1,721,017 research outputs found
Gut barrier dysfunction and endotoxemia in heart failure: A dangerous connubium?
No full text: Heart failure (HF) is a leading cause of death worldwide despite recent advances in pharmacological treatments. Gut microbiota dysbiosis and gut barrier dysfunction with consequent bacterial translocation and increased blood endotoxemia has gained much attention as one of the key pathogenetic mechanisms contributing to increased mortality of patients at risk or with cardiovascular disease. Indeed, increased blood levels of lipopolysaccharide (LPS), a glycolipid of outer membrane of gut gram-negative bacteria, have been detected in patients with diabetes, obesity and nonalcoholic fatty liver disease or in patients with established coronary disease such as myocardial infarction or atrial fibrillation, suggesting endotoxemia as aggravating factor via systemic inflammation and eventually vascular damage. Upon interaction with its receptor Toll-like receptor 4 (TLR4) LPS may, in fact, act at different cellular levels so eliciting formation of proinflammatory cytokines or exerting a procoagulant activity. Increasing body of evidence pointed to endotoxemia as factor potentially deteriorating the clinical course of patients with HF, that, in fact, is associated with gut dysbiosis-derived changes of gut barrier functionality and eventually bacteria or bacterial product translocation into systemic circulation. The aim of this review is to summarize current experimental and clinical evidence on the mechanisms linking gut dysbiosis-related endotoxemia with HF, its potential negative impact with HF progression, and the therapeutic strategies that can counteract endotoxemia
Minimizing drug-drug interactions between dabigatran and levetiracetam through clinical management: a case report
Full text linkBACKGROUND: Direct oral anticoagulants (DOACs) are useful for stroke prevention in atrial fibrillation (AF) patients. However, the concomitant administration of Levetiracetam limited their use in clinical practice, although some authors raise doubts about clinical relevance of the interaction. CASE SUMMARY: We report a case of a 54-year-old male with AF, cirrhosis, and seizures, in which the assessment of Dabigatran plasma concentration was needed due to the concomitant use of Levetiracetam. In this case, no relevant reduction of trough Dabigatran plasma concentration was found. An increased peak serum level of dabigatran may be obtained delaying levetiracetam administration. The patient was then followed in our clinic and during 32 months of follow-up no ischaemic or haemorrhagic events occurred. DISCUSSION: The evaluation of DOACs concentration could be helpful to start a tailored therapy in frailty patients
Tailored Practical Management of Patients With Atrial Fibrillation: A Risk Factor-Based Approach
Full text linkThe management of antithrombotic therapy for thromboprophylaxis in patients with atrial fibrillation (AF) has been recently evolved by the progressive replacement of vitamin K antagonists with the non-vitamin K antagonist oral anticoagulants (NOACs). However, while these drugs are effective in reducing ischemic stroke/systemic embolism, a still high rate of cardiovascular events is present in the AF population. A tailored integrated approach to patients with AF is therefore necessary to reduce both thromboembolic events and cardiovascular disease. This approach should consist in the assessment of individual risk factors for ischemic and bleeding events in order to choose the most appropriate anticoagulant treatment according to patient's characteristics and preference. To this purpose, several risk scores have been developed and validated to stratify thromboembolic and hemorrhagic risk. This review provides an individual-based strategy for the management of patients with AF, from a risk-factor based approach to a tailored prescription and monitoring of NOACs. In particular, we reported an updated practical management strategy for AF patients in specific clinical situations such as those (1) experiencing a major bleeding, (2) requiring a switch to another antithrombotic regimen, (3) restarting anticoagulation after acute ischemic stroke, (4) suffering from an acute coronary artery disease (acute coronary syndrome or undergoing cardiac revascularization)
Cancer and atrial fibrillation: Epidemiology, mechanisms, and anticoagulation treatment
No full textCancer patients are at an increased risk of developing atrial fibrillation (AF) and thrombosis. However, the management of anticoagulation in patients with both diseases may be challenging, and data on these patients are lacking. We summarize the current evidence on the incidence and prevalence of cancer in AF and vice versa and provide some practical considerations on the management of oral anticoagulation in specific clinical situations. Low-molecular weight heparins are not approved for thromboprophylaxis in AF, and management of warfarin can be difficult. The use of direct oral anticoagulants may be particularly attractive for their rapid onset/offset action and lower bleeding risk
Acute upper and lower gastrointestinal bleeding management in older people taking or not taking anticoagulants: a literature review
Full text linkAcute upper and lower gastrointestinal (GI) bleeding may be a potentially
life-threatening event that requires prompt recognition and an early effective
management, being responsible for a considerable number of hospital
admissions. Methods. We perform a clinical review to summarize the recent
international guidelines, helping the physician in clinical practice. Older people
are a vulnerable subgroup of patients more prone to developing GI bleeding
because of several comorbidities and polypharmacy, especially related to an
increased use of antiplatelet and anticoagulant drugs. In addition, older patients
may have higher peri-procedural risk that should be evaluated. The recent
introduction of reversal strategies may help the management of GI bleeding
in this subgroup of patients. In this review, we aimed to (1) summarize the
epidemiology and risk factors for upper and lower GI bleeding, (2) describe
treatment options with a focus on pharmacodynamics and pharmacokinetics
of different proton pump inhibitors, and (3) provide an overview of the clinical
management with flowcharts for risk stratification and treatment. In conclusion,
GI is common in older patients and an early effective management may
be helpful in the reduction of several complications
Long-term risk of hospitalization and death in patients with mechanical prosthetic heart valves
No full text: Mechanical prosthetic heart valves (MPHV) are commonly used for valvular heart disease in patients with long life expectancy. Few longitudinal data on hospitalizations specific causes in MPHV patients are available. We investigated the risk of all-cause hospitalization and mortality in MPHV patients. We performed a prospective observational ongoing study including MPHVs consecutive patients referring to the atherothrombosis outpatient clinic of the Policlinico Umberto I of Rome for the vitamin K antagonist (VKA) management. Study endpoints were all-cause, cardiovascular hospitalization and overall mortality. We included 305 MPHV patients (38.4% women, median age 60.2 years). The site of MPHV was aortic in 53.5%, mitral in 29.5% and mitro-aortic in 17%. During a median follow-up of 57.3 months, 142 hospitalizations occurred (8.16 per 100 person-years). The most common causes of hospitalization were cardiovascular disease (3.62 per 100 person-years), infections, surgery and bleeding. Predictors of cardiovascular hospitalization were atrial fibrillation (Hazard ratio [HR] 1.75, 95% confidence interval [95%CI] 1.04-2.95, p= 0.035), previous stroke/transient ischemic attack (HR 2.96, 95%CI 1.59-5.48, p=0.001) and peripheral artery disease (HR 2.42, 95%CI 1.09-5.36, p=0.030). During a median follow-up of 97.2 months, 61 deaths occurred (2.43 per 100 person-years). Age was directly associated with the risk of death (HR 1.088, 95%CI 1.054-1.122, p<0.001), while time in therapeutic range above the median was inversely associated (HR 0.436, 95%CI 0.242-0.786, p= 0.006). In conclusion, MPHV patients had a high incidence of hospitalizations, especially cardiovascular-related. The incidence of death is high, but it may be reduced by maintaining a good quality of anticoagulation
Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease. A comprehensive systematic-review and meta-analysis
Full text linkIntroduction: The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients.Materials and methods: MEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated.Results: 377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83-4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05-7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02-2.77) and G20210A (heterozygous 1.49 95%CI, 1.22-1.82; homozygous 1.54 95%CI, 0.79-2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80-16.43). Specific subgroups with higher PPs and ORs were identified according to age and region. Conclusions: Patients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients
Serum albumin, clotting activation and COVID-19 severity: a systematic review and meta-regression analysis of 4579 patients
Full text linkBACKGROUND: Preliminary data showed that serum albumin (SA), an acute phase protein with anticoagulant property,
is inversely associated with thrombotic complications in respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection
associated disease (COVID-19). We performed a meta-analysis to corroborate this finding on a large sample population.
METHODS: We performed a systematic review and meta-regression analysis of clinical studies reporting data on SA
according to the severity of COVID-19 disease. COVID-19 severity was defined as: 1) admission to the Intensive Care
Unit; 2) acute respiratory distress syndrome; or 3) in-hospital death.
RESULT S: We included 16 studies with 4,579 patients with SARS-CoV-2 infection. Mean age was 51.5 years, and 2146
(44.2%) of patients were women. Overall, 1199 (31.3%) of patients had severe COVID-19 (range 5.4% to 72.6%). Mean
SA level was 37.15 g/L. The pooled analysis showed a mean difference of SA: -4.06 g/L (95% CI -4.98/-3.15) in severe
COVID-19 compared to non-severe ones. This difference ranged from -7.10 g/L to 1.09 g/L. At meta regression analysis,
the difference in SA levels between severe and non-severe COVID-19 patients was more evident in studies with high DDimer
(P<0.001) and procalcitonin (P=0.07), suggesting a more SA reduction in patients with thrombotic/septic disease.
CONCLUSIONS: SA is significantly reduced in severe COVID-19 and associated with elevated D-Dimer. Albumin
supplementation may be tested as adjunctive therapeutic strategy to reduce the thrombotic risk
The Atrial fibrillation Better Care (ABC) pathway and cardiac complications in atrial fibrillation:a potential sex-based difference. The ATHERO-AF study
No full textBACKGROUND: An integrated care approach is recommended to optimize management of patients with atrial fibrillation (AF). The impact of the Atrial fibrillation Better Care (ABC) pathway on major adverse cardiac events (MACE), which are the main causes of death in AF, has not been explored.MATERIAL AND METHODS: We investigated the association between ABC compliance and MACE incidence in 1157 (2690 patient-years) nonvalvular AF patients from the ATHERO-AF study. A subgroup analysis by sex and high cardiovascular risk patients as defined by a 2MACE score ≥3 was performed.RESULTS: Overall, 428 (37%) patients composed the ABC-compliant group. During a median follow up of 23 (IQR 12-37) months, 64 MACE occurred (2.38%/year). Kaplan Meier curve analysis showed a higher rate of MACE in ABC non-compliant group compared to the ABC-compliant (log-rank test p=0.006). The risk of MACE increased by the number of non-fulfilled ABC criteria. On multivariable Cox proportional hazard regression analysis, the ABC non-compliance was associated with an increased risk of MACE (Hazard ratio (HR) 2.244, 95% Confidence Interval (95%CI) 1.129-4.462). Men were more likely to have suboptimal anticoagulation control (group A), while uncontrolled symptoms were more frequent in women. The association between non-ABC and MACE was more evident in men than women (HR 3.647, 95%CI 1.294-10.277) and in patients with 2MACE score ≥3 (HR 1.728, 95%CI 1.209-2.472).CONCLUSION: An integrated care ABC approach is associated with a reduced risk of MACE in the AF population, especially in men and in patients at high risk of MACE.</p
Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding
No full textAnti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B2 and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB2 value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB2 was -6.5% with warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban (p<0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB2 (B: -0.469, p<0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB2 in the NOACs group (Rs: 0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2 excretion compared to warfarin, suggesting that NOACs possess antiplatelet propert
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