Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Less Known but Clinically Relevant Comorbidities of Atrial Fibrillation: A Narrative Review.

BACKGROUND: The important risk factors for atrial fibrillation (AF) in the general population are not always equally important in specific and relatively prevalent diseases. OBJECTIVE: The main goal of this narrative review is to focus attention on the presence and the relationship of AF with several important diseases, such as cancer or sepsis, in order to: 1) stimulate further research in the field, and 2) draw attention to this relationship and search for AF in clinical practice. METHODS: We searched PubMed, SCOPUS, Elsevier, Wiley, Springer, Oxford Journals, Cambridge, SAGE, and Google Scholar for less-known comorbidities of AF. The search was limited to publications in English. No time limits were applied. RESULTS: AF is widely represented in cardiovascular and other important diseases, even in those in which AF is rarely mentioned. In some specific clinical subsets of AF patients (e.g., patients with sepsis or cancer), the general risk factors for AF may not be so important. Patients with new-onset AF have a several-fold increase in relative risk of cancer, deep vein thrombosis, and pulmonary thromboembolism (PTE) during the follow-up. CONCLUSION: AF presence, prognosis, and optimal therapeutic approach are insufficiently recognised in several prevalent diseases, including life-threatening ones. There is a need for a better search for AF in PTE, pulmonary oedema, aortic dissection, sepsis, cancer and several gastrointestinal diseases. Improved AF detection would influence treatment and improve outcomes.

Association of stress hyperglycemia and atrial fibrillation in myocardial infarction.

BACKGROUND: Stress hyperglycemia has an untoward effect on prognosis in acute myocardial infarction (AMI). Evidence on the interrelationship between stress hyperglycemia and atrial fibrillation (AF) in AMI is sparse. We hypothesized that stress hyperglycemia and AF, both being markers of worse in-hospital prognosis, may be interrelated and we therefore analyzed the relationship between stress hyperglycemia and AF in AMI. PATIENTS AND METHODS: The study was a retrospective analysis of 543 patients with AMI. The average age was 63.8 +/- 10.6 years and 54.9% were male. RESULTS: AF was more prevalent in 200 AMI patients with admission glucose >or= 8.0 mmol/l (15.00%) than in 343 patients with admission glucose < 8 mmol/l (7.87%), Pearson's chi-squared P = 0.010, OR 2.07 (95% CI 1.180-3.637). In AMI patients with neither stress hyperglycemia nor AF, in-hospital mortality was 1.67%; in patients with stress hyperglycemia without AF, the mortality was 3.85%. In patients with AF without stress hyperglycemia, mortality was high at 13.04%, and in patients with both stress hyperglycemia and AF it was extremely high at 24.14%. Hyperglycemia (r = 0.1680, P = 0.0472) but not AF correlated with the size of the AMI. Compared with an AF prevalence of 8.28% in the normoglycemic group, AF was found more often (14.65%) in a group with diabetes mellitus (DM), Pearson's chi-squared P = 0.02, OR = 2.04 (95% CI 1.06-3.93). There was no significant difference in the occurrence of AF between patients with previously diagnosed DM and those with new-onset DM (Fisher's exact test P = 0.34). CONCLUSIONS: Stress hyperglycemia is associated with increased prevalence of AF in AMI. Patients with both stress hyperglycemia at admission (>or= 8.0 mmol/l) and AF had almost 14.5 times higher in-hospital mortality than patients who had neither stress hyperglycemia nor AF. Stress hyperglycemia was an independent predictor of the in-hospital mortality in multivariate regression analysis, but AF was not.

Heart failure caused by cardiac rhabdomyosarcoma.

Rhabdomyosarcoma accounts for 20% of primary malignant cardiac tumours. We describe a woman with cardiac rhabdomyosarcoma. She had loss of appetite, loss of weight, and symptoms of heart failure. A mobile tumour in the left atrium, entering the left ventricle during diastole, was detected by transthoracic echocardiography. The tumour was removed surgically in total; histological diagnosis was rhabdomyosarcoma; however, the patient died after 6 months. In conclusion, primary malignant cardiac tumours can simulate heart failure or systemic disorders. Cardiac rhabdomyosarcomas have a poor prognosis with average survival of 6 months after diagnosis.

A successful retrieval of stripped outer coating of J-tip diagnostic guidewire from the left popliteal artery during elective coronary angiography.

INTRODUCTION: Entrapment and fracture of diagnostic or therapeutic devices within the coronary circulatory system are a rare, but increasing problem. CASE REPORT: A 70-year-old man was admitted in our clinic for coronary angiography before the planned aortic valve replacement. An arterial sheath was inserted in the right common femoral artery. After introducing a J-tip diagnostic coronary guidewire into the aorta and advancing a left Judkins diagnostic catheter over it, suddenly occured peeling off of the wire's hydrophilic coating at the aortic arch level. Very soon, this outer coating of guidewire carried by the blood stream was entered into the left femoral artery, then into the left popliteal artery. This stripped part of guidewire was successfully caught and extracted out by using a goose-neck snare catheter. CONCLUSION: A sudden stripping of outer coating of a J-tip diagnostic hydrophilic coronary guidewire during coronary angiography is possible to manage quickly and successfully by the use of a simple cathether.

Stress hyperglycemia in acute ST-segment elevation myocardial infarction is a marker of left ventricular remodeling.

INTRODUCTION: Stress hyperglycemia (SH) in STEMI is associated with high risk of in-hospital mortality. It is still controversial if SH is marker of high post-hospital risk. OBJECTIVES: The aim was to analyze in-hospital and one-year risk associated with SH in STEMI and to study if SH is marker of LV remodeling. METHODS: We enrolled 275 patients who were admitted with first STEMI and reperfused. Patients were divided according to admission glycemia in three groups: (1) with diabetes mellitus (DM); (2) with SH, without DM and; (3) without both DM and SH. SH was defined as admission blood glucose level ≥ 8 mmol/l. RESULTS: In-hospital mortality was higher in patients with known DM (5%) and highest in patients with SH without previous DM (9.3%), and only 1.6% in the third group, P < 0.05. In patients without known DM, SH was associated with 6.378-fold higher in-hospital mortality. Total mortality was double in group with SH without DM compared to the third group (13.9% versus 6.3%). EDV changed in patients with SH without DM from 126 ± 37 to 145 ± 30 ml after one year, P < 0.05. CONCLUSION: SH is associated with high in-hospital mortality risk and it could be marker of LV remodeling (significant increase of EDV during one year).

Life-saving percutaneous coronary interventions on the unprotected left main coronary artery in patients with acute coronary syndrome in the catheterization laboratory without cardiosurgical back-up.

INTRODUCTION: The optimal revascularization strategy for unprotected left main coronary disease (ULMCD) is the subject of ongoing debate and patients with ULMCD still represent a challenge for interventionalist, especially in the setting of an acute coronary syndome (ACS). CASE REPORT: We presented two cases of percutaneous treatment of ULMCD in the settings of ACS (ST Segment Myocardial Infarction and Non ST Segment Myocardial Infarction--STEMI and NSTEMI) in a catheterization laboratory without back-up of cardiosurgical department. Both patients were hemodynamically unstable with clinical signs of cardiogenic shock. Coronary angiography revealed left main thromobosis and using intra-aortic balloon pump as hemodynamic support primary angioplasty procedures were performed. Immediately after the procedures the patients hemodynamically improved and remained stable till discharge from hospital. CONCLUSION: Percutaneous coronary intervention (PCI) has become the most common strategy of revascularization in ACS patients with ULMCD and is generally preferred in patients with multiple comorbidities and/or in very unstable patients. In cases with no cardiosurgical departments PCI is an inevitable, bail-out, life saving procedure.

[Vasospastic angina pectoris complicated by acute myocardial infarction and complete atrioventricular block].

BACKGROUND: A prolonged coronary artery spasm with interruption of coronary blood flow can lead to myocardial necrosis and increase of cardiospecific enzymes and can be complicated with cardiac rhythm disturbances, syncopc, or even sudden cardiac death. CASE REPORT: A 55-year old male felt a severe retrosternal pain when exposing himself to cold weather. The pain lasted for 20 minutes and was followed by the loss of conscience. Electrocardiogram (ECG) showed a complete antrioventricular (AV) block with nodal rhythm and marked elevation of ST segment in inferior leads. Electrocardiogram was soon normalized, but serum activities of cardiospecific enzymes were increased. Coronarography showed normal findings for the left coronary artery and a narrowing at the middle part of the right coronary artery, which disappeared after intracoronary application of nitroglycerine. The following therapy was prescribed: Diltiazem, Amlodipin, Isosorbid mononitrate, Molisdomin, Atrovastatin, Aspirin and Nitroglycerine spray. After 7 months medicaments were abandoned and the patient experienced again reccurent chest pain episodes at rest. Transitory ST segment elevation was recorded in inferior leads of ECG, but without increase of cardiospecific enzymes serum activities. After restoration of the medicament therapy anginal episodes ceased. CONCLUSION: Coronary dilators in maximal doses can prevent attacks of vasospastic angina.

[Ebstein's anomaly as a cause of paroxysmal atrial fibrillation].

BACKGROUND: Ebstein's anomaly is characterized by a displacement of the tricuspid valve toward apex, because of anomalous attachment of the tricuspid leaflets. There are type B of Wolff-Parkinson-White (WPW) syndrome and paroxysmal arrhythmias in more than a half of all patients. CASE REPORT: We presented a female, 32-year old, with frequent paroxysms of atrial fibrillation. After conversion of rhythm an ECG showed WPW syndrome. Echocardiographic examination discovered normal size of the left cardiac chambers with paradoxical ventricular septal motion. The right ventricle was very small because of its atrialization. The origin of the tricuspid valve was 20 mm closer to apex of the right ventricle than the origin of the mitral valve. Electrophysiological examination showed a posterolateral right accesorial pathway. Atrial fibrillation was induced very easily in electrophysiological laboratory and a successful ablation of accessorial pathway was made. There were no WPW syndrome and paroxysms of atrial fibrillation after that. CONCLUSION: Ebstein's anomaly is one of the reasons of paroxysmal atrial fibrillation, especially in young persons with WPW syndrome.

[Cardiac rhabdomyosarcoma].

BACKGROUND: Primary malignant cardiac tumors are rare entities and rhabdomyosarcoma accounts 20% of these lesions. CASE REPORT: We presented a female patient with loss of appetite and loss of weight. She also had symptoms of heart failure and bilateral pleural effusions. A mobile tumor in the left heart with the entrance from the left atrium to left ventricle during diastole was seen by transthoracic echocardiography. The tumor was extirpated in total, histologic diagnosis was rhabdomyosarcoma, and the patient died after 6 months. CONCLUSION: Primary malignant cardiac tumors can simulate heart failure or systemic disorders. Cardiac rhabdomyosarcomas have a poor prognosis with the average survival of 6 months after the occurrence of symptoms and making a diagnosis. In cardiac insufficiency, differential diagnostics should be used to consider cardiac tumors that could be with certainty confirmed or excluded by echocardiography.

[Influence of the double antiplatelet therapy on patency of the occluded artery after acute myocardial infarction with ST-segment elevation].

BACKGROUND/AIM: Most patients with acute myocardial infarction with ST-segment elevation (STEMI) are still treated with pharmacological reperfusion, which is not always successful. That is the reason for searching possibilities for a better success of reperfusion with adding new antiplatelet drugs. The aim of this study was to investigate weather addition of clopidogrel as a second antiplatelet drug, improves the patency of the infarct-related artery after STEMI. METHODS: We prospectively enrolled 65 patients, 29-72 years old, hospitalized due to the first STEMI within 6 hours after the on-set of a chest pain. They were treated with a fibrinolytic agent (streptokinase or tissue plasminogen activator--tPA), aspirin, and low molecular heparin (enoxaparin). A group of 50 patients, beside this therapy, received clopidogrel. Coronary angiography was performed between 5th and 10th day of hospitalization to assess for late patency of the infarct-related artery. Infarct-related artery was considered as patent if thrombolysis in myocardial infarction (TIMI) flow grade was 2 or 3, and as occluded if TIMI flow grade was 0 or 1. RESULTS: In the group of patients who received double antiplatelet therapy (aspirin and clopidogrel), infarct-related artery was occluded in 3 cases (6%); in the group of patients without clopidogrel, infarct-related artery was occluded in 4 patients (26.7%),p < 0.05. There were less frequency of postinfarction angina (6% vs 13.3%), and rarer necessity for rescue percutaneous coronary intervention (4% vs. 13.3%) in the first group, but without statistical significance. CONCLUSION: Adding of clopidogrel to the standard reperfusion pharmacotherapy, as a second antiplatelet drug, increases the number of patients with patent infarct-related artery and the success of reperfusion.