INADEQUACY OF VITAMIN K ANTAGONIST USE IN PATIENTS WITH ATRIAL FIBRILLATION - OVERVIEW OF EVERYDAY CLINICAL PRACTICE AT THE MERKUR UNIVERSITY HOSPITAL IN ZAGREB, CROATIA.

Atrial fibrillation is the most common cardiac arrhythmia. It increases the risk of death and thromboembolic events. Vitamin K antagonists reduce these risks. Disadvantages of vitamin K antagonist therapy are narrow therapeutic range and interactions with drugs and food. In a single center prospective study, we enrolled 249 patients with atrial fibrillation over a 12-month period. The aim of our study was to evaluate vitamin K antagonist use regarding the indication and adequate dose. Data on 249 consecutive patients with atrial fibrillation were collected before general availability of novel oral anticoagulants. Out of 249 patients, 160 (64.2%) had indication for oral anticoagulant therapy. Only 81 (50.6%) patients had vitamin K antagonist in therapy, 12 (14.8%) of them in adequate dose. We also analyzed 129 patients aged over 75, of which 109 (84.4%) had absolute indication for oral anticoagulant therapy. Only 34 (31.2%) patients aged over 75 had been receiving vitamin K antagonist therapy and 6 (17.6%) had the International Normalized Ratio values within the proposed therapeutic interval. We found a significantly higher rate of anticoagulant therapy introduction in patients under 75 years (p=0.03), but there were no significant differences in the adequacy of anticoagulant therapy (p=0.89) between these two populations. Our results showed clear inadequacies of vitamin K antagonist treatment with a growing need for a wider use of novel oral anticoagulants.

Mortality and causes of death among Croatian male Olympic medalists.

AIM: To compare the overall and disease-specific mortality of Croatian male athletes who won one or more Olympic medals representing Yugoslavia from 1948 to 1988 or Croatia from 1992 to 2016, and the general Croatian male population standardized by age and time period. METHODS: All 233 Croatian male Olympic medalists were included in the study. Information on life duration and cause of death for the Olympic medalists who died before January 1, 2017, was acquired from their families and acquaintances. We asked the families and acquaintances to present medical documentation for the deceased. Data about the overall and disease-specific mortality of the Croatian male population standardized by age and time period were obtained from the Croatian Bureau of Statistics (CBS). Overall and disease-specific standard mortality ratios (SMR) with 95% confidence intervals (CI) were calculated to compare the mortality rates of athletes and general population. RESULTS: Among 233 Olympic medalists, 57 died before the study endpoint. The main causes of death were cardiovascular diseases (33.3%), neoplasms (26.3%), and external causes (17.6%). The overall mortality of the Olympic medalists was significantly lower than that of general population (SMR 0.73, 95% CI 0.56-0.94, P=0.013). Regarding specific causes of death, athletes' mortality from cardiovascular diseases was significantly reduced (SMR 0.61, 95% CI 0.38-0.93, P=0.021). CONCLUSIONS: Croatian male Olympic medalists benefit from lower overall and cardiovascular mortality rates in comparison to the general Croatian male population.

Association of chronic kidney disease with periprocedural myocardial injury after elective stent implantation: A single center prospective cohort study.

Coronary artery disease (CAD) is the leading cause of mortality in patients with chronic kidney disease (CKD). Patients with CKD who undergo percutaneous coronary intervention (PCI) may have more ischemic events than patients without CKD. The aim of our study was to determine the incidence of periprocedural myocardial injury (PMI) after elective stent implantation in patients with CKD using the Third Joint ESC/ACCF/AHA/WHF PMI definition.In a single center prospective cohort study, we enrolled 344 consecutive patients who underwent elective PCI in a period of 39 months. Serum troponin I (cTnI) concentrations were measured at baseline and at 8 and 16 hours after PCI. Periprocedural increase of cTnI, according to the most recent PMI definition, was used to define both the presence and intensity of PMI. Patients were further stratified according to the estimated glomerular filtration rate (eGFR) using 4 variable Modification of Diet in Renal Disease (MDRD) equation: control group with eGFR >90 mL/min/1.73 m and the CKD group with eGFR < 90 mL/min/1.73 m, with further subdivision according to the CKD stage.We found no significant difference in the incidence as well as intensity of the PMI in the control (>90 mL/min/1.73 m) and the CKD group (<90 mL/min/1.73 m) both 8 and 16 hours after PCI. When the CKD patients were further subdivided according to their CKD stage, there was again no difference in the intensity or incidence of PMI compared to the control group. Further analyses of our data showed angina pectoris CCS IV, bare metal stent (BMS) implantation, and treatment with angiotensin-converting enzyme inhibitors (ACEI) as independent predictors of PMI. Furthermore, the presence of hypertension was inversely related to the occurrence of PMI.Applying the new guidelines for PMI and using the eGFR equation most suitable for our patients, we found no association between PMI and CKD. Further analyses showed other factors that could potentially influence the occurrence of PMI.

[Resistant hypertension and reasons for excluding patients from treatment with renal denervation]. / Rezistentna hipertenzija i razlozi iskljucivanja za postupak renalne denervacije.

Increased activation of the sympathetic nervous system is identified as an important factor in the development and progression of hypertension. In this context, a catheter-based approach has been developed to disrupt the renal sympathetic nerves, i.e. renal denervation. Among patients with resistant hypertension, it is very important to select patients using standardized stepwise screening. The potential success of renal denervation depends on the ability to select patients most likely to benefit. A multidisciplinary meeting in necessary. In this work, we describe the potential reasons for excluding patients from treatment with renal denervation.

[The effects of trimetazidine on QT-interval prolongation in patients with chronic kidney disease stage III-IV (predialysis CRD)]. / Ucinak trimetazidina na produljeni QT interval u bolesnika s kronicnom bubreznom bolesti III.-IV. stupnja (predijalizna kronicna bubrezna bolest).

Prolonged QT interval is a predictor of cardiovascular mortality. It indicates delayed repolarization of ventricular myocardium and is considered a precursor of malignant cardiac arrhythmias and sudden cardiac death. Increased cardiovascular risk (CVR) in the presence of prolonged QT interval, corrected by heart rate (QTc), is attributed to ventricular electrical instability. Patients with chronic renal disease (CRD) usually die from sudden cardiac death before reaching the final stage, final chronic kidney disease (CRD stage V). We investigated whether patients with CRD stage III-V have prolonged QT interval, what are the possible causes of this extension, and whether in this patient population trimetazidine application may affect the reduction in QT prolongation. Our study showed one quarter of predialysis patients, mostly asymptomatic, to have QT prolongation, thus being at a higher risk of CV events. Introducing trimetazidine along with standard therapy can reduce the incidence of sudden cardiac death, and calculation of the QTc index would be a useful and economical method of screening and monitoring high risk patients.

[Ten years after publishing results from The Heart Outcomes Prevention Evaluation Study--HOPE: implications on treatment with angiotensin converting enzyme inhibitors in clinical practice]. / Deset godina od objave ispitivanja The Heart Outcomes Prevention Evaluation Study--HOPE: znacenje rezultata na primjenu inhibitora angiotenzin-konvertirajuceg enzima u klinickoj praksi.

Ten years ago results from The Heart Outcomes Prevention Evaluation Study were published. Those results had a great impact on position of ACE inhibitors in clinical practice. In the study, comparison of ramipril in daily dosage up to 10 mg and placebo in 9541 patients with high cardiovascular risk during 4.5 years of follow-up resulted in relative risk reduction for all primary end-points: cardiovascular mortality, myocardial infarction and stroke for 22% in patients treated with ramipril. Systolic blood pressure was reduced minimally for 3 mmHg. The effect was independent of age, gender, concomitant diseases or therapy. Extended follow-up of the patients for further 2.6 years showed prolonged beneficial effect of ramipril. Ramipril reduced relative risk for newly developed diabetes for 34%. Results of the study greatly influenced the guidelines for treatment of patients with cardiovascular diseases. This study proved benefits of ACE inhibitors in primary prevention in patients with high cardiovascular risk.

[Antiaggregation therapy after percutaneous coronary intervention in a patient with thrombocytopenia: case report]. / Antiagregacijska terapija nakon perkutane koronarne intervencije kod bolesnika s trombocitopenijom--prikaz bolesnika.

Dual antiaggregation (antiplatelet) therapy is mandatory in patients having received a stent during percutaneous coronary intervention. This therapy usually consists of acetylsalicylic acid (100 mg per day) and clopidogrel (75 mg per day) for at least 6 to 12 months (depending on the type of stent). Such therapy has been shown to reduce significantly unwanted clinical events, although slightly increasing the risk of bleeding. Coronary stents must rarely be implanted in patients who have or develop thrombocytopenia. In such patients, the risk of bleeding is increased manifold. On the other hand, the risk of potentially fatal thrombotic events is unknown. In this case report, we present a patient who developed thrombocytopenia shortly (one month) after the stent had been implanted. After thorough clinical workup, we could not find the remediable cause of thrombocytopenia. Because of the potential of acetylsalicylic acid to induce thrombocytopenia, it was excluded from therapy and a double dose of clopidogrel (150 mg per day) was introduced. Then we decided to evaluate platelet function with the ADP aggregation test (which indicates the degree to which the function of platelets is blocked by clopidogrel) and aspirin resistance test (which indicates the degree to which the function of platelets is blocked by acetylsalicylic acid). In the first set of tests, the patient was shown to be hyperreactive to both substances. We then lowered the dose of clopidogrel to the standard dose and evaluated the function of platelets with the same tests two weeks later and the results were the same. Because the patient was without obvious and laboratory signs of bleeding, we decided not to change the prescribed antiplatelet therapy because of fear from potentially fatal thrombotic events. The use of dual antiplatelet therapy in patients with thrombocytopenia is particularly challenging. We believe that in such patients, firstly, the cause of thrombocytopenia should be sought for by thorough clinical investigation. If not found, as in our patient, tailoring of such therapy should be done using currently available aggregation tests. In such a way, patients could be protected from both excessive bleeding and potentially devastating thrombotic events. Unfortunately, this is a sole example and definite conclusions could only be made on larger studies.

[Pleural mesothelioma--case report]. / Mezoteliom pleure--prikaz bolesnika.

Pleural mesothelioma is a rare neoplasm with the incidence of 1-2 per million people. The incidence is higher in male population (10-30/million), whereas the incidence in female population is 2 per million. It occurs predominantly at older age (65+ years). The most common clinical manifestation of pleural mesothelioma is pleural effusion with dyspnea, which makes it a diagnostic problem since many cardiac diseases can have the same presentation. We report a case of pleural mesothelioma in an 80-year-old woman that presented with dyspnea and pleural effusion, which was at first considered as a sign of heart failure. Clinical presentation also included metabolic disorders and deep vein thrombosis, and the patient's epidemiologic history was negative, so diagnostic procedures including pleurocentesis were directed towards detection of the possible malignant disease. Cytologic analysis followed by biopsy pointed to the diagnosis of pleural mesothelioma. Persistent pleural effusions that do not coincide with cardiac disease, especially if accompanied by metabolic disorders and paraneoplastic syndromes, require additional diagnostic workup to identify the etiology of pleural effusion.

[Secondary (AA) renal/bone amyloidosis complicating rheumatoid arthritis]. / Sekundarna amiloidoza (AA) bubrega i kostane srzi u bolesnice s reumatoidnim artritisom.

Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that appears in the context of cancer, chronic inflammation, and chronic infectious disease, including rheumatoid arthritis. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. We present a case of a 52-year-old female patient diagnosed with rheumatoid arthritis at age 27. She was hospitalized due to worsening clinical condition. Physical examination revealed marked peripheral edema in both lower extremities. Laboratory tests showed an increase of inflammatory reactants, anemia, electrolyte disbalance, and severe hypoalbuminemia and hypoproteinemia. She had proteinuria 15.4 g/24 h and renal function estimated by creatinine clearance was 78 mL/min, within the second degree of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposits that immunoreacted with the antibody against amyloid A protein, thus confirming the diagnosis of secondary amyloidosis.

[Guidelines for diagnostics and treatment of arterial hypertension. Practical recommendations of the Croatian Working Group for Hypertension. Consideration on the ESH-ESC 2007 guidelines]. / Smjernice za dijagnosticiranje i lijecenje arterijske hipertenzije. Prakticne preporuke hrvatske radne skupine i osvrt na smjernice ESH/ESC 2007.

ESH/ECS guidelines for diagnostics and treatment of arterial hypertension 2007 is a basic paper for all physicians who treat hypertensive patients. Since publishing, this article has been the most cited medical paper. According to ESH/ECS guidelines some local peculiarities in each country should be considered when diagnosing and treating hypertensive patients. Practical recommendations of the Croatian working group for the diagnostics and treatment of hypertension are in agreement with ESH/ECS guidelines. However, few additional issues are added and further discussed in this paper (hypertensive crisis, treatment of hypertension in patients undergoing dialysis and in renal transplanted patients, role of family physicians, role of nurse). We believe that this paper will contribute better control of hypertension in Croatia. All medical societies and institutions that took part in writing this document, have to consider this paper as an official statement.

[The role of endothelium in hypertension and atherosclerosis]. / Mjesto i uloga endotela u hipertenziji i aterosklerotskim procesima.

Endothelium was "discovered" as a separate organ in the last decades of the previous century. For a long time endothelial cells were considered as a very passive monolayer of cells just covering the inner part of vascular walls. The role of these cells was thought to be only a mechanical barrier between circulating blood and vascular structures. Nowadays, after a series of biochemical and experimental studies, one can name endothelium as an organ, covering approximately 700 sqaure meters, weighing about 1.5 kilos in an average male with weight of 70 kg. Not only its quantity, but also its function is amazing. The most prominent and first well studied function of endothelial cells is vasodilatation and vasoconstriction. Normal cells, which are intact and in function produce regularly one of the most important protecting agent in circulation: NO. Normal endothelial cells produce NO as a result of higher blood pressure or growing demand for oxygen. It is produced from aminoacid L-arginine as a result of enzyme activity: endothelial NO synthetase (eNOS). Interleukins also can increase production of NO. NO has also antiinflammatory efects, helping in reparation and healing processes. Prostacyclins are the second most important vasodilating agent produced in endothelium. On the other hand, vasoconstriction is also mediated via endothelium. Endothelin 1, angiotensin II and thromboxan A are produced in vascular wall by endothelial cells, acting as opponent to NO. ACE system is very active inside those cells, with permanent local angiotensin II formation, that mostly act on vascular wall itself. Effects of such generated angiotensin II stimulate activation of VCAM molecules, starting adhesion of monocytes, their penetration in vascular wall and activation. Acivated macrophages get in contact with oxidized LDL particles already inside the vascular wall, producing foam cells. That is the very begining of atherosclerosis. All negative effects of excess of angiotensin II should be reduced by effective therapy with ACE inhibitors or AT antagonists. Today it seems more important to act on excess in endothelial AII in order to regulate not only blood pressure, but long-term devastating effects on target organs, preventing atherosclerosis.