The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.

Summary Although many case reports and observational studies have reported a correlation between iron deficiency anaemia (IDA) and thrombotic events, the mechanism for this is poorly understood. To evaluate this, we examined the change in coagulability in patients receiving treatment for IDA. Adult patients with IDA were recruited for this study and treated with intravenous iron. The change in coagulability was assessed by thrombin generation using the calibrated automated thrombogram method. The change in factor VIII (FVIII) activity was later examined as a possible link. Forty‐eight participants received intravenous iron and were included in this study. After treatment with intravenous iron, endogenous thrombin potential and peak height decreased in IDA patients by a mean of 122·4 nmol/l/min (95% confidence interval [CI]: 17·9–227, P = 0·023) and 51·9 (95% CI: 26·6–77·2, P < 0·001) respectively. Time to peak (peak time) increased by a mean of 23·6 s (95% CI: 5·4–41·9, P = 0·012). FVIII activity was reduced by a mean of 9·6% (95% CI: 2·54–16·7, P = 0·009). In conclusion, treating IDA reduces the blood's coagulability, as evidenced by the change in thrombin generation and FVIII activity levels. No correlation was found between the degree of iron deficiency correction and thrombogram parameters.

Background Guidelines recommend venous thromboembolism (VTE) prophylaxis in hospitalized medical patients with Padua prediction score (PPS) ≥4 points. This recommendation is based on the high risk of symptomatic VTE observed among these patients in the Italian PPS derivation study, and the fivefold risk reduction with VTE-prophylaxis. This study aims to assess the incidence of VTE in high risk medical patients in a medium sized hospital in Israel. Method In this retrospective cohort study, data was collected of all medical patients hospitalized between January and June 2014. Patients were classified into low and high risk groups according to their PPS score, and according to whether they received anticoagulant thromboprophylaxis for VTE. Patients were further randomly selected to compare high risk patients that did or did not receive anticoagulant thromboprophylaxis. We further compared VTE incidence in high and low risk patients not treated with thromboprophylaxis. A search was conducted for diagnoses of venous thromboembolism and death during hospitalization and the following 90 days. Results 568 high risk patients (PPS ≥4 points) were included, 284 treated with prophylactic anticoagulation and 284 not. There were no VTE events in either group. There was no difference in mortality. A total of 642 non anticoagulated patients were randomly selected, 474 low risk and 168 high risk. There were no VTE events in either group. Conclusions The risk of VTE appears to be very low in our study, suggesting that among medical patients with PPS ≥4, the risk of VTE may differ dramatically between populations.

Background Thrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity.

Thrombin plays a central role in sepsis pathophysiology. The correlation of thrombin generation (TG) assays with infection severity and prognosis, and whether it can be used as a clinical tool, have been poorly explored and are the subjects of our research. We recruited 130 patients with systemic infection between 2016 and 2019. Patients were divided according to infection severity by using the sequential organ failure assessment (SOFA) and quickSOFA (qSOFA) scores. The hemostatic state was analyzed by Calibrated Automated Thrombogram. The primary end points were TG values and the secondary end point was in-hospital mortality. Patients with qSOFA ≥ 2 had a longer lag time (5.6 vs. 4.6 min) and time to peak (8 vs. 6.9 min) than those with lower scores (p = 0.014 and 0.01, respectively). SOFA ≥ 2 had a longer lag time (5.2 vs. 4.3 min), time to peak (7.5 vs. 6.7 min) and lower endogenous thrombin potential (ETP) (1834 vs. 2015 nM*min), p = 0.008, 0.019, and 0.048, respectively. Patients who died (11) had lower ETP (1648 vs. 1928 nM*min) and peak height (284 vs. 345 nM), p = 0.034 and 0.012, respectively. In conclusion TG assays may be a valuable tool in predicting infection severity and prognosis.