Transthoracic ultrasound; seeking the heart in a patient with a large left-sided cirrhotic hydrothorax.

A case of a patient with liver cirrhosis and a large left-sided pleural effusion displacing the heart rightward is presented and the best views to acquire images enabling evaluation of the cardiac function are highlighted. Understanding the modified intrathoracic anatomy in patients with pleural effusions enables quick and focused assessment and can shorten evaluation time while preserving high image quality.

EURObservational Research Programme: the Chronic Ischaemic Cardiovascular Disease Registry: Pilot phase (CICD-PILOT).

AIMS: Chronic ischaemic cardiovascular disease (CICD) is a major cause of mortality and morbidity worldwide. The primary objective of the CICD-Pilot registry was to describe the clinical characteristics and management modalities across Europe in a broad spectrum of patients with CICD. METHODS AND RESULTS: The CICD-Pilot registry is an international prospective observational longitudinal registry, conducted in 100 centres from 10 countries selected to reflect the diversity of health systems and care attitudes across Europe. From April 2013 to December 2014, 2420 consecutive CICD patients with non-ST-elevation acute coronary syndrome (n = 755) and chronic stable coronary artery disease (n = 1464), of whom 933 (63.7%) were planned for elective coronary intervention, or with peripheral artery disease (PAD) (n = 201), were enrolled (30.5% female patients). Mean age was 66.6 ± 10.9 years. The following risk factors were reported: smoking 54.6%, diabetes mellitus 29.2%, hypertension 82.6%, and hypercholesterolaemia 74.1%. Assessment of cardiac function was made in 69.5% and an exercise stress test in 21.2% during/within 1 year preceding admission. New stress imaging modalities were applied in a minority of patients. A marked increase was observed at discharge in the rate of prescription of angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers (82.8%), beta-blockers (80.2%), statins (92.7%), aspirin (90.3%), and clopidogrel (66.8%). Marked differences in clinical profile and treatment modalities were observed across the four cohorts. CONCLUSION: The CICD-Pilot registry suggests that implementation of guideline-recommended therapies has improved since the previous surveys but that important heterogeneity exists in the clinical profile and treatment modalities in the different cohorts of patients enrolled with a broad spectrum of CICDs.

Predictive role of stress echocardiography before carotid endarterectomy in patients with coronary artery disease.

OBJECTIVES: Our aim was to examine the predictive value of preoperative stress echocardiography regarding early myocardial ischemia and late cardiac events after carotid endarterectomy (CEA). METHODS: Patients with coronary artery disease undergoing CEA were prospectively included in this study. All patients (n = 162) were classified into low, medium, and high cardiac risk group, according to preoperative stress echocardiography. Classification was based on the criteria of the American Society of Echocardiography. For all patients, cTnI was measured before surgery and on postoperative days 1, 3, and 7. Postoperative cTnI values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. Cardiac damage was defined as either myocardial ischemia or infarction. RESULTS: No deaths, strokes, or symptomatic coronary events were observed during the early postoperative period. There were 112 low cardiac risk patients, 42 medium-risk patients, and 8 high-risk patients, according to stress echocardiography findings. Overall, there were 22 patients (14%) that increased their cTnI values postoperatively (12 of low cardiac risk and 10 of medium cardiac risk), and all of them were asymptomatic. None of the high-risk patients showed any troponin increase. Late cardiac events were associated with cTnI increase, although no high-risk patients showed any late event. CONCLUSIONS: Preoperative stress echocardiography does not seem to independently recognize patients in high risk for asymptomatic cardiac damage after CEA. Postoperative troponin elevation seems to be more predictive for late adverse cardiac events than preoperative stress echocardiography.

Evaluation of apoptosis in varicose vein disease complicated by superficial vein thrombosis.

BACKGROUND: The factors contributing to superficial vein thrombosis (SVT) in patients with varicose vein disease are unclear. Differences in vein wall apoptotic activity could be associated with the pathogenesis of SVT. The aim of the study is to address the role of the programmed cell death in the vein wall by comparing varicose veins with history of SVT to uncomplicated varicose veins. PATIENTS AND METHODS: Vein segments from the proximal part of the great saphenous vein (GSV), the distal part of the vein and from a varicose tributary, from 16 patients with varicose vein disease and one episode of SVT, were evaluated for the immunohistochemical expression of pro-apoptotic (Bax, p53, Caspase 3, BCL-6, BCL-xs), anti-apoptotic (BCL-xl and BCL-2) and proliferation (Ki-67) markers. The results of this study were compared to the results from the evaluation of 19 patients suffering from uncomplicated varicose vein disease and 10 healthy GSVs as controls. RESULTS: Overall, there was increased apoptosis in the distal part of GSV compared to the proximal part documented by increased expression of Bax (p < 0.01), Caspase 3 (p = 0.01), BCL-xs (p < 0.01). The comparisons of the markers' expression between patients with varicose veins and patients with a history of SVT showed significant differences among the three different anatomic locations. In the proximal GSV, only BCL-xs was higher in patients with SVT (p = 0.029). In the tributaries, Bax, BCL-xl and Ki-67 were higher in patients with SVT (p < 0.01). In the distal GSV, increased Bax, BCL-xs, BCL-xl and Ki-67 staining was observed in the thrombosis group compared to uncomplicated veins (p < 0.01). CONCLUSIONS: The vein wall in SVT shows increased pro-apoptotic activity compared to uncomplicated disease and normal veins. Whether increased vein wall cell apoptosis is a causative factor for SVT in varicose veins disease or a repairing mechanism of the thrombosis itself needs further research.

Long-Term Outcomes of Aortic Stenosis Patients with Different Flow/Gradient Patterns Undergoing Transcatheter Aortic Valve Implantation.

Background: Few data exist on the comparative long-term outcomes of severe aortic stenosis (AS) patients with different flow-gradient patterns undergoing transcatheter aortic valve implantation (TAVI). This study sought to evaluate the impact of the pre-TAVI flow-gradient pattern on long-term clinical outcomes after TAVI and assess changes in the left ventricular ejection fraction (LVEF) of different subtypes of AS patients following TAVI. Methods: Consecutive patients with severe AS undergoing TAVI in our institution were screened and prospectively enrolled. Patients were divided into four subgroups according to pre-TAVI flow/gradient pattern: (i) low flow-low gradient (LF-LG): stroke volume indexed (SVi) ≤ 35 mL/m2 and mean gradient (MG) < 40 mmHg); (ii) normal flow-low gradient (NF-LG): SVi > 35 mL/m2 and MG < 40 mmHg; (iii) low flow-high gradient (LF-HG): Svi 35 mL/m2 and MG ≥ 40 mmHg and (iv) normal flow-high gradient (NF-HG): SVi > 35 mL/m2 and MG ≥ 40 mmHg. Transthoracic echocardiography was repeated at 1-year follow-up. Clinical follow-up was obtained at 12 months, and yearly thereafter until 5-year follow-up was complete for all patients. Results: A total of 272 patients with complete echocardiographic and clinical follow-up were included in our analysis. Their mean age was 80 ± 7 years and the majority of patients (N = 138, 50.8%) were women. 62 patients (22.8% of the study population) were distributed in the LF-LG group, 98 patients (36%) were LF-HG patients, 95 patients (34.9%) were NF-HG, and 17 patients (6.3%) were NF-LG. There was a greater prevalence of comorbidities among LF-LG AS patients. One-year all-cause mortality differed significantly between the four subgroups of AS patients (log-rank p: 0.022) and was more prevalent among LF-LG patients (25.8%) compared to LF-HG (11.3%), NF-HG (6.3%) and NF-LG patients (18.8%). At 5-year follow-up, global mortality remained persistently higher among LF-LG patients (64.5%) compared to LF-HG (47.9%), NF-HG (42.9%), and NF-LG patients (58.8%) (log-rank p: 0.029). At multivariable Cox hazard regression analysis, baseline SVi (HR: 0.951, 95% C.I.; 0.918-0.984), the presence of at least moderate tricuspid regurgitation at baseline (HR: 3.091, 95% C.I: 1.645-5.809) and at least moderate paravalvular leak (PVL) post-TAVI (HR: 1.456, 95% C.I.: 1.106-1.792) were significant independent predictors of late global mortality. LF-LG patients and LF-HG patients exhibited a significant increase in LVEF at 1-year follow-up. A lower LVEF (p < 0.001) and a lower Svi (p < 0.001) at baseline were associated with LVEF improvement at 1-year. Conclusions: Patients with LF-LG AS have acceptable 1-year outcomes with significant improvement in LVEF at 1-year follow-up, but exhibit exceedingly high 5-year mortality following TAVI. The presence of low transvalvular flow and at least moderate tricuspid regurgitation at baseline and significant paravalvular leak post-TAVI were associated with poorer long-term outcomes in the entire cohort of AS patients. The presence of a low LVEF or a low SVi predicts LVEF improvement at 1-year.

Electro-Mechanical Alterations in Atrial Fibrillation: Structural, Electrical, and Functional Correlates.

Atrial fibrillation is the most common arrhythmia encountered in clinical practice affecting both patients' survival and well-being. Apart from aging, many cardiovascular risk factors may cause structural remodeling of the atrial myocardium leading to atrial fibrillation development. Structural remodelling refers to the development of atrial fibrosis, as well as to alterations in atrial size and cellular ultrastructure. The latter includes myolysis, the development of glycogen accumulation, altered Connexin expression, subcellular changes, and sinus rhythm alterations. The structural remodeling of the atrial myocardium is commonly associated with the presence of interatrial block. On the other hand, prolongation of the interatrial conduction time is encountered when atrial pressure is acutely increased. Electrical correlates of conduction disturbances include alterations in P wave parameters, such as partial or advanced interatrial block, alterations in P wave axis, voltage, area, morphology, or abnormal electrophysiological characteristics, such as alterations in bipolar or unipolar voltage mapping, electrogram fractionation, endo-epicardial asynchrony of the atrial wall, or slower cardiac conduction velocity. Functional correlates of conduction disturbances may incorporate alterations in left atrial diameter, volume, or strain. Echocardiography or cardiac magnetic resonance imaging (MRI) is commonly used to assess these parameters. Finally, the echocardiography-derived total atrial conduction time (PA-TDI duration) may reflect both atrial electrical and structural alterations.

Direct Oral Anticoagulants use in Patients with Stable Coronary Artery Disease, Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

The investigation for the optimal anticoagulation strategy for patients with stable coronary artery disease, acute coronary syndromes, and undergoing percutaneous coronary intervention constitutes a great challenge for physicians and is a field of extensive research. Although aspirin is commonly recommended as a protective measure for all patients with coronary artery disease and dual antiplatelet therapy for those undergoing procedures, such as percutaneous coronary intervention or coronary artery bypass graft surgery, the risk of recurrent cardiovascular events remains significant. In this context, the shortcomings associated with the use of vitamin K antagonists have led to the assessment of direct oral anticoagulants as promising alternatives. This review will explore and provide a comprehensive analysis of the existing data regarding the use of direct oral anticoagulants in patients with stable coronary artery disease or acute coronary syndrome, as well as their effectiveness in those undergoing percutaneous coronary intervention or coronary artery bypass graft surgery.

Adhesion Molecules as Prognostic Biomarkers in Coronary Artery Disease.

Atherosclerosis is a progressive disease, culminating in the production of atherosclerotic plaques in arteries through intricate pathophysiological processes. The progression of this disorder is based on the effect of triggering factors -mainly hyperlipidemia, diabetes mellitus, arterial hypertension, and smoking- on the endothelium. Coronary artery disease (CAD) is an atherosclerotic disease with a higher prevalence among individuals. Pro- and anti-inflammatory cytokines are the main contributors to atherosclerotic plaque formation. CAD and its manifestations multifactorial affect patients' quality of life, burdening the global healthcare system. Recently, the role of adhesion molecules in CAD progression has been recognized. Physicians delve into the pathophysiologic basis of CAD progression, focusing on the effect of adhesion molecules. They are proteins that mediate cell-cell and cell-extracellular matrix interaction and adhesion, driving the formation of atherosclerotic plaques. Several studies have assessed their role in atherosclerotic disease in small cohorts and in experimental animal models as well. Furthermore, several agents, such as nanoparticles, have been introduced modifying the main atherosclerotic risk factors as well as targeting the endothelial inflammatory response and atherosclerotic plaque stabilization. In this review, we discuss the role of adhesion molecules in atherosclerosis and CAD progression, as well as the potential to be used as targeting moieties for individualized treatment.

Impact of Evolution of Self-Expandable Aortic Valve Design: Peri-Operative and Short-Term Outcomes.

A few data exist on the differences of implantable aortic valve bio-prostheses. We investigate three generations of self-expandable aortic valves in terms of the outcomes. Patients undergoing transcatheter aortic valve implantation (TAVI) were allocated into three groups according to the valve type: group A (CoreValveTM), group B (EvolutTMR) and group C (EvolutTMPRO). The implantation depth, device success, electrocardiographic parameters, need for permanent pacemaker (PPM), and paravalvular leak (PVL) were assessed. In the study, 129 patients were included. The final implantation depth did not differ among the groups (p = 0.07). CoreValveTM presented greater upward jump of the valve at release (2.88 ± 2.33 mm vs. 1.48 ± 1.09 mm and 1.71 ± 1.35 mm, for groups A, B, and C, respectively, p = 0.011). The device success (at least 98% for all groups, p = 1.00) and PVL rates (67% vs. 58%, vs. 60% for groups A, B, and C, respectively, p = 0.64) did not differ. PPM implantation within 24 h (33% vs. 19% vs. 7% for groups A, B, and C, respectively, p = 0.006) and until discharge (group A: 38% vs. group B: 19% and group C: 9%, p = 0.005) was lower in the newer generation valves. Newer generation valves present better device positioning, more predictable deployment, and fewer rates of PPM implantation. No significant difference in PVL was observed.

Effects of Chemotherapy on Aortic 18-Fluorodeoxyglucose Uptake in Patients With Hodgkin and Non-Hodgkin Lymphoma.

Background: Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives: The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods: Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. Results: Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = -0.20, 95% CI: -0.07 to -0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). Conclusions: Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

Contemporary management of pericardial effusion.

Pericardial effusion is a relatively common clinical condition with a variety of clinical manifestations ranging from incidentally discovered asymptomatic cases to life-threatening cardiac tamponade. The etiology encompasses idiopathic cases and forms secondary to different conditions, including autoimmune diseases, malignancies, metabolic disorders, etc. While medical therapy should be offered to patients with elevation of inflammatory markers, in specific forms treatment should be appropriate to the underlying disorder. In cases with hemodynamic compromise pericardial drainage either with pericardiocentesis or pericardial "window" is indicated for therapeutic and diagnostic purposes. In the remainder, factors like comorbidities, size and location of the pericardial effusion will influence the clinical decision making. In asymptomatic or minimally symptomatic chronic large idiopathic pericardial effusions, according to recent evidence, a conservative approach with watchful waiting seems the most reasonable option. The prognosis of pericardial effusions largely depends on the underlying etiologies. Metastatic spread to the pericardium has an ominous prognosis whereas large to moderate effusions have been often associated with known or newly discovered specific underlying causes. Chronic small idiopathic effusions have an excellent prognosis and do not require specific monitoring. Large chronic idiopathic effusions in clinically stable patients require a 3 to 6-month assessment ideally in a specialized unit.

Precision Medicine in Aortic Anastomosis: A Numerical and Experimental Study of a Novel Double-Sided Needle.

BACKGROUND: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess the efficacy of the new design in comparison with the conventional needle. METHODS: A series of simulations were conducted with COMSOL software in order to perform a fatigue comparative analysis between the new and the conventional needle design. Ease of penetration into a piece of polydimethylsiloxane was evaluated. Lastly, the prototype was tested under in-vitro conditions in comparison with the conventional needle. RESULTS: Based on fatigue analysis, the new needle design improves durability, provided the two tips are equally used. The polytetrafluoroethylene coating improves penetration into the tissue by 7% to 17%, while electropolishing improves penetration up to 19%. When using the novel needle design, the average anastomotic task completion time was significantly reduced by 22% and the overall distance of hand movements was significantly reduced by 20%. CONCLUSIONS: The proposed design exhibited a shorter anastomotic time and seems promising in relation to ease of use and simplicity of the anastomotic technique it introduces.

Hypertensive crisis and pulmonary edema following rituximab-induced anaphylaxis.

Rituximab is a monoclonal antibody against the protein CD20. Various lymphomas as well as non-malignant immune disorders are treated with this antibody. Hypersensitivity reactions associated with the use of rituximab include urticaria, hypotension, chest tightness, vomiting, oxygen desaturation and bronchospasm. A very uncommon case of hypertensive crisis and pulmonary edema following rituximab-induced hypersensitivity reaction in an 80-year-old man receiving rituximab for non-Hodgkin lymphoma is reported. Anaphylaxis manifesting as coronary vasospasm following drug treatment, including rituximab, could be proved a serious condition in patients who need specific treatment. In these patients desensitization protocols seem to be mandatory.

Electrocardiographic criteria for detecting coronary artery disease in hypertensive patients with ST-segment changes during exercise testing.

PURPOSE: It is well known that patients with arterial hypertension frequently present with ischemic electrocardiographic changes during exercise testing without actually having coronary artery disease (CAD). The purpose of this study was to establish additional electrocardiographic criteria during exercise testing for detecting CAD in hypertensive patients with ischemic ST-segment response. METHODS: Three hundred eighty-two consecutive hypertensive patients (224 males, 58 +/- 8 years) who presented with ischemic electrocardiographic changes during exercise testing and agreed to undergo coronary arteriography were included in the study. RESULTS: From 382 hypertensive patients undergoing coronary angiography, only 76 (20%) had significant coronary stenosis, whereas 306 (80%) had normal coronary arteries. From 382 patients, 287 (75%) (group A) presented with ST-segment depression during exercise in leads II-III-aVF-V(6), 271 (94%) of which had normal arteries at the angiography. The remaining 95 patients (25%) (group B) of the studied patients presented with ST-segment depression in II-III-aVF and/or V(4) through V(6), 60 (63%) of which had CAD. Furthermore, 251 patients of group A presented with ST-segment depression during the fourth to sixth minute of the recovery period in V(4) through V(6), 247 (98%) of which had normal arteries. Another 28 patients from group B presented with ST-segment depression during the fourth to eighth minute of the recovery period in V(4) through V(6), 22 (79%) of which had significant coronary artery stenosis. CONCLUSIONS: Hypertensive patients who present with ST-segment depression during exercise in leads II-III-aVF and/or V(4) through V(6) and with a prolonged duration of this depression at the recovery phase (fourth to eighth minute) are more likely to have CAD. Absence of ST-segment depression in V(4) and V(5) at the end of exercise or during the seventh and eighth minute of recovery favors a false-positive result.

Biomarkers Determining Prognosis of Atrial Fibrillation Ablation.

Catheter ablation for rhythm control is recommended in specific patient populations with paroxysmal, persistent, or long-standing persistent atrial fibrillation. Pulmonary vein isolation is the cornerstone of the ablative therapy for atrial fibrillation. However, relapse is still common since the single procedure efficacy of atrial fibrillation ablation was estimated to be 60-80% in paroxysmal and 50-70% in persistent atrial fibrillation. It is important to identify predictors of successful atrial fibrillation patients ablation. In the present review, we will assess the role of available biomarkers to predict responders of an initial atrial fibrillation catheter ablation. Emphasis has been given on the role of myocardial injury biomarkers, natriuretic peptides and traditional inflammatory markers. Novel inflammatory markers, oxidative stress biomarkers and microRNAs have also been examined as predictors of a successful atrial fibrillation procedure. Notably, the impact of procedural and short-term administration of steroids, as well as the role of colchicine on preventing atrial fibrillation recurrence after ablation is thoroughly presented.

Assessment of arterial baroreflex sensitivity by different computational analyses of pressure wave signals alone.

BACKGROUND AND OBJECTIVE: Baroreflex sensitivity (BRS) is an important indicator of the functionality of the arterial baroreceptors, and its assessment may have major research and clinical implications. An important requirement for its quantification is the continuous recording of electrocardiography (ECG) signal, so as to extract the RR interval, in parallel with continuous beat-to-beat blood pressure recording. We aimed to accurately calculate the RR Interval from pressure wave recordings per se, namely, the Pulse Interval (PI) using various arterial pulse wave analysis algorithms and to evaluate the precision and accuracy of BRS values calculated with the PI compared to BRS values calculated with the RR Interval. METHODS: We analyzed the open access data of the Eurobavar study, which contains a set of ECG and arterial blood pressure (BP) wave signals recorded at 11 European centers. Pressure waveforms were continuously recorded by the Finapres apparatus which uses a finger cuff. The cuff pressure around the finger is dynamically adjusted by a servo-system to equal intra-arterial pressure, thus allowing the continuous recording of beat-to-beat BP waves. RR Interval was calculated from the ECG, whereas, PI was extracted from the arterial pulse waveforms, using 4 different methods (minimum, maximum, maximum 1st derivative and intersecting tangents method). BRS values were estimated by time domain and frequency domain methods. In order to compare agreement, accuracy, precision, variability, and the association between the reference BRS using the RR Interval and the BRS values using PI, standard statistical methods (i.e. intraclass correlation coefficients, RMSE, regression analysis) and Bland-Altman methods were performed. RESULTS: We found that analysis of pressure waves alone by frequency-based (i.e. spectral) methods, provides the most accurate results of BRS estimation compared to time-domain methods (ICC > 0.9, R > 0.9, RMSE > 0.8 ms/mmHg). Concerning the spectral method, any algorithm for PI calculation is sufficient, as all show excellent agreement with the respective RR-intervals determined by ECG time series. Only the intersecting tangents and the maximum 1st derivative methods for PI calculation produce the most accurate results in time domain BRS estimation. CONCLUSION: BRS estimation by proper analysis of pressure wave signals alone is feasible and accurate. Further studies are needed to investigate the clinical validity and relevance of the different BRS estimations in diagnostic, prognostic and therapeutic levels.

Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation.

BACKGROUND: Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. OBJECTIVES/METHODS: The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. RESULTS: Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. CONCLUSIONS: Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.

Sodium-glucose Cotransporter 2 Inhibitors: Potential Cardiovascular and Mortality Benefits.

BACKGROUND: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease-related death and cardiovascular events associated with HbA1c levels of greater than 7% compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. OBJECTIVES: To summarize data on the potential mechanisms of SGLT-2 inhibition that could exert cardiovascular benefits in patients with diabetes mellitus. METHOD: We conducted an in-depth literature search of SGLT-2 inhibitors and potential cardiovascular benefits and mechanisms that mediate those effects. RESULTS: In diabetes, expression of the SGLT-2 genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening hyperglycemia. SGLT-2 inhibition should offer potential cardiovascular protection in diabetic patients via attenuating hyperglycemia, blood pressure, body weight, hyperuricemia, and diabetic nephropathy. CONCLUSION: The initial data of SGLT-2 inhibitors suggest beneficial effects on cardiovascular risk among patients with diabetes mellitus. Several mechanisms are hypothesized to mediate the abovementioned benefits. Future randomized, controlled studies are needed in order to unveil the contribution of each mechanism to these outcomes.

Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated?

OBJECTIVE: To provide a comprehensive review summarizing the existing evidence on the association between nonalcoholic fatty liver disease (NAFLD) and hypertension (HT) independent of other components of metabolic syndrome. METHODS: We searched the literature through Medline and the Cochrane Library for studies evaluating the relationship between hypertension and fatty liver disease. RESULTS: Studies testing this association are limited, but agree that HT and fatty liver disease are inter-related independent of other components of the metabolic syndrome such as obesity and diabetes mellitus. Clinical evidence shows that NAFLD is associated with new-onset HT, whereas increased blood pressure is related to the development of fatty liver disease and the possible subsequent progression to liver fibrosis. Insulin resistance and activation of the renin-angiotensin-aldosterone system (RAAS) might provide potential pathophysiologic links between these clinical entities. Until further evidence is available, patients with HT should be meticulously evaluated and treated for fatty liver disease and vice versa. RAAS inhibitors have been tested in NAFLD, presenting a favorable profile by decreasing insulin resistance and fibrosis progression. CONCLUSION: NAFLD and HT are associated independent of traditional cardiovascular risk factors. Insulin resistance appears to be the main linking mechanism. Although RAAS inhibitors are the most beneficial treatment option for HT in patients with NAFLD, randomized studies on the administration of these agents in HT patients with NAFDL are warranted to provide optimal treatment options in these high cardiovascular risk individuals.