Common P-glycoprotein (ABCB1) polymorphisms do not seem to be associated with the risk of rivaroxaban-related bleeding events: Preliminary data.

Introduction: Considering conflicting previous reports, we aimed to evaluate whether the common ABCB1 polymorphisms (rs1128503, rs2032582, rs1045642, rs4148738) affected the risk of bleeding in rivaroxaban-treated patients. Materials and methods: We report preliminary data from a larger nested case-control study. Consecutive adults started on rivaroxaban for any indication requiring > 6 months of treatment were followed-up to one year. Patients who experienced major or non-major clinically relevant bleeding during the initial 6 months were considered cases, whereas subjects free of bleeding over > 6 months were controls. The polymorphisms of interest (rs1128503, rs2032582, rs1045642, rs4148738) were in a strong linkage disequilibrium, hence patients were classified regarding the "load" of variant alleles: 0-2, 3-5 or 6-8. The three subsets were balanced regarding a range of demographic, comorbidity, comedication and genetic characteristics. A logistic model was fitted to probability of bleeding. Results: There were 60 cases and 220 controls. Raw proportions of cases were similar across the subsets with increasing number of ABCB1 variant alleles (0-2, N = 85; 3-6, N = 133; 6-8, N = 62): 22.4%, 21.8%, and 19.4%, respectively. Fully adjusted probabilities of bleeding were also similar across the subsets: 22.9%, 27.5% and 17.7%, respectively. No trend was observed (linear, t = -0.63, df = 273, P = 0.529; quadratic, t = -1.10, df = 273, P = 0.272). Of the 15 identified haplotypes, the completely variant (c.1236T_c.2677T(A)_c.3435T_c.2482-2236A) (40.7%) and completely wild-type (C_G_C_G) (39.5%) haplotypes prevailed, and had a closely similar prevalence of cases: 21.1% vs. 23.1%, respectively. Conclusions: The evaluated common ABCB1 polymorphisms do not seem to affect the risk of early bleeding in patients started on rivaroxaban.

Safety and efficacy of dual antiplatelet therapy after percutaneous coronary interventions in patients with end-stage liver disease.

The prevalence of coronary artery disease (CAD) increases in patients with end-stage liver disease, with part of them receiving the percutaneous coronary intervention (PCI) as a treatment option. Dual antiplatelet therapy (DAPT), a standard of care after PCI, could result in catastrophic consequences in this population. Before PCI and the start of DAPT, it is recommended to assess patient bleeding risk. Based on novel findings, liver cirrhosis does not necessarily lead to a significant increase in bleeding complications. Furthermore, conventional methods, such as the international normalized ratio, might not be appropriate in assessing individual bleeding risk. The highest bleeding risk among cirrhotic patients has a subgroup with severe thrombocytopenia (< 50 × 109/L) and elevated portal pressure. Therefore, every effort should be made to maintain thrombocyte count above > 50 × 109/L and prevent variceal bleeding. There is no solid evidence for DAPT in patients with cirrhosis. However, randomized trials investigating short (one month) DAPT duration after PCI with new drug-eluting stents (DES) in a high bleeding risk patient population can be implemented in patients with cirrhosis. Based on retrospective studies (with older stents and protocols), PCI and DAPT appear to be safe but with a higher risk of bleeding complications with longer DAPT usage. Finally, novel methods in assessing CAD severity should be performed to avoid unnecessary PCI and potential risks associated with DAPT. When indicated, PCI should be performed over radial artery using contemporary DES. Complementary medical therapy, such as proton pump inhibitors and beta-blockers, should be prescribed for lower bleeding risk patients. Novel approaches, such as thromboelastography and "preventive" upper endoscopies in PCI circumstances, warn clinical confirmation.

Atrial fibrillation as a contributing factor in the diagnostic algorithm for coronary subclavian steal syndrome and cardiac tamponade following coronary artery bypass graft surgery: a case study.

Coronary subclavian steal syndrome (CSSS) is a complication of coronary artery bypass graft (CABG) surgery in patients with coexistent significant subclavian artery stenosis (SAS). It is characterized by a retrograde blood flow through the left internal mammary artery graft from the coronary to subclavian circulation, leading to myocardial ischemia. Current screening for CSSS includes bilateral blood pressure measurement for the detection of a significant inter-arm blood pressure difference. However, the commonly used automated sphygmomanometers have limited accuracy in patients with atrial fibrillation. Consequently, these patients are often underdiagnosed. We present a case of a 73-year-old man with a medical history of atrial fibrillation, peripheral artery disease, and CABG surgery four months before the current event, who came to the emergency department due to progressive dyspnea. The initial diagnostic management showed a large circulatory pericardial effusion, so the patient was admitted to the coronary care unit and underwent pericardial drainage. In the following days, due to a sudden high increase in cardiac troponin, the patient underwent an urgent coronary angiography, which revealed severe left SAS with functional CABG, indicating the occurrence of CSSS. Percutaneous transluminal angioplasty was then performed with an optimal angiographic result. The patient was discharged in good condition with adequate medicament therapy and instructions. This case report highlights atrial fibrillation as a contributing factor for the diagnosis of CSSS and pericardial tamponade after CABG surgery. Furthermore, we suggest a diagnostic approach that can reduce the incidence of both these severe complications.

A multicentre, prospective, randomised controlled trial to assess the safety and effectiveness of cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction: the COOL AMI EU Pivotal Trial.

BACKGROUND: Despite primary PCI (PPCI), ST-elevation myocardial infarction (STEMI) can still result in large infarct size (IS). New technology with rapid intravascular cooling showed positive signals for reduction in IS in anterior STEMI. AIMS: We investigated the effectiveness and safety of rapid systemic intravascular hypothermia as an adjunct to PPCI in conscious patients, with anterior STEMI, without cardiac arrest. METHODS: Hypothermia was induced using the ZOLL® Proteus™ intravascular cooling system. After randomisation of 111 patients, 58 to hypothermia and 53 to control groups, the study was prematurely discontinued by the sponsor due to inconsistent patient logistics between the groups resulting in significantly longer total ischaemic delay in the hypothermia group (232 vs 188 minutes; p<0.001). RESULTS: There were no differences in angiographic features and PPCI result between the groups. Intravascular temperature at wire crossing was 33.3+0.9°C. Infarct size/left ventricular (IS/LV) mass by cardiac magnetic resonance (CMR) at day 4-6 was 21.3% in the hypothermia group and 20.0% in the control group (p=0.540). Major adverse cardiac events at 30 days increased non-significantly in the hypothermia group (8.6% vs 1.9%; p=0.117) while cardiogenic shock (10.3% vs 0%; p=0.028) and paroxysmal atrial fibrillation (43.1% vs 3.8%; p<0.001) were significantly more frequent in the hypothermia group. CONCLUSIONS: The ZOLL Proteus intravascular cooling system reduced temperature to 33.3°C before PPCI in patients with anterior STEMI. Due to inconsistent patient logistics between the groups, this hypothermia protocol resulted in a longer ischaemic delay, did not reduce IS/LV mass and was associated with increased adverse events.

Transcatheter Aortic Valve Implantation Induces Transient Drop in Platelet Reactivity.

ABSTRACT: Although recent studies described platelet reactivity (PR) changes in days after transcatheter aortic valve implantation (TAVI), precise time course and duration of these changes have not been fully investigated. The aim of this study was to investigate PR pattern during and after TAVI in multiple time points. Study included 40 consecutive patients undergoing TAVI. All patients underwent the procedure on dual antiplatelet therapy. PR was measured in 7 time points: before induction of anesthesia (T1), after heparin administration (T2), 10 minutes after initial valve implantation (T3), at the end of procedure (T4), and on 3rd, 6th, and 30th postoperative day (T5-T7). PR was measured using impedance aggregometer using 3 different platelet aggregation agonists (arachidonic acid in ASPItest, adenosine diphosphate in ADPtest and thrombin receptor activating peptide 6 in TRAPtest). All patients underwent successful TAVI procedure. Mean PR on T1 was 22.9 ± 23.0 U for ASPItest, 40.5 ± 23.7 U for ADPtest and 91.7 ± 32.5 U for TRAPtest. There was no significant difference in PR on T2. On T3, significant reduction of PR in all 3 tests was observed [ASPI 10.4 ± 11.6 U (P = 0.001), ADP 24.2 ± 14.1 U (P < 0.001) and TRAP 69.3 ± 26.6 U (P < 0.001)]. PR nadir for all tests was reached on T5, with subsequent PR incline. PR values in all tests returned to baseline levels on T7. Our results show that successful TAVI procedure induces transient decrease in PR regardless of the platelet activation pathway.

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.

Global and regional myocardial function and outcomes after transcatheter aortic valve implantation for aortic stenosis and preserved ejection fraction.

AIM: To investigate the effects of transcatheter aortic valve implantation (TAVI) on early recovery of global and segmental myocardial function in patients with severe symptomatic aortic stenosis and preserved left ventricular ejection fraction (LVEF) and to determine if parameters of deformation correlate with outcomes. METHODS: The echocardiographic (strain analysis) and outcome (hospitalizations because of heart failure and mortality) data of 62 consecutive patients with preserved LVEF (64.54 ±â€Š7.97%) who underwent CoreValve prosthesis implantation were examined. RESULTS: Early after TAVI (5 ±â€Š3.9 days), no significant changes in LVEF or diastolic function were found, while a significant drop of systolic pulmonary artery pressure (PAP) occurred (42.3 ±â€Š14.9 vs. 38.1 ±â€Š13.9 mmHg, P = 0.028). After TAVI global longitudinal strain (GLS) did not change significantly, whereas significant improvement in global mid-level left ventricular (LV) radial strain (GRS) was found (-16.71 ±â€Š2.42 vs. -17.32 ±â€Š3.25%; P = 0.33; 16.57 ±â€Š6.6 vs. 19.48 ±â€Š5.97%, P = 0.018, respectively). Early significant recovery of longitudinal strain was found in basal lateral and anteroseptal segments (P = 0.038 and 0.048). Regional radial strain at the level of papillary muscles [P = 0.038 mid-lateral, P < 0.001 mid-anteroseptum (RSAS)] also improved. There was a significant LV mass index reduction in the late follow-up (152.42 ±â€Š53.21 vs. 136.24 ±â€Š56.67 g/m, P = 0.04). Mean follow-up period was 3.5 ±â€Š1.9 years. Parameters associated with worse outcomes in univariable analysis were RSAS pre-TAVI, LV end-diastolic diameter after TAVI, relative wall thickness, and mitral E and E/A after TAVI. CONCLUSION: Global and regional indices of myocardial function improved early after TAVI, suggesting the potential of myocardium to recover with a reduced risk for clinical deterioration.

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.

Frequency of radial artery anatomic variations in patients undergoing transradial heart catheterization.

Over the last ten years, transradial cardiac catheterization has been increasingly applied, primarily because of its lower incidence of complications compared to the femoral approach. However, one of the greatest flaws of the transradial approach is a relatively high incidence of catheterization failure (1%-5%). Anatomic variations of radial artery are ranked second among the reasons for this. Previous studies have not provided unambiguous data on the frequency of these anomalies. It was therefore the aim of this study to determine the frequency of anatomic variations using routine angiographies of radial artery during left heart catheterization. This was a retrospective study involving examination of 602 images of routine angiographies of radial artery performed during cardiac catheterization. The frequency of anatomic variations of radial artery was 8.8%, exclusive of tortuosities with a frequency of 12.7%. The most frequent anatomic variation was the high origin of radial artery, found in 31 (5.1%) subjects. Radioulnar loops, being one of the potential contraindications for the procedure, were reported in 2% of cases. Regression analysis revealed that age (p < 0.001), female sex (p = 0.015) and high origin (p = 0.034) considerably contributed to the development of tortuosity. The results indicated the incidence of tortuosity to increase linearly with age. Although it is not a contraindication for continuing with the procedure, we recommend that elderly patients have angiography of radial artery performed at the beginning of the procedure due to the higher frequency of tortuosity.

Drug-eluting balloons in patients with non-ST elevation acute coronary syndrome.

BACKGROUND: We compared efficacy of bare-metal stent (BMS) and drug-eluting balloon (DEB) combination vs BMS alone, in patients with non-ST elevation acute coronary syndrome treated with percutaneous coronary intervention (PCI). METHODS: Patients with non-ST elevation myocardial infarction (NSTEMI) or unstable angina (UA) were randomized to BMS only or BMS+DEB group. Angiographic follow-up was performed after 6 months. The primary endpoints were binary in-stent restenosis (ISR) and late lumen loss (LLL) and the secondary endpoints were target lesion revascularization (TLR), stent thrombosis (ST), and new acute coronary syndrome (ACS). RESULTS: A total of 85 patients were enrolled, 44 (BMS) and 41 (BMS+DEB). The median age was 67 (36-84) years and 68 (80%) were male. Fifty-two patients (61.2%) had NSTEMI and 33 patients (38.8%) UA. There was no difference in patient demographics, risk factors, and clinical characteristics, except for more smokers in the BMS+DEB group 18/41 (43.9%) vs 9/44 (20.5%). At follow-up, no significant difference in binary ISR was found; p=0.593, but LLL was significantly lower in the BMS+DEB group 0.68 (0.00-2.15) mm vs 0.22 (0.00-2.35) mm; p=0.002. The difference in major adverse cardiac events (MACE) rate combining TLR, ST, and ACS, between the groups was also non-significant, 29.5% (BMS) vs 24.4% (BMS+DEB); p=0.835. One patient had a subacute ST (BMS+DEB) due to clopidogrel resistance. CONCLUSION: Patients treated with BMS+DEB combination for non-ST elevation acute coronary syndrome had significantly less LLL in comparison to patients treated with BMS alone but without an impact on patient clinical outcomes.

Five-year angiographic and clinical follow-up of patients with drug-eluting stent implantation for symptomatic myocardial bridging in absence of coronary atherosclerotic disease.

OBJECTIVES: The objective of this study was to determine the long-term efficacy and dynamics of systolic and diastolic luminal changes within the bridged segments of coronary arteries after intracoronary stenting with drug-eluting stent (DES) in patients (pts) with symptomatic myocardial bridging (SMB) in the absence of coronary atherosclerosis. BACKGROUND: Although myocardial bridging (MB) represents a benign disease in the majority of pts, in its severest forms it is clinically manifested as typical or atypical angina, myocardial ischemia, myocardial infarction, left ventricular dysfunction, atrioventricular conduction disturbance, exercise-induced ventricular tachycardia, or sudden death. The only existing prospective study of 11 pts with SMB treated with bare-metal stent (BMS) reported a 36% in-stent restenosis (ISR) rate at 7 weeks repeated quantitative coronary angiography (QCA). METHODS: The study consisted of 15 consecutive patients (13 men and 2 women) with SMB of the mid-portion of the left anterior descending (LAD) coronary artery (and in 1 patient, concomitant MB of the left circumflex [LCX] coronary artery) and luminal diameter systolic narrowing of the tunneled segment of ≥50%, underwent percutaneous coronary intervention with DES. Clinical and non-invasive assessments of myocardial ischemia were determined every 6 months over 5 years and QCA was performed 12 and 24 months post procedure if not urged differently by deterioration of clinical symptoms and/or presence of positive ischemia tests. The minimal systolic and diastolic luminal diameters of the bridged/stented segments were measured before, immediately after, and 12 and 24 months post procedure by two independent observers blinded to each other's readings, using QCA commercial software. The endpoints of the study were ISR, target lesion revascularization (TLR) rate, in-stent diameter late luminal loss (LLL), and permanent disappearance or significant improvement of clinical symptoms. RESULTS: After 12 months, ISR and TLR in 16 treated vessels was 18.7%, LLL was 0.2 ± 0.6 mm and permanent disappearance or significant improvement of symptoms was achieved in all 15 pts. In 3 pts, clinically-driven repeat revascularization was necessary within the first 6 months. In 1 patient, coronary perforation complicated stent deployment and was immediately resolved by stent-graft implantation, followed by completely uneventful recovery. CONCLUSIONS: DES implantation in pts with SMB resistant to medical treatment results in prompt and long-term increase of systolic and diastolic luminal diameters, and long-lasting relief of clinical symptoms. Compared to BMS, stenting of SMB with DES resulted in significantly lower ISR and TLR rate.

The impact of successful manual thrombus aspiration on in-stent restenosis after primary PCI: angiographic and clinical follow-up.

OBJECTIVES: This study sought to investigate the impact of successful manual thrombus aspiration on angiographic in-stent restenosis and clinical outcome in patients treated by bare metal stent implantation for ST-segment elevation acute myocardial infarction. BACKGROUND: There are very limited data on the impact of manual thrombus aspiration on the occurrence of in-stent restenosis after bare metal stent implantation. METHODS: This was a prospective, randomized, single-center study. Patients (N=60) presenting within 12 h of ST-segment elevation acute myocardial infarction symptom onset were randomized to primary percutaneous coronary intervention (PCI) with (N=30) or without (N=30) upfront manual thrombus aspiration using the Export aspiration catheter. All patients underwent control coronary angiography after 6 months. RESULTS: Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. Patients who underwent successful manual thrombus aspiration had significantly higher minimal lumen diameter after 6 months (2.25±0.90 vs. 1.63±0.76, P=0.005), significantly lower percentage diameter stenosis (28.81 vs. 45.03%, P=0.017), and significantly lower late lumen loss (0.73±0.84 vs. 1.18±0.79, P=0.035). There was a trend for lower rate of major adverse cardiocerebrovascular events such as death, myocardial reinfarction, stroke, and target lesion revascularization in the same group of patients (16.67 vs. 26.67%, P=0.347). CONCLUSION: Successful upfront manual thrombus aspiration during primary PCI showed beneficial effects on the reduction of in-stent restenosis after bare metal stent implantation compared with standard PCI.

Correlation of femoral intima-media thickness and the severity of coronary artery disease.

The carotid artery intima-media thickness (IMT) is an established surrogate marker of vascular risk. We assessed the common femoral artery IMT and its correlation with coronary artery disease (CAD). We also assessed the influence of vascular risk factors on the femoral IMT. Patients (n = 180; mean age 60.4 ± 10.5 years) who had undergone coronary angiography due to symptoms of CAD were enrolled in this study. We found significantly higher values of femoral IMT in patients with CAD than in those without CAD (P = .0000). A strong positive correlation between femoral IMT and the severity of CAD expressed by the Gensini Score (P = .0000) was observed. There was a positive correlation between femoral IMT and levels of triglycerides (P = .017), body mass index (BMI; P = .036), male gender (P = .0000), and smoking (P = .028). There was a negative correlation between femoral IMT and the level of high-density lipoprotein-cholesterol (P = .001). Femoral IMT could be a novel cardiovascular risk marker.

Apical ballooning syndrome and myocardial bridging in the patient presenting with pulmonary edema.

The apical ballooning syndrome is a relatively rare and underrecognized transient cardiomyopathy precipitated by emotional or physical stress. The role of myocardial bridging in its cause is unknown and extremely rarely reported. We present a case of a 68-year-old woman with apical ballooning syndrome and transient myocardial bridging of the left anterior descending coronary artery, clinically manifested as pulmonary edema. Ischemic ECG changes and mild elevation of cardiac biomarkers were present. She recovered well on medical treatment, and follow-up echocardiography revealed complete recovery of the left ventricular systolic function, whereas repeated coronary angiography after 1 year showed no signs of myocardial bridging. To the best of our knowledge, this is the first report of transient myocardial bridging in a patient with Takotsubo cardiomyopathy with documented normalization of the left ventriculogram and disappearance of left anterior descending coronary artery myocardial bridging.

Spontaneous and catheter-induced secondary coronary artery dissection: a single-centre experience.

6497 consecutive patients who underwent coronary angiography in our institution in a three-year period were analysed. Spontaneous coronary artery dissection was noted in five, and unexpected dissection secondary to coronary arteriography in three patients. All patients with spontaneous dissection presented clinically as myocardial infarction. Three patients (two of them with spontaneous dissection) underwent urgent coronary artery bypass grafting. Percutaneous coronary intervention was successful in two patients with spontaneous and in one with unexpected secondary dissection. One patient with spontaneous and one with secondary dissection were treated medically after failed intervention. In conclusion, spontaneous coronary artery dissection is rare, but not exceptional. Its true incidence might have been underestimated before the advent of coronary interventions in acute myocardial infarction. Survival of all our patients, in contrast to earlier reports on mortality rates up to 50%, may be attributed to the benefits of modern surgery and interventional cardiology.

Primary malignant fibrous histiocytoma of the heart with skeletal muscles metastases.

Malignant fibrous histiocytoma is an extremely rare primary malignant tumor of the heart. It is usually diagnosed when it is locally aggressive or has already metastasized. The prognosis is poor with an average survival time of one year. We report a case of recurrent left atrial malignant fibrous histiocytoma initially misdiagnosed as myxoma. The patient underwent repeated surgical resections followed by chemotherapy. Despite adjuvant chemotherapy, 18 months after initial diagnosis, definitive tumor relapse in left atrium was diagnosed. This is the 48th case of primary cardiac fibrous malignant histiocytoma reported in the literature.

Primary cardiac lymphoma presenting as atrial flutter and total heart block.

Primary cardiac lymphoma is extremely rare. We present the case of a 70-year-old man with primary cardiac lymphoma involving interatrial septum, presenting as atrial flutter and total heart block. The diagnosis was obtained by echocardiography-guided transvenous endocardial biopsy which revealed diffuse large B-cell non-Hodgkin's lymphoma, CD 20+. After six courses of immunochemotherapy the patient achieved complete remission. After 2 months he developed a series of epileptic attacks. Intracerebral lymphoma extension was diagnosed. Two cycles of high-dose methotrexate and cranial irradiation were applied, resulting in a second complete remission.