BACKGROUND: Although well-known for their thromboresistance, bileaflet mechanical heart valves (BMHV) require lifelong anti-thrombotic therapy. This must be associated with a certain level of thrombogenicity. Since both thromboresistance and thrombogenicity are explained by the blood-artificial surface or liquid-solid interactions, the aim of the present study was to explore BMHV thromboresistance from new perspectives. The wettability of BMHV pyrolytic carbon (PyC) occluders was investigated in under-liquid conditions. The submerged BMHV wettability clarifies the mechanisms involved in the thromboresistance.
METHODS: The PyC occluders of a SJM Regent™ BMHV were previously laser irradiated, to create a surface hierarchical nano-texture, featuring three nano-configurations. Additionally, four PyC occluders of standard BMHV (Carbomedics, SJM Regent™, Bicarbon™, On-X®), were investigated. All occluders were evaluated in under-liquid configuration, with silicon oil used as the working droplet, while water, simulating blood, was used as the surrounding liquid. The under-liquid droplet-substrate wetting interactions were analyzed using contact angle goniometry.
RESULTS: All the standard occluders showed very low contact angle, reflecting a pronounced affinity for non-polar molecules. No receding of the contact line could be observed for the untreated occluders. The smallest static contact angle of around 61° could be observed for On-X® valve (the only valve made of full PyC). The laser-treated occluders strongly repelled oil in underwater conditions. A drastic change in their wetting behaviour was observed depending on the surrounding fluid, displaying a hydrophobic behaviour in the presence of air (as the surrounding medium), and showing instead a hydrophilic nature, when surrounded by water.
CONCLUSIONS: BMHV \"fear\" water and blood. The intrinsic affinity of BMHV for nonpolar fluids can be translated into a tendency to repel polar fluids, such as water and blood. The blood-artificial surface interaction in BMHV is minimized. The contact between blood and BMHV surface is drastically reduced by polar-nonpolar Van der Waals forces. The \"hydro/bloodphobia\" of BMHV is intrinsically related to their chemical composition and their surface energy, thus their material: PyC indeed. Pertaining to thromboresistance, the surface roughness does not play a significant role. Instead, the thromboresistance of BMHV lies in molecular interactions. BMHV wettability can be tuned by altering the surface interface, by means of nanotechnology.

OBJECTIVE: To evaluate whether warfarin targeted at an international normalized ratio of 1.8 (range, 1.5-2.0) after On-X mechanical aortic valve implant is safe for all patients.
METHODS: This prospective, observational clinical registry assessed adverse event rates in adult patients receiving low-dose warfarin (target international normalized ratio, 1.8; range, 1.5-2.0) plus daily aspirin (75-100 mg) during a 5-year period after On-X aortic valve implant. The primary end point is the combined rate of major bleeding, valve thrombosis, and thromboembolism overall and in 4 subgroups. The comparator is the Prospective Randomized On-X Anticoagulation Trial control group patients on standard-dose warfarin (international normalized ratio, 2.0-3.0) plus aspirin 81 milligrams daily.
RESULTS: A total of 510 patients were recruited at 23 centers in the United States, United Kingdom, and Canada between November 2015 and January 2022. This interim analysis includes 229 patients scheduled to complete 5-year follow-up by August 16, 2023. The linearized occurrence rate (in percent per patient-year) of the primary composite end point of major bleeding, valve thrombosis, and thromboembolism is 1.83% compared with 5.39% (95% confidence interval, 4.12%-6.93%) in the comparator group. Results are consistent in clinic-monitored and home-monitored patients and in those at high risk for thromboembolism. Major bleeding and total bleeding were reduced by 87% and 71%, respectively, versus the comparator group, without an increase in thromboembolic events.
CONCLUSIONS: Interim results support the continued safety of the On-X aortic mechanical valve with a target international normalized ratio of 1.8 plus low-dose aspirin through 5 years after implant, with or without home monitoring.

OBJECTIVE: To assess if warfarin targeted to international normalized ratio (INR) 1.8 (range 1.5-2.0) is safe for all patients with an On-X aortic mechanical valve.
METHODS: This prospective, observational registry follows patients receiving warfarin targeted at an INR of 1.8 (range 1.5-2.0) plus daily aspirin (75-100 mg) after On-X aortic valve replacement. The primary end point is a composite of thromboembolism, valve thrombosis and major bleeding. Secondary end points include the individual rates of thromboembolism, valve thrombosis and major bleeding, as well as the composite in subgroups of home or clinic-monitored INR and risk categorization for thromboembolism. The control was the patient group randomized to standard-dose warfarin (INR 2.0-3.0) plus daily aspirin 81 mg from the PROACT trial.
RESULTS: A total of 510 patients were enroled at 23 centres in the UK, USA and Canada. Currently, the median follow-up duration is 3.4 years, and median achieved INR is 1.9. The primary composite end point rate in the low INR patients is 2.31% vs 5.39% (95% confidence interval 4.12-6.93%) per patient-year in the PROACT control group, constituting a 57% reduction. Results are consistent in subgroups of home or clinic-monitored, and high-risk patients, with reductions of 56%, 57% and 57%, respectively. Major and total bleeding are decreased by 85% and 73%, respectively, with similar rates of thromboembolic events. No valve thrombosis occurred.
CONCLUSIONS: Interim results suggest that warfarin targeted at an INR of 1.8 (range 1.5-2.0) plus aspirin is safe and effective in patients with an On-X aortic mechanical valve with or without home INR monitoring.

Optimal first-trimester anticoagulation is still challenging in pregnant women with mechanical heart valves (MHVs) requiring high-dose warfarin. This multicenter prospective study aims to determine the optimal anticoagulation regimens for pregnant patients with MHVs.
All women were allocated to one of three treatment options during first trimester including lone low-molecular-weight heparin (LMWH), combination of LMWH + 2.5 mg warfarin, and LMWH+4 mg warfarin. Primary maternal outcome included a combination of death, thromboembolism, severe bleeding, and need for treatment of mechanical valve thrombosis (MVT). Any fetal loss was determined as primary fetal outcome.
The study included 78 pregnancies in 65 women with MHVs. Primary maternal outcome rate was 44%, 12.5%, 3.5%, respectively. The rates of primary maternal outcome (44 vs 3.5%, P < .001), obstructive MVT (16 vs 0%, P = .04), MVT requiring treatment (28 vs 0%, P = .003), and cerebral embolism (24 vs 3.4%, P = .041) were found to be significantly higher in lone LMWH group compared to LMWH + 4 mg warfarin group. Moreover, the rates of primary maternal outcome (12.5 vs 44%, P = .015) and treatment for MHV thrombus (4.2 vs 28%, P = .049) were significantly lower in LMWH + 2.5 mg warfarin group compared to lone LMWH group. The incidences of fetal loss were 8 (32%) in the lone LMWH group, 8 (33.3%) in LMWH + 2.5 mg warfarin group, and 11 (37.9%) in LMWH + 4 mg warfarin group (P = .890 for 3-group).Warfarin related-embryopathy was not observed in any case.
The combined anticoagulation strategy of LMWH plus low-dose warfarin during the first trimester of pregnancy may result in less maternal complications with comparable fetal outcomes in patients with MHVs.
Low-molecular-weight heparin (LMWH) is thought to be safer for the fetus, however it is suspected to be less protective for the mother. To solve this dilemma, the authors suggested a novel anticoagulation strategy in pregnant women with prosthetic valves. Seventy-eight pregnancies of 65 women (median age 32 [27-35] years) were included in the study. A combination of LMWH and a reduced dose warfarin were associated with low rates of thrombus-related complications in pregnant patients with mechanical heart valves.

Anticoagulation in patients with mechanical heart valves (MHV) is associated with a risk of major bleeding episodes (MBE). In case of MBE, anticoagulant interruption is advocated. However, there is lack of data regarding the thrombo-embolic events (TE) risk associated with anticoagulant interruption. The main objective of the study was to evaluate the rate and risk factors of 6-months of TEs in patients with MHV experiencing MBE. This observational study was conducted over a 13-year period. Adult patients with a MHV presenting with a MBE were included. The main study endpoint was 6-month TEs, defined by clinical TEs or an echocardiographic documented thrombosis, occurring during an ICU stay or within 6-months. Thromboembolic events were recorded at ICU discharge, and 6 months after discharge. Seventy-nine MBEs were analysed, the rate of TEs at 6-months was 19% CI [11-29%]. The only difference of presentation and management between 6-month TEs and free-TE patients was the time without effective anticoagulation (TWA). The Receiver Operator Characteristic curve identified the value of 122 h of TWA as a cut-off. The multivariate analysis identified early bleeding recurrences (OR 3.62, 95% CI [1.07-12.25], p = 0.039), and TWA longer than 122 h (OR 4.24, 95% CI [1.24-14.5], p = 0.021), as independent risk factors for 6-month TEs. A higher rate of TE was associated with anticoagulation interruption longer than 5 days and early bleeding recurrences. However, the management should still be personalized and discussed for each case given the heterogeneity of causes of MBE and possibilities of haemostatic procedures.

A 68-year-old woman with history of aortic valve replacement developed severe heart failure and cardiac arrest. Transesophageal echocardiography and cardiac computed tomography showed mechanical aortic valve thrombosis. Low-dose, ultraslow infusion of tissue-plasminogen activator was performed while the patient was in a critically ill condition, resulting in the improvement of thrombus burden and structural valve deterioration.
UNASSIGNED: Mechanical valve thrombosis can be an underlying mechanism of severe heart failure, in which systemic thrombolytic therapy in a low-dose, ultraslow, and prolonged manner may improve clinical outcomes, even in critically ill patients.

OBJECTIVE: The aim of this study was to investigate the risks and outcomes of patients with long-term oral anticoagulation (OAC) undergoing spine surgery.
METHODS: All patients on long-term OAC who underwent spine surgery between 01/2005 and 06/2015 were included. Data were prospectively collected within our in-house Spine Surgery registry and retrospectively supplemented with patient chart and administrative database information. A 1:1 propensity score-matched group of patients without OAC from the same time interval served as control. Primary outcomes were post-operative bleeding, wound complications and thromboembolic events up to 90 days post-surgery. Secondary outcomes included intraoperative blood loss, length of hospital stay, death and 3-month post-operative patient-rated outcomes.
RESULTS: In comparison with the control group, patients with OAC (n = 332) had a 3.4-fold (95%CI 1.3-9.0) higher risk for post-operative bleeding, whereas the risks for wound complications and thromboembolic events were comparable between groups. The higher bleeding risk was driven by a higher rate of extraspinal haematomas (3.3% vs. 0.6%; p = 0.001), while there was no difference in epidural haematomas and haematoma evacuations. Risk factors for adverse events among patients with OAC were mechanical heart valves, posterior neck surgery, blood loss > 1000 mL, age, female sex, BMI > 30 kg/m2 and post-operative PTT levels. At 3-month follow-up, most patients reported favourable outcomes with no difference between groups.
CONCLUSIONS: Although OAC patients have a higher risk for complications after spine surgery, the risk for major events is low and patients benefit similarly from surgery.

A dramatic rise in cardiac output with a decrease in afterload are the hallmark of hemodynamic variations induced by normal pregnancy, which requires significant cardiac adaptation. Females with rheumatic mitral valve disease who have had a mitral valve replacement in the past are increasingly choosing to become pregnant. Hypercoagulability of pregnancy, problems with anticoagulant therapy along with hemodynamic changes in pregnancy increase the risk of cardiac complications in this subset. There is a paucity of research on the management of problems in patients with cardiac prosthetic valves. We present a case of primigravida with a history of mitral valve replacement, presenting with a stuck valve.
UNASSIGNED: •Pregnancy is a pro-thrombotic state•Pregnancy with a mechanical heart valve has high risk of stuck vale despite adequate anti-coagulation•Management of such high-risk cases must be carried out at a tertiary care center with all facilities•Multi-disciplinary approach is required to deal with pregnant women with mechanical heart valve.

UNASSIGNED: Currently approved direct oral anticoagulants (DOACs) target thrombin or coagulation factor Xa. Administered in fixed doses without routine laboratory monitoring, DOACs have simplified the approach to oral anticoagulation, when previously the choice was limited to vitamin K antagonists (VKAs).
UNASSIGNED: We discuss a) unresolved issues related to optimal use of DOACs and b) new developments including the potential for FXIa inhibitors to be effective and safer anticoagulants.
UNASSIGNED: By simplifying oral anticoagulation, DOACs have facilitated the uptake of anticoagulation. The DOACs are approved for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism, and their indications are expanding to include the prevention of atherothrombosis. DOACs have now replaced vitamin K antagonists (VKAs) for most indications, but not all. DOACs are inferior to VKAs for patients with mechanical heart valves, left ventricular assist device, rheumatic atrial fibrillation, and those with antiphospholipid syndrome, and their safety and efficacy are uncertain in some populations (e.g. advanced renal and liver disease). Impediments to use include concerns for bleeding and cost. The newly developed FXIa and FXIIa inhibitors have the potential to be safer than current anticoagulants, but phase 3 trials are needed to confirm their clinical efficacy and safety.

BACKGROUND: Rheumatic heart disease (RHD) with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires lifelong anticoagulation that could have a particular impact in women in reproductive age.
METHODS: We report data of a prospective observational cohort study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum by Emergency, an Italian Non-Governmental Organization, to evaluate bleeding risk, its associated determinants, and the impact of lifelong anticoagulation in fertile women.
RESULTS: We studied 3647 patients (median age 25.1 years; 53.9% female). During follow-up [median time 1.1 (0.1-1.2) years], we recorded 85 major bleedings (rate 2.16 × 100 pt-years), Major bleedings occurred more frequently among women (64/85 cases, 75.3%; rate 3.0 × 100 pt-years), compared to men (21/85 cases, 24.7%; rate 1.16 × 100 pt-years) (RR 2.6; 95% CI 1.6-4.5; p = 0.0001). Multivariate analysis was performed to identify variables associated with major bleeding, and female sex was the only risk factor significantly associated, whereas aspirin treatment and higher INR target showed a non-significant trend for higher bleeding risk. Thirty-two/85 (37.6%) of major bleedings were metrorrhagias. When we calculate the incidence of major bleedings after the exclusion of gynecological events, no sex differences in the bleeding risk were found (HR 1.3, 95% CI 0.8-2.3; p = 0.3).
CONCLUSIONS: Bleeding risk of young MHV patients on oral anticoagulant therapy is higher among women, mainly due to metrorrhagia. Women in the reproductive life are at high risk for gynecological bleeding when treated with anticoagulants.