Patterns of anticoagulation therapy in atrial fibrillation: results from a large real-life single-center registry.

AIM: To investigate the differences in the characteristics and clinical outcomes of recently diagnosed patients with atrial fibrillation (AF) receiving different types of anticoagulants in a real-life setting. METHODS: We retrospectively analyzed the charts of 1000 consecutive patients with non-valvular AF diagnosed at our institution or referred it to from 2013 to 2018. RESULTS: Over the observed period, the frequency of direct oral anticoagulation (DOAC) therapy use significantly increased (P = 0.002). Patients receiving warfarin had more unfavorable thromboembolic and bleeding risk factors than patients receiving DOAC. Predetermined stroke and major bleeding risks were similarly distributed among the dabigatran, rivaroxaban, and apixaban groups. Patients receiving warfarin had shorter time-to-major bleeding (TTB), time to thrombosis (TTT), and overall survival (OS) than patients receiving DOACs. After adjustment for factors unbalanced at baseline, the warfarin group showed significantly shorter OS (hazard ratio 2.27, 95% confidence interval 1.44-3.57, P<0.001], while TTB and TTT did not significantly differ between the groups. Only 37% of patients on warfarin had optimal dosing control, and they did not differ significantly in TTB, TTT, and OS from patients on DOACs. CONCLUSION: Warfarin and DOACs are administered to different target populations, possibly due to socio-economic reasons. Patients receiving warfarin rarely obtain optimal dosing control, and experience significantly shorter survival compared with patients receiving DOACs.

Mitochondrial unfolded protein response, mitophagy and other mitochondrial quality control mechanisms in heart disease and aged heart.

Mitochondria are involved in crucial homeostatic processes in the cell: the production of adenosine triphosphate and reactive oxygen species, and the release of pro-apoptotic molecules. Thus, cell survival depends on the maintenance of proper mitochondrial function by mitochondrial quality control. The most important mitochondrial quality control mechanisms are mitochondrial unfolded protein response, mitophagy, biogenesis, and fusion-fission dynamics. This review deals with mitochondrial quality control in heart diseases, especially myocardial infarction and heart failure. Some previous studies have demonstrated that the activation of mitochondrial quality control mechanisms may be beneficial for the heart, while others have shown that it may lead to heart damage. Our aim was to describe the mechanisms by which mitochondrial quality control contributes to heart protection or damage and to provide evidence that may resolve the seemingly contradictory results from the previous studies.

Patients with atrial fibrillation and mid-range ejection fraction differ in anticoagulation pattern, thrombotic and mortality risk independently of CHA2DS2-VASC score.

Atrial fibrillation (AF) patients with mid-range left ventricular ejection fraction (mrEF) of 40-49% have neither preserved (pEF > 50%) nor reduced (rEF < 40%) EF and are increasingly being recognized as a distinct group with specific clinical risks. We aimed to retrospectively investigate clinical characteristics and associated thrombotic, bleeding and mortality risks of mrEF in comparison to pEF and rEF in a cohort of 1000 non-valvular AF patients presenting in our institution during the period 2013-2018. Patients with mrEF presented with older age (P < 0.001) and a higher frequency of arterial hypertension (P = 0.001) in comparison to both pEF and rEF patients. In comparison to pEF, mrEF patients were more likely to have diabetes mellitus (P = 0.004), lower HDL-cholesterol (P < 0.001) and lower estimated glomerular filtration rate (P < 0.001), significantly higher CHA2DS2-VASC score (P < 0.001), significantly higher HAS-BLED score (P = 0.002) and had a higher likelihood of receiving anticoagulant therapy, mostly warfarin (P = 0.001). In addition, mrEF patients had a significantly higher risk of thrombotic events (HR = 2.22; P = 0.015), death (HR = 1.71; P = 0.005) and composite endpoint of thrombosis, bleeding or death (HR = 1.65; P = 0.003) in comparison to pEF patients, but did not significantly differ in comparison to rEF patients. There was no significant difference regarding major bleeding risk. Associations with clinical outcomes remained statistically significant in multivariate models independently of CHA2DS2-VASC. Our findings support defining AF patients with mrEF as a subgroup with distinct clinical characteristics and increased risk for thrombotic events and death, irrespective of predetermined CHA2DS2-VASC risk. These patients seem to require special clinical considerations and more intensive control of cardiovascular risk factors.

Patients with higher body mass index treated with direct / novel oral anticoagulants (DOAC / NOAC) for atrial fibrillation experience worse clinical outcomes.

INTRODUCTION: Due to fixed dosing of direct oral anticoagulants (DOACs), uncertainty exists about their efficacy in a population of obese/overweight patients. PATIENTS AND METHODS: We retrospectively investigated a real-life cohort of 325 DOAC anticoagulated patients with atrial fibrillation [179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%)]. Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI <30 kg/m2), class I obesity (71 with BMI 30-34.9 kg/m2) and class II + obesity (21 with BMI ≥35 kg/m2). RESULTS: Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA2DS2VASC and HAS-BLED. CONCLUSION: Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.

Primary Left Atrial Angiosarcoma Presenting as Acute Coronary Syndrome.

Primary cardiac neoplasms are extremely rare and often overlooked as differential diagnosis. Angiosarcomas are the most common primary malignant neoplasms of the heart often with nonspecific symptoms. We present a 43-year-old woman admitted to our hospital with chest pain and inferoposterolateral myocardial infarction. Coronary angiography indicated the distal occlusion of the left circumflex artery. Transthoracic and transoesophagic echocardiography revealed a mass in the left atrium with probable myocardial infiltration and vascularisation. The mass in the left atrium was removed by surgical resection, and histopathology confirmed angiosarcoma. We emphasize the pivotal role of transthoracic and transoesophageal echocardiography in evaluating even rare differential diagnosis of acute coronary syndrome as cardiac neoplasms.

Suggesting a New Primary Access Site for Treating Chronic Total Occlusions: Bilateral Distal Transradial Intervention (bdTRI).

Bilateral distal transradial intervention is a new primary access strategy for chronic total occlusion interventions. We provide a brief review of recent studies and offer the rationale behind this promising approach.

Prognostic value of lactates in relation to gas analysis and acid-base status in patients with pulmonary embolism.

AIM: To assess the prognostic value of lactate level for mortality in patients with pulmonary embolism (PE) and Pulmonary Embolism Severity Index (PESI) I-III and its independence of gas-analysis parameters and acid-base status. METHODS: This prospective observational study was conducted at the University Clinical Hospital Mostar from 2013 to 2017. On the first day after PE diagnosis, 1.5 mL of arterial blood was collected from 103 patients with PE. Partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, blood pH value, concentration of bicarbonates in arterial blood (HCO3-), base deficit, and oxygen saturation were analyzed. Lactate levels were assessed using blood samples taken from the cubital vein. Logistic regression analysis was used to assess the predictive value of gas-analysis variables, lactate level, PESI score, age, and sex for in-hospital death due to PE. RESULTS: The mortality in the group of PE patients was 19.1% (18 of 103 patients). Lactate level was an independent predictor of mortality (P=0.002, odds ratio 0.06). HCO3- was also found to be a significant predictor (P=0.022, odds ratio 2.4). Lactates were independent of other variables. Other gas-analysis parameters were not significant predictors of mortality. CONCLUSION: In PE patients at low-intermediate risk of mortality (PESI I-III), lactate level was associated with a short-term mortality, independently of other gas-analytic parameters. Oxford Centre for Evidence-based Medicine level of evidence: 2.

The Significance of Thallium-201-Chloride SPECT Myocardial Perfusion Imaging in the Management of Patients With Stable Chronic Coronary Artery Disease.

BACKGROUND: Patients with stable coronary artery disease (CAD) can be evaluated for myocardial viability by examining reverse redistribution of Thallium-201 (201TI) through cardiac scintigraphy. There is limited knowledge about association of a reverse redistribution with favorable cardiac outcomes. In this study, we hypothesized that higher left ventricular ejection fraction (LVEF), lower myocardial necrosis, fewer ischemic events, and less angina will be associated with reverse redistribution of 201TI imaging. METHODS: Adult patients with stable CAD included in this study underwent exercise-redistribution Thallium single-photon emission computed tomography (SPECT) and were followed for one year. LVEF and regional wall motion abnormalities were evaluated with echocardiography, exercise duration by bicycle testing, and myocardial ischemia and viability by Thallium SPECT. RESULTS: We studied 159 patients (87 men, 72 women, median age 60 years, range: 38-84) with well-developed collaterals. Those with reverse redistribution on SPECT (n = 61, 38.3%) had significantly better exercise tolerance (⩾85%; P < .001). Subjects with reverse redistribution had better LVEF (P < .001), wall motion parameters (P < .001), a lower degree of myocardial necrosis (P < .05), less angina during follow-up (P = .02), and fewer ischemic events whether treated with OMT or PCI (P < .001). CONCLUSIONS: Reverse redistribution of 201Tl on scintigraphic images is a predictor of myocardial viability. Evidence from our study suggests that optimally treated chronic CAD patients with reverse redistribution may have lower likelihood of future adverse cardiovascular events and better prognosis.

Pacemaker Implantation Associated Myocardial Micro-Damage: A Randomised Comparison between Active and Passive Fixation Leads.

Fixation of the pacemaker leads during pacemaker implantation leads to an increase of cardiac Troponin T (cTnT) that can be interpreted as a sign of minimal myocardial damage. This trial evaluates whether the mechanism type of lead fixation influences the magnitude of cTnT release. Patients having a de-novo cardiac pacemaker implantation or a lead revision were centrally randomized to receive either a ventricular lead with an active (screw) or passive (tine) fixation mechanism. High-sensitive Troponin T (hsTnT) was determined on the day of the procedure beforehand and on the following day. 326 Patients (median age (IQR) 75.0 (69.0-80.0) years, 64% male) from six international centers were randomized to receive ventricular leads with an active (n = 166) or passive (n = 160) fixation mechanism. Median (IQR) hsTnT levels increased by 0.009 (0.004-0.021) ng/ml in the group receiving screw-in ventricular leads and by 0.008 (0.003-0.030) ng/ml in the group receiving tined ventricular leads (n.s.). In conclusion pacemaker implantations are followed by a release of hsTnT. The choice between active or passive fixation ventricular leads does not have a significant influence on the extent of myocardial injury and the magnitude of hsTnT release.

Subadventitial stenting around occluded stents: A bailout technique to recanalize in-stent chronic total occlusions.

OBJECTIVES: To evaluate the outcomes of subadventitial stenting (SS) around occluded stents for recanalizing in-stent chronic total occlusions (IS-CTOs). BACKGROUND: There is little evidence on the outcomes of SS for IS-CTO. METHODS: We examined the outcomes of SS for IS-CTO PCI at 14 centers between July 2011 and June 2017, and compared them to historical controls recanalized using within-stent stenting (WSS). Target-vessel failure (TVF) on follow-up was the endpoint of this study, and was defined as a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization. RESULTS: During study period, 422 IS-CTO PCIs were performed, of which 32 (7.6%) were recanalized with SS, usually when conventional approaches failed. The most frequent CTO vessel was the right coronary artery (72%). Mean J-CTO score was 3.1 ± 0.9. SS was antegrade in 53%, and retrograde in 47%. Part of the occluded stent was crushed in 37%, while the whole stent was crushed in 63%. Intravascular imaging was used in 59%. One patient (3.1%) suffered tamponade. Angiographic follow-up was performed in 10/32 patients: stents were patent in six cases, one had mild neointimal hyperplasia, and three had severe restenosis at the SS site. Clinical follow-up was available for 29/32 patients for a mean of 388 ± 303 days. The 24-month incidence of TVF was 13.8%, which was similar to historical controls treated with WSS (19.5%, P = 0.49). CONCLUSIONS: SS is rarely performed, usually as last resort, to recanalize complex IS-CTOs. It is associated with favorable acute and mid-term outcomes, but given the small sample size of our study additional research is warranted.

Association between Circulatory and Plaque Resistin Levels with Carotid Plaque Instability and Ischemic Stroke Events.

ses of ischemic stroke. The risk of ischemic stroke increases with the degree of carotid stenosis and plaque vulnerability. The aim of this study was to investigate the association of circulating and plaque resistin levels with plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis. METHODS: 40 patients with ischemic stroke events and 38 neurologically asymptomatic patients scheduled for carotid endarterectomy were recruited for this study. Fasting blood samples for laboratory analysis were collected preoperatively and serum resistin levels were measured by enzyme-linked immunosorbent assays. Carotid endarterectomy specimens were analyzed according to the gold-standard procedure of histological classification. Plaque resistin expression was determined by standard immunohistochemical procedure. RESULTS: Serum resistin levels and resistin plaque expression were found to be significantly higher in subjects with unstable carotid plaque (P < .001) while significantly higher serum resistin levels were also present in patients with ischemic stroke events (P < .001). In univariate stepwise logistic regression analysis, higher serum resistin levels were significantly associated with plaque instability (OR 2.223, 95% CI 1.488-3.320, P < .0001) and ischemic stroke events (OR 1.237, 95% CI 1.079-1.420, P = .002). There was also a significant association between higher serum and plaque resistin expression (OR 1.663, 95% CI1.332-2.077, P < .0001). These associations remained significant in all models of multivariate logistic regression analysis. High serum and plaque resistin levels were also significantly associated with specific histological features of plaque instability. CONCLUSION: The results suggests that serum resistin levels may be used as a potential biomarker of plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis and highlight the possible relationship that plaque resistin expression has with histological features of plaque vulnerability.

Successful treatment of annular rupture during transcatheter aortic valve implantation.

Annular rupture presents a rare but potentially fatal complication of transcatheter aortic valve implantation (TAVI). Although it can be subtle and subclinical in presentation, most severe forms present with hemodynamic instability and represent true emergencies requiring a more invasive treatment, even conventional surgery. We present a case of successful treatment of annular rupture by left ventricular outflow tract patch and surgical aortic valve replacement.

Arterial stiffness in patients with coronary artery disease: relation with in-stent restenosis following percutaneous coronary intervention.

BACKGROUND: Coronary artery disease (CAD) is one of the most important issues in modern medicine due to its high mortality and prevalence. An early detection and prevention can reduce morbidity and mortality. Arterial stiffness is a potent and independent predictor of CAD. We aimed to investigate the arterial stiffness in CAD patients undergoing the coronary angiography. Also, we investigated a possible correlation between arterial stiffness and in-stent restenosis (ISR), an important limitation of percutaneous coronary intervention (PCI). METHODS: The study included 160 patients undergoing coronary angiography, treated either with PCI or with CABG. The pulse wave velocity (PWV) and augmentation index (AIx) were measured by the Arteriograph. RESULTS: PWV in the CAD group (12.24 ± 2.78 m/s) was significantly higher compared to the control group (8.27 ± 1.89 m/s). PWV in ISR and left main (LM) stenosis group (14.03 ± 3.15 and 13.89 ± 2.95 m/s) was significantly higher compared to the control and CAD groups. Peripheral and central AIx were significantly higher in CAD group (1.38 ± 30.63 % and 38.35 ± 15.52 %) than in control group (-11.35 ± 26.74 % and 26.91 ± 10.62 %). Patients with LM stenosis have significantly higher values of peripheral and central AIx (23.37 ± 23.77 % and 49.71 ± 12.02 %) than the CAD and ISR group. CONCLUSIONS: The study confirmed a positive correlation between arterial stiffness measures, PWV and AIx, and CAD. Also, this study showed the correlation between PWV and ISR which can help to select more appropriate stent.

Ventricular tachycardia: ominous sign of devastating prosthetic aortic valve dehiscence.

Prosthetic valve endocarditis (PVE) is the most feared complication after valve implantation. It usually results in substantial morbidity and mortality in the postoperative period. An adverse effect on the annulus can cause conduction disturbances in the atrioventricular (AV) node, resulting in a high-degree AV block. This study describes a case of PVE that predominantly presented with sustained monomorphic ventricular tachycardia, which indicated a severe clinical course of PVE caused by a significant displacement of the aortic valve prosthesis. In our opinion, a very pronounced flap valve motion of the dehisced valve probably caused, in the critical moment, coronary artery blood flow limitation by means of coronary microembolization, which produced temporary ischemia and provoked sustained ventricular tachycardia. Furthermore, disturbances of rhythm such as ventricular tachycardia in the setting of endocarditis indicate a high-risk condition and should mandate fast and thorough noninvasive diagnostic procedures to obtain correct diagnosis even in the case of mild, slowly progressing disease.

SEVEN-YEAR TRENDS IN THE CROATIAN PRIMARY PERCUTANEOUS CORONARY INTERVENTION NETWORK.

The authors investigated trends in the Croatian primary Percutaneous Coronary Intervention (pPCI) Network results among three consecutive time intervals (2005-2007, first phase; 2008-2009, second phase; and 2010-2011, third phase). Data on 5650 patients with acute myocardial infarction with ST-elevation (STEMI) transferred or directly admitted and treated with pPCI in 11 Croatian PCI centers during the study period were collected and analyzed. The number of patients with acute STEMI treated with pPCI per year rose continuously during the study period (581 vs. 1272 vs. 1949 patients/year). The patient risk profile worsened during the study period: age (60 vs. 61 vs. 63 years; p<0.01), anterior myocardial wall involvement (43% vs. 44% vs. 51%; p<0.01), shock rate (7% vs. 9% vs. 11%; p<0.05), and percentage of transferred patients (42% vs. 36% vs. 46%; p<0.01). While the door-to-balloon time shortened (108 vs. 98 vs. 75 min; p<0.01), the symptom onset-to-door time increased (130 vs. 175 vs. 195 min; p<0.01), but without statistically significant influence on the total ischemic time. Multivariate log-linear analysis eliminated influence of a higher risk profile on the results of treatment and yielded no statistically significant changes in final TIMI 3 flow (Thrombolysis In Myocardial Infarction 3), in-hospital mortality, and six-month mortality rate, but revealed a significant increase in the rate of angina pectoris (12 vs. 22 vs. 36%; p<0.01) and other major adverse cardiovascular events (MACE; 6 vs. 23 vs. 14%; p<0.01) during follow up. In conclusion, the Croatian pPCI Network continuously ensures very good results of STEMI treatment in this economically less developed European country despite worsening of the risk profile in treated patients and opening of new, less experienced PCI centers. The higher percentage of MACE over time could be explained by changes in the pPCI strategy introduced over time (the culprit lesion only) and higher availability of PCI centers for additional PCI after acute STEMI. However, there is room for improvement, especially in reducing prehospital delay.

Polymorphisms in DNA repair genes: link with biomarkers of the CBMN cytome assay in hospital workers chronically exposed to low doses of ionising radiation.

Individual sensitivity to ionising radiation (IR) is the result of interaction between exposure, DNA damage, and its repair, which is why polymorphisms in DNA repair genes could play an important role. We examined the association between DNA damage, expressed as micronuclei (MNi), nuclear buds (NBs), and nucleoplasmic bridges (NPBs) and single nucleotide polymorphisms in selected DNA repair genes (APE1, hOGG1, XRCC1, XRCC3, XPD, PARP1, MGMT genes; representative of the different DNA repair pathways operating in mammals) in 77 hospital workers chronically exposed to low doses of IR, and 70 matched controls. A significantly higher MNi frequency was found in the exposed group (16.2±10.4 vs. 11.5±9.4; P=0.003) and the effect appeared to be independent from the principal confounding factor. Exposed individuals with hOGG1, XRCC1, PARP1, and MGMT wild-type alleles or APEX1, as well as XPD (rs13181) heterozygous showed a significantly higher MNi frequency than controls with the same genotypes. Genetic polymorphism analysis and cytogenetic dosimetry have proven to be a powerful tool complementary to physical dosimetry in regular health surveillance programmes.

Diagnostic value of MPO in patients admitted for suspected acute coronary syndrome--a study of adult in Mostar, Bosnia and Herzegovina.

We assessed the diagnostic efficacy of plasma Myeloperoxidasis (MPO) alone or in combination with cardiac troponin I (cTnI) for detecting ACS in patients presenting with chest pain initiating within 24 h before the hospital admission. In this prospective cohort study were included all respondents who have visited outpatient clinic of internal diseases, University Hospital Mostar because of chest pain and suspected acute coronary syndrome within 24 h of the onset of the period of 6 months and the total sample consisted of 114 patients. Troponin and myeloperoxidase were significantly positively correlated at the beginning of treatment, myeloperoxidase was significantly positively associated with adverse cardiovascular events during hospitalization and myocardial infarction (p < 0.05), with the regression analysis did not show a significant predictor in the development of myocardial infarction (p > 0.05). Sensitivity of myeloperoxidase as a valid test detection of myocardial infarction at baseline was 0.15 and specificity was 0.85, suggesting good diagnostic value usable in the clinical practice.

Multiple multilateral coronary-cameral fistulae in a patient with minor cardiac venous system.

A 40-year-old man was hospitalized in the coronary care unit with chest pain and abnormal electrocardiogram. Twenty days earlier, the patient underwent laparoscopic gallbladder surgery. Due to chest pain and ischemic ECG changes, patient was subjected to coronary angiography. The selective coronary angiography revealed multiple multilateral fistulae arising from the left anterior descending artery, circumflex artery, and the right coronary artery draining to the left ventricle. Multislice computed tomography showed hypoplastic coronary sinus and minor cardiac venous system.

Aortic valve endocarditis in a transplanted heart after urethral instrumentation.

Endocarditis represents a rare but life-threatening condition after heart transplantation. Recent American Heart Association guidelines recognize cardiac transplant patients with valvulopathy as high risk for endocarditis, but acknowledge that there were not sufficient data to make a recommendation for prophylaxis. Also, genitourinary procedures were no longer considered a risk factor for endocarditis in the most recent guidelines. We present a patient who acquired aortic valve endocarditis of the intact valve, after multiple urethral instrumentation 2 years after heart transplantation, who was successfully treated by aortic valve replacement and prolonged antibiotic therapy.