Dejan Simeunovic

Renal effects of ularitide in patients with decompensated heart failure

BACKGROUND Renal function frequently deteriorates in decompensated heart failure (DHF) patients, and one determinant is reduced renal blood flow. This may, in part, result from low cardiac output (CO), reduced mean arterial pressure (MAP), and venous congestion. The combined impact of both venous congestion (elevated right atrial pressure [RAP]) and low MAP are reflected by a reduced pressure gradient MAP-RAP. This study investigated the renal effects of ularitide, a synthetic version of the renal natriuretic peptide urodilatin in DHF patients. METHODS In SIRIUS II, a double-blind phase II trial, 221 patients hospitalized for DHF (with dyspnea at rest or minimal activity, cardiac index <or=2.5 L/min per square meter, and pulmonary artery wedge pressure >or=18 mm Hg) were randomized to a single 24-hour infusion of ularitide (7.5, 15, or 30 ng/kg per minute) or placebo added to standard therapy. RESULTS Estimated glomerular filtration rate, serum creatinine, creatinine clearance, and blood urea nitrogen (BUN) were not impaired by ularitide throughout infusion and during a 2-day follow-up period. At 24 hours, 15 ng/kg per minute ularitide reduced BUN levels (-4.07 +/- 12.30 vs -0.20 +/- 7.50 for placebo, P < .05). Ularitide at 15 and 30 ng/kg per minute rapidly elevated CO with sustained effects. Although 15 ng/kg per minute ularitide preserved the pressure gradient MAP-RAP, 30 ng/kg per minute ularitide reduced MAP-RAP by -7.8 +/- 10.6 mm Hg vs -2.4 +/- 9.8 mm Hg for placebo (P < .01, at 6 hours). A strong inverse correlation between MAP-RAP and BUN levels (Corr = -0.50579, P = .00015) was observed with 15 ng/kg per minute ularitide. CONCLUSIONS Single 24-hour infusions of ularitide at 15 ng/kg per minute preserved short-term renal function in DHF patients possibly by both elevating CO and maintaining the MAP-RAP pressure gradient.

Management strategies in pericardial emergencies

Background:The most frequent pericardial emergency is cardiac tamponade, but complications of an acute coronary syndrome and aortic dissection may also involve the pericardium. Acute pericarditis can also represent a medical emergency due to chest pain of upsetting intensity. Decompensations in chronic advanced constriction and in the clinical course of purulent pericarditis necessitate critical care as well.Diagnosis and Management:The diagnosis of cardiac tamponade is based on clinical presentation and physical findings, confirmed by echocardiography and cardiac catheterization. Tamponade is an absolute indication for urgent drainage, either by pericardiocentesis or surgical pericardiotomy. The approach for pericardiocentesis can be subxiphoid or intercostal using echocardiographic or fluoroscopic guidance. Urgent drainage, combined with intravenous antibiotics, is also mandatory in suspected purulent pericarditis. If confirmed, it should be combined with intrapericardial rinsing (best by a surgical drainage). Pericardiocentesis is contraindicated in cardiac tamponade complicating aortic dissection. This condition should immediately lead to cardiac surgery. Although pericardiectomy is the only treatment for permanent constriction, this procedure is contraindicated when extensive myocardial fibrosis and/or atrophy are demonstrated.Case Study:Iatrogenic tamponade may occur during percutaneous mitral valvuloplasty, implantation of pacemakers, electrophysiology and radiofrequency ablation procedures, right ventricular endomyocardial biopsy, percutaneous coronary interventions, and rarely during Swan-Ganz catheterization. The authors report on a 79-year-old who suffered coronary perforation and cardiac tamponade during elective stent implantation. Tamponade was successfully treated with pericardiocentesis and implantation of a membrane-covered graft stent. Subsequent recurrent pericarditis/postpericardial injury syndrome with moderate pericardial effusion was initially treated with aspirin and then with aspirin and colchicine. At 6 months, the patient is in stable remission even after withdrawal of colchicine.Conclusion:Natural history of pericardial diseases can be complicated with pericardial emergencies requiring prompt diagnosis, intensive care with hemodynamic monitoring, and early aggressive management. Medical supportive measures, drainage of pericardial effusion, surgical pericardiotomy, and pericardiectomy should be applied when needed with no delay. This procedural approach also applies to iatrogenic interventions leading to tamponade.ZusammenfassungHintergrund:Der häufigste Notfall bei Perikarderkrankungen ist die Herzbeuteltamponade. Komplikationen bei akutem Koronarsyndrom oder einer Aortendissektion können ebenfalls das Perikard betreffen. Dies gilt auch für die Exazerbation präkordialer Beschwerden einer akuten Perikarditis, die Dekompensation bei chronisch-konstriktiver Perikarditis oder bei einer purulenten Perikarditis.Diagnose und Management:Die Diagnose der Herzbeuteltamponade stützt sich auf Symptome, klinische Untersuchung, die Ergebnisse der Echokardiographie und ggf. einer Herzkatheteruntersuchung. Bei einer Tamponade ist die umgehende Entlastung eine lebensrettende Indikation zu Perikardpunktion oder chirurgischer Perikardiotomie. Die Perikardpunktion kann von subxiphoidal oder interkostal unter Röntgen- oder Echokardiographiekontrolle erfolgen. Bei V.a. purulenten Perikarderguss muss unter Antibiotikaschutz gleichfalls eine umgehende Drainage, am besten mit nachfolgender Spülung, erfolgen. Hingegen ist die Perikardpunktion bei Aortendissektion trotz Perikardtamponade kontraindiziert. Hier ist ein unmittelbares kardiochirurgisches Vorgehen erforderlich. Obgleich eine Perikardiektomie die einzige Behandlung für eine Pericarditis constrictiva darstellt, ist sie bei erheblicher Myokardfibrose und/oder Atrophie im Computer- oder Magnetresonanztomogramm kontraindiziert.Fallbericht:Eine iatrogene Tamponade kann gelegentlich bei perkutaner Mitralklappenvalvuloplastie, der Implantation von Herzschrittmachern, elektrophysiologischen Untersuchungen mit Ablationsbehandlung, rechtsventrikulärer Endomyokardbiopsie, orthoperkutaner transluminaler Koronarangioplastie und selten bei einer Rechtsherzkatheteruntersuchung mit einem Swan-Ganz-Katheter vorkommen. Als Fallbeispiel wird über eine Perikardtamponade bei einem 79-jährigen Patienten berichtet, die infolge einer Koronarperforation bei elektiver Stentimplantation auftrat. Die Tamponade konnte mit einer Perikardpunktion, die Leckagestelle durch die Implantation eines abdeckenden Stentgrafts erfolgreich behandelt werden. Das nachfolgende „postcardiac injury syndrome“ wurde initial mit Aspirin allein, später mit der Kombination von Aspirin und Colchicin erfolgreich behandelt. Colchicin konnte nach 6 Monaten abgesetzt werden.Schlussfolgerung:Der natürliche Verlauf von Perikarderkrankungen kann durch eine Exazerbation kompliziert werden, die ihn zum perikardialen Notfall macht. Dieser erfordert eine umgehende Diagnosestellung, hämodynamisches Monitoring auf der Intensivstation sowie umgehende und rechtzeitige Einleitung der Therapie, meist einschließlich einer Perikardpunktion oder einer chirurgischen Perikardiotomie. Gleiches gilt für kardiale prozedurale Notfälle.

Magnetic resonance imaging in pericardial diseases : Indications and diagnostic value

Introduction Echocardiography is the standard for the assessment of patients with pericardial diseases. It provides valuable morphological and functional information. However, it is sometimes limited by acoustic window, low signal-to-noise ratio, and can be difficult in obese patients or in those with obstructive lung diseases [1]. Additionally, it is often of limited value in patients with loculated/localized effusions, and with the exception of transesophageal echocardiography, it is generally unreliable for the assessment of pericardial thickening [2]. Cardiac magnetic resonance imaging (MRI) is a reliable method for the assessment of the pericardium, because it offers good temporal and spatial resolution, functional and three-dimensional imaging with highly reproducible measurements without exposing patients to radiation [3].

Flexible Percutaneous Pericardioscopy: Inherent Drawbacks and Recent Advances

Pericardioscopy enables endoscopic inspection and aimed biopsy of the parietal and visceral pericardium. To elucidate possible technical modifications contributing to the feasibility, diagnostic value and safety of the procedure, pericardioscopy with and Olympus HYF-1T flexible endoscope was performed in 32 patients (53.1% males, mean age 46.2 ± 13.1 years) with pericardial effusions.In all patients, the intial step of the procedure was subxiphoid fluoroscopically controlled pericardiocentesis and drainage of the pericardial effusion. An Olympus FB-41ST biopsy forceps was applied for endoscopically guided pericardial biopsies. Standard sampling was used in 22/32 patients (3 to 6 samples/patient) and extensive sampling in 10/32 patients (18 to 20 samples/patient). In additional 12 patients pericardial biopsy was performed without pericardioscopy, under fluoroscopic control.Endoscopic visualization was clearly superior when pericardial effusion was partially replaced with 100 to 300 ml of air (29/32 procedures) in comparison to 3/32 procedures in which the pericardial effusion was replaced with warm normal saline (37 °C). In patients with hemorrhagic effusion (12/32), we either repeatedly injected and removed 100 to 150 ml volumes of normal saline (37 °C), or postponed pericardioscopy for 2 to 3 days of active drainage. The specificity of endoscopic findings is low and not decisive for the diagnosis. However, pericardioscopy is significantly contributing to the diagnostic value of pericardial biopsy, especially regarding establishing the new diagnosis and etiology of the pericardial disease. Sampling efficiency was also significantly higher for procedures using aimed pericardial biopsy with standard and extensive sampling compared to procedures performed under fluoroscopy: 86.2%, 87.3% and 43.7%, respectively. No major complications directly related to the procedure were encountered. Minor complications included: short-run ventricular tachycardia (6.3%), pain at the sheath entry site (75%) and transient fever (37.5%).In conclusion, pericardioscopy with Olympus HYF-1T, after air instillation, is a technically complex, but safe procedure that enables excellent visualization and extensive pericardial sampling with improved diagnostic value of pericardial biopsies.ZusammenfassungZiel dieser Untersuchung war es zu prüfen, welchen Stellenwert die perkutane Perikardioskopie für Diagnostik und Therapie von Patienten mit ätiologisch unklaren Perikardergüssen einnimmt und welche Verbesserungsmöglichkeiten es für die Bildgebung gibt.Bei 32 Patienten mit Perikarderguss (53,1% Männer, mittleres Alter 46,2 ± 13,1 Jahre) erfolgte die Perikardioskopie mit dem flexiblen Olympus-HYF-1T-Endoskop. Für die endoskopisch gesteuerte Perikardbiopsie wurde bei allen Patienten eine FB-41ST-Olympus-Biopsiezange verwendet. Bei 22/32 Patienten wurden drei bis sechs Proben/Patient entnommen (Gruppe 1, Standard Sampling) und bei 10/32 Patienten 18 bis 20 Proben/Patient (Gruppe 2, Extensive Sampling). Außerdem wurde die Bildqualität bei Instillation von 0,9%iger Kochsalzlösung mit der nach Instillation von Luft verglichen. Bei Patienten mit hämorrhagischem Perikarderguss (12/32) erfolgte eine Perikardspülung mit Kochsalzlösung. Die Perikardioskopie wurde zwei bis drei Tage nach Spülung und Drainage vorgenommen.Die optische Qualität der Perikardioskopie war deutlich besser nach Ersatz des Perikardergusses mit 100 bis 300 ml Luft (29/32 Prozeduren) im Vergleich zu den Patienten, bei denen der Erguss mit 0,9%iger Kochsalzlösung (37 °C) ersetzt worden war. Die Spezifität des endoskopischen Befundes allein ist gering. Dagegen trägt die Perikardioskopie insofern erheblich zur diagnostischen Wertigkeit der Epi-/Perikardbiopsie bei, als sie eine gezielte Biopsie makroskopisch auffälliger Stellen erlaubt. Die Ausbeute an Biopsien war mittels perikardioskopischer Steuerung des Bioptoms deutlich besser als unter reiner Röntgenkontrolle (86,2% in Gruppe 1, 87,3% in Gruppe 2 bei Biopsieentnahmen unter Perikardioskopie und 43,7% in Gruppe 3 unter alleiniger Röntgenkontrolle). Ventrikuläre Rhythmusstörungen (6,3%), intermittierendes Druckgefühl (75%) und kurzzeitige Temperaturerhöhungen (37,5%) waren die einzigen Komplikationen.Die Perikardioskopie mit dem Olympus HYF-1T, verbessert durch Luftinstillation, ist eine sichere Methode zur Visualisierung von Perikard und Epikard und zur Vorbereitung einer oder mehrerer Biopsien. Diese sind zusammen mit der Zytologie die Voraussetzung für eine exakte ätiologische Diagnose eines Perikardergusses.

Mineralocorticoid receptor antagonists, a class beyond spironolactone — Focus on the special pharmacologic properties of eplerenone

The renin-angiotensin-aldosterone system can be blocked at specific levels by using different classes of pharmacologic agents, including angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers and mineralocorticoid receptor antagonists. Broad use of the latter, such as spironolactone, has been limited by significant incidence of gynecomastia and other sex-related adverse effects. These problems can be overcome with use of eplerenone, a selective mineralocorticoid receptor antagonist. Eplerenone has been specifically developed to bind selectively to the mineralocorticoid receptors in order to minimize binding to the progesterone and androgen receptors. In the last decade, multiple scientific evidences have been accumulated showing the efficacy and safety of the drug in multiple clinical conditions, including heart failure and arterial hypertension. Eplerenone is generally well tolerated, with the most frequent adverse event being hyperkalemia, with sexual adverse events (i.e. gynecomastia) being more uncommon, due to the selectivity of eplerenone. This review focuses on the pharmacodynamic and pharmacokinetic properties of eplerenone, thus providing the scientific basis to fully understand drug-to-drug interactions, in particular, and its efficacy and tolerability, in general. Noteworthy, the activity of eplerenone in special conditions and different patient populations is summarized.

Anthropometric and lipid parameters trends in school children: One decade of YUSAD study

INTRODUCTION Athersclerosis is a multifactorial disease that begins in childhood. There are few reports regarding influence of risk factors on the atherosclerotic processes in early period of life and adolescence. OBJECTIVE The aim of this study was to present and analyze risk factor trends in school children over a 10-year period that were included and followed-up by the Yugoslav Study of Atherosclerosis Precursors in School Children (YUSAD Study). METHODS There were three examinations of selected population from 13 centres. The first examination was performed when children were 10 years of age (first group; N = 6381 participants), the second examination on the same population when they were 15 years of age (second group; N = 5017) and third when children were 19/20 years of age (third group; N = 1293). Evaluated parameters included: BMI, waist circumference (WaC) and lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride). RESULTS A significant elevation of values (p < 0.001) of BMI, WaC and triglycerides and a significant decline (p < 0.001) of total cholesterol and LDL cholesterol in boys over 5 and 10-year period was noticed. There was a significant elevation (p < 0.001) of BMI, WaC and HDL values and a significant decline in LDL cholesterol values in girls over the 5 and 10-year period. CONCLUSION Our results point out that girls between 10 and 19/20 years have a better lipid profile during growth. It should be stressed out that childhood and adolescence can be more beneficial in the observation of risk factor influences on pathological, genetic and clinical levels.

Physical activity evaluation in Yugoslav Study of the Precursors of Atherosclerosis in School Children - YUSAD study

Introduction It is observed that there is a lack of physical activity and exercise in children, stressing higher prevalence of childhood obesity. The purpose of the study was to evaluate duration of physical activity in a child population and correlation of dynamics in physical activity during 5 years of follow-up in the same population. Material and methods We evaluated 3243 school children from 12 regional centres across Serbia. The first examination was done when the children were 10 years old (baseline group), while the second examination was done on the same population when children were 15 years old. Physical activity was classified as recreational activity after school. We analysed 3 groups regarding physical activity: a group of children who were physically active less than 1 hour per day (group I), a second group active from 1 hour to < 3 hours per day (group II), and a third group active ≥ 3 hours per day (group III). Results In our study we have found on examination that the majority of children were physically active between 1 and 3 hours per day. Our results indicate that there is significant movement from groups I and III toward group II on the second examination regarding the proportion in the baseline group. There is a significant increase in the number of children in group I as they get older. Conclusions School children in Serbia are physically active predominantly between 1 and 3 hours per day at the age between 10 and 15 years.

The role of glycemia in acute heart failure patients

Abstract Acute heart failure (AHF) is one of the most important cardiovascular syndromes associated with high cardiovascular morbidity, and is the major cause of admission in emergency departments worldwide. The clinical complexity of AHF has significantly increased, mostly due to the comorbidities: diabetes, arterial hypertension, dyslipidemia, obesity, peripheral vascular disease, renal insufficiency and anemia. Numerous clinical trials have demonstrated a frequent association of AHF and diabetes. Since AHF is a very heterogeneous condition, it is important to identify clinical and laboratory parameters useful for risk stratification of these populations. Hyperglycemia may be one of the most convenient, since it is widely measured, easily interpreted, and inexpensive. Acute coronary syndrome (ACS), arrhythmias and poor compliance to chronic medications are considered to be the most frequent precipitating factors of AHF in diabetics. Several studies identified diabetes as the most prominent independent predictor of morbidity and mortality in both acute and chronic heart failure (HF) patients. The following parameters were identified as the independent predictors of in-hospital mortality in patients with AHF and diabetes: older age, systolic blood pressure <100 mmHg, ACS, non-compliance, history of hypertension, left ventricular ejection fraction (LVEF) <50%, serum creatinine >1.5 mg/dL, marked elevation of natriuretic peptides, hyponatremia, treatment at admission without ACE inhibitors/ARBs/β-blockers, and no percutaneous coronary intervention (PCI) as a treatment modality. The most frequent cause of AHF is ACS, both with ST segment elevation (STEMI) or without (NSTEMI). Hyperglycemia is very common in these patients and although frequently unrecognized and untreated, has a large in-hospital and mortality significance.

School children systolic and diastolic blood pressure values: YUSAD study

The aim of the study was to analyze changes of systolic and diastolic blood pressure values over five and ten years separately boys and girls and to estimate correlation between them. Three age groups from 8 centers in Serbia were evaluated: Group 1: 10 year old patients, Group 2: 15 year old and Group 3: 20 year old. Group with normal blood pressure values, prehypertensive and hypertensive group were analyzed. Regarding the period of follow-up we analyzed: 10/15 years period-children between 10 and 15 years, 15/20 years period-children between 15 and 20 years, and 10/20 years period-children between 10 and 20 years. Significant increase of diastolic blood pressure was noticed for both genders in 10/15 years period of prehypertensive population, while in hypertensive children, boys showed decline in frequency for systolic and diastolic blood pressure and girls only for diastolic. In 15/20 years period there was significant decrease of prehypertensive and significant increase of hypertensive diastolic blood pressure frequency. In 10/20 years period significant reduction in frequency of prehypertensive systolic blood pressure was noticed, while only hypertensive group of boys showed significant reduction regarding systolic blood pressure frequency. Prehypertensive diastolic and hypertensive systolic blood pressure fluctuations are more related to age.

The Natural History of Viral Myocarditis: Pathogenetic Role of Adrenergic System Dysfunction in the Development of Idiopathic Dilated Cardiomyopathy

The pathogenetic mechanisms of progression from viral myocarditis to dilated cardiomyopathy remain uncertain and controversial. With recent developments in molecular analyses of tissue specimens, new techniques of viral gene amplification and biochemical analyses, a causal link has become increasingly apparent.1-3 Perhaps the main breakthrough in the understanding of this complex clinical issue has been the demonstration of persistence of viral RNAIDNA in the myocardium beyond 90 days after inoculation, confirmed by polymerase chain reaction. Although viral myocarditis has various clinical presentations, only severe cases cause substantial cardiac injury and the development of dilated cardiomyopathy. In addition to the inflammatory injury to the myocytes, various other mechanisms are likely to be involved.4 Several studies have revealed both T-cell-immune-mediated and viral-induced cardiac injury as the predominant pathophysiologic mechanisms.4-5 However, apoptotic cell death may be another explanation behind the adverse clinical evolution of acute myocarditis.6 In addition, there is experimental and clinical evidence of the detrimental effects of a heightened sympathetic activity in acute myocarditis. Several investigators have examined the effects of exercise during Coxsackie virus B3-induced myocarditis in mice.7-9 Swimming or running on a treadmill were used as exercise stressors, increasing the heart rate and blood pressure, effects mostly mediated by catecholarnines. More extensive cardiac lesions were regularly observed in exercised than in nonexercised Coxsackie virus B3-infected mice.10 In a short-term hemodynamic study in humans, Popovic et al. showed beneficial effects of metoprolol with or without nitroglycerin, in 11 patients with biopsy-proven lymphocytic myocarditis and left ventricular dysfunction.11