry between September 2010 and March 2011. AIM: The aim of this work was to summarise data on pre-hospital and in-hospital and revascularisation therapy in 608 patients enrolled into the registry in Poland. METHODS: The registry collected the records of patients who were hospitalised for ACS within 24 h of symptom onset and who had a final diagnosis of unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI), and survived to discharge. RESULTS: Among 608 enrolled patients, 291 had a final diagnosis of STEMI and 317 had a final diagnosis of NSTEMI/UA. Patients with NSTEMI/UA were generally at higher cardiovascular risk than patients with STEMI. Before admission to the hospital antiplatelet drugs (acetylsalicylic acid [ASA] and/or clopidogrel) were administered more frequently to STEMI than to NSTEMI/UA patients. Glycoprotein (GP) IIb/IIIa inhibitors were used in almost half of the STEMI patients and in nearly 10% of NSTEMI/UA patients. The combinations of antiplatelet drugs included ASA + clopidogrel (predominantly in NSTEMI/UA) or ASA + clopidogrel + GPIIb/IIIa inhibitor (predominantly in STEMI), while other possible combinations were not used. Almost all STEMI patients (96.2%) and the clear majority of NSTEMI/UA patients (73.8%) were subjected to percutaneous coronary intervention (PCI), while coronary artery bypass grafting was performed in only 2.5% of the NSTEMI/UA patients. At the time of discharge from hospital almost all patients with STEMI received ASA together with clopidogrel, but this strategy was used only in 91.5% of patients with NSTEMI/UA (p < 0.05). Unfractionated heparin was used in 62% of patients, low-molecular weight heparin in 35%, fondaparinux in 0.7%, and bivalirudin in none of the studied patients. CONCLUSIONS: Among patients with ACS enrolled to the EPICOR study in Poland, antiplatelet therapy was started in the pre-hospital phase in approximately one-third of the STEMI patients and in one out of ten of the NSTEMI/UA patients. The initial antiplatelet therapy was mostly based on ASA + clopidogrel and was followed by a combination of ASA + clopidogrel + GPIIb/IIIa inhibitor. Other drugs or combinations, as well as novel antiplatelet drugs, were only used exceptionally. Almost 10% of NSTEMI/UA patients did not receive dual antiplatelet therapy at discharge. PCI plays a dominating role in the first-line treatment for the patients enrolled to this registry in Poland.

PPAR Gamma Expression Levels during Development of Heart Failure in Patients with Coronary Artery Disease after Coronary Artery Bypass-Grafting.

Genetic research has elucidated molecular mechanisms of heart failure (HF). Peroxisome proliferator-activated receptors (PPARs) seem to be important in etiology of HF. The aim of study was to find the correlation between PPARγ expression during development of HF in patients and coronary artery disease (CAD) after coronary artery bypass-grafting (CABG). Methods and Results. We followed up 157 patients (mean age 63) with CAD without clinical, laboratory, or echo parameters of HF who underwent CABG. Clinical and laboratory status were assessed before CABG and at 1, 12, and 24 months. During CABG slices of aorta (Ao) and LV were collected for genetic research. HF was defined as LVEF <40% or NT-proBNP >400 pg/mL or 6MWT <400 m. Patients were divided into 2 groups: with and without HF. PPARγ expression in Ao and LV was not increased in both groups at 2-year follow-up. Sensitivity of PPARγ expression in Ao above 1.1075 in detection of HF was 20.5% (AUC 0.531, 95% CI 0.442-0.619). Positive predictive value (Ppv) was 85.7%. Sensitivity and specificity of PPARγ expression in the LV in detection of HF were 58% and 92.9%, respectively (AUC 0.540, 95% CI 0.452-0.626). Ppv was 73.2%. Conclusion. PPARγ expression in Ao and LV was comparable and should not be used as predictive factor for development of HF in patients with CAD after CABG.

Early implementation of continuous venovenous haemodiafiltration improves outcome in patients with heart failure complicated by acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a serious complication of heart failure (HF). Continuous venovenous haemodiafiltration (CVVHDF) is a widely accepted method for treating this complication. However, the optimal time of its initiation has not been established. AIM: To compare the outcome of patients with HF treated with CVVHDF which was implemented late (the first two years of our experience) or early (the next two years of our experience). METHODS: Thirty seven patients, mean age 65 years, were hospitalised between April 2006 and January 2010 with the diagnosis of HF complicated by AKI. The primary cardiovascular diseases were: valvular heart disease (30%), acute coronary syndrome (27%), dilated cardiomyopathy (16%), exacerbation of chronic HF (11%), and others (16%). The inclusion criteria for CVVHDF therapy were: symptoms of HF including cardiogenic shock with high levels of creatinine (≥ 300 µmol/L) and/or oliguria and/or symptoms of septic shock. The exclusion criteria were: serious coagulation disturbances or inability of placing a catheter in a central vein. Group A consisted of 12 patients treated from April 2006 to the end of 2007. In group B, there were 25 patients treated from the beginning of 2008 to January 2010. Before treatment, mean ejection fraction, left ventricular diastolic diameter and mean blood pressure in both groups were comparable. Renal replacement therapy in group B was started earlier than in group A (mean 2.0 ± 2.0 days vs 4.0 ± 4.3 days from the onset of symptoms of AKI; NS). RESULTS: The day after the beginning of CVVHDF, renal failure parameters improved in both groups, but the improvement was much more significant in group B. In group A, 11 (92%) patients died. The mean CVVHDF duration was six days and all patients required mechanical ventilation. In group B, 17 (68%) patients died (NS). The mean CVVHDF duration was shortened to four days. Seventeen (68%) patients were ventilated mechanically and this parameter was significantly different between the groups (p = 0.03) CONCLUSIONS: An early introduction of CVVHDF significantly diminished the need to use mechanical ventilation and indicated a positive trend in the reduction of in-hospital mortality in patients with HF complicated by AKI.

Circadian variations of interleukin 6 in coronary circulations of patients with myocardial infarction.

UNLABELLED: We hypothesize that higher morbidity of patients with ST-segment elevation myocardial infarction (STEMI) in the out-of-office hours differences in outcome after myocardial infarction may depend on the concentrations of inflammatory cytokines. The aim of the study was to determine the relation between the time of percutaneous coronary intervention (PCI) and local concentration of interleukin 6 (IL-6) and its soluble receptors (sIL-6R and sgp130) in patients with STEMI. METHODS AND RESULTS: The study included 32 patients with invasively treated left anterior descending artery occlusion and no significant co-morbidities. Blood samples were drawn from coronary sinus and aorta before and after intervention. Patients admitted in the afternoon (13-20) presented significantly higher mean IL-6 levels in all samples than patients admitted in the morning. There was a positive correlation between time of intervention and concentrations of IL-6 in all samplings, but also with transcardiac IL-6 gradient at the end of procedure and IL-6 increase during PCI. We did not find any significant association between time of PCI and concentrations of sIL-6R and sgp130, time from pain to balloon, angiographic parameters or medical history. CONCLUSIONS: Coronary concentration of IL-6 in patients with STEMI is significantly higher in the afternoon than in the morning. This might be involved in increased morbidity of those patients.

Percutaneous coronary interventions affect concentrations of interleukin 6 and its soluble receptors in coronary sinus blood in patients with stable angina.

Coronary stenting may create local inflammatory reaction. Interleukin 6 effects depend on the presence of soluble receptors (sIL-6R and sgp130) that facilitate or impede interleukin 6 signal transduction. Concentrations of interleukin 6 and its soluble receptors were assessed in aorta and coronary sinus after stenting in optimally treated stable angina patients scheduled for elective stenting. Baseline levels of interleukin 6 and its soluble receptors in patients did not differ from healthy controls. Initial levels of sIL-6R in aorta were significantly higher than in coronary sinus but this difference disappeared after intervention. Stenting caused interleukin 6 concentration increase to a similar extent both in coronary sinus and in aorta. Moreover, there was significantly higher sgp130 concentration in coronary sinus than in aorta. Coronary intervention increases concentration of interleukin 6 in patients with stable angina. It affects the cardiac level of interleukin 6 soluble receptors what may influence the local inflammatory reaction.

Coronary sinus concentrations of interleukin 6 and its soluble receptors are affected by reperfusion and may portend complications in patients with myocardial infarction.

UNLABELLED: Interleukin 6 (IL-6) is a pleiotropic cytokine involved in both inflammatory reaction and myocardial response to stress. Its effects largely depend on the concentration of the soluble receptors (sIL-6R and sgp130). We investigated the production of IL-6, sIL-6R and sgp130 by the heart during ischemia and reperfusion. METHODS: The levels of IL-6 were determined in blood of 34 patients with first myocardial infarction (STEMI), left anterior descending (LAD) artery occlusion, otherwise normal coronaries, without significant co-morbidities and 16 comparable subjects with stable ischemic heart disease and lesion in LAD. Blood samples from coronary sinus (CS) and aorta (Ao) were drawn before percutaneous intervention (PCI), immediately after and at the end of the procedure. Venous blood from 30 healthy volunteers served as control. RESULTS: STEMI patients presented high IL-6 concentrations that increased further after reperfusion when its levels in CS became significantly higher than in Ao. In both groups prior to the PCI there were significantly higher concentrations of sIL-6R in Ao than in CS. This difference disappeared immediately after reperfusion. STEMI patients who experienced cardiovascular complications had higher IL-6 concentration and higher transcardiac sIL-6R gradient than patients with event-free hospitalisation. This association was confirmed in multivariate logistic regression analysis. Myocardial infarction increases concentration of IL-6 that is further elevated by reperfusion. A transcardiac gradient of sIL-6R during ischemia may indicate that large amounts of soluble IL-6 receptors are bound to the infarcted heart and thus affect signal transduction. IL-6 and initial sIL-6R gradient may portend complications in STEMI patients.

Persistent atrial fibrillation as a prognostic factor of outcome in patients with advanced heart failure.

INTRODUCTION: Chronic heart failure (CHF) is associated with high morbidity and mortality and is diagnosed more and more frequently. Fifteen to 30% of patients with systolic CHF develop atrial fibrillation (AF). AIM: To establish whether persistent AF was an independent predictor of mortality, and had a predictive value with respect to late clinical outcomes in patients with systolic CHF. METHODS: Analysis comprised 120 men with systolic CHF. In 35 (58%) patients CHF was the result of ischaemic heart disease and in 25 (42%)--idiopathic dilated cardiomyopathy (DCM). Presence or absence of AF was a criterion of patients' subsequent division into two subgroups. Sixty patients with AF were assigned to the AF group. The control group involved 60 individuals with CHF and sinus rhythm (SR) on enrollment. Mean follow-up time was 36 months. RESULTS: Overall 59 (49%) patients died during 3-year follow-up, including 33 (56%) in the AF group. Deaths were noted more often in CHF patients with underlying ischaemic heart disease than DCM (66% vs 34%). This difference reached statistical significance in the AF group (72% vs 28%, p<0.001). Moreover, patients with AF more often complained of palpitations (p<0.01), had worse exercise capacity (p<0.01) as well as more frequently presented complex ventricular arrhythmia (p<0.01). The rate of hospital readmission was also higher (p<0.02). In univariate as well as multivariate analysis, AF was not found to be an independent predictor of mortality. Factors with a potential impact on adverse prognosis were concomitant complex ventricular arrhythmias (p=0.01), diabetes (0.04) and reduced exercise capacity (p<0.01). CONCLUSIONS: Persistent AF is not an independent risk factor of death in patients with advanced systolic CHF. However, it has an unfavourable impact on functional status. Concomitant complex ventricular arrhythmias and reduced exercise capacity worsen prognosis in this group of patients.