Coagulation Disorders and Thrombotic Complications in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with multiple cardiovascular and noncardiovascular comorbidities and risk factors which increase the risk of thrombotic complications, such as atrial fibrillation, chronic kidney disease, arterial hypertension and type 2 diabetes mellitus. Subsequently, thromboembolic risk stratification in this population poses a great challenge. Since date from the large randomized clinical trials mostly include both patients with truly preserved EF, and those with heart failure with mildly reduced ejection fraction, there is an unmet need to characterize the patients with truly preserved EF. Considering the significant evidence gap in this area, we sought to describe the coagulation disorders and thrombotic complications in patients with HFpEF and discuss the specific thromboembolic risk factors in patients with HFpEF, with the goal to tailor risk stratification to an individual patient.

Blood Coagulation Disorders in Heart Failure: From Basic Science to Clinical Perspectives.

Heart failure (HF) is a clinical syndrome that is divided into 3 subtypes based on the left ventricular ejection fraction. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and sinus rhythm, initial reports suggest that such strategy might be beneficial in a subset of patients at especially high thromboembolic risk. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation disorders in acute and chronic HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in special-case scenarios and to outline future research directions so as to establish the optimal patient-tailored strategies for antiplatelet and anticoagulant therapy in HF. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy. Further studies are urgently needed to shed light on the pathophysiological role of platelet activation in HF and to evaluate whether antiplatelet or antithrombotic therapy could be beneficial in patients with HF. LAY SUMMARY: Heart failure (HF) is a clinical syndrome divided into 3 subtypes on the basis of the left ventricular systolic function. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing the risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and no atrial arrhythmia, initial reports suggest that such a strategy might be beneficial in a subset of patients at especially high risk of thrombotic complications. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation problems in stable and unstable patients with HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in specific patient groups and to outline future research directions to establish the optimal strategies for antiplatelet and anticoagulant therapy in HF, tailored to the needs of an individual patient. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy.

Antithrombotic treatment switching in elderly patients with atrial fibrillation and the risk of thromboembolism, bleeding, and cardiac death.

Background: Risks of antithrombotic switching is not investigated in elderly atrial fibrillation patients. Objectives: To investigate the effectiveness and safety of antithrombotic treatment and switching of antithrombotic treatment in elderly patients (aged 75 years or older) with atrial fibrillation (AF). Methods: We conducted a cohort study of 2943 patients with AF (Carrebean-elderly), hospitalized during 2010-2017. Cox models were used to estimate the association of antithrombotic treatment (warfarin, direct oral anticoagulants [DOAC] and non-guideline-recommended therapy [NG], i.e., aspirin and low-molecular-weight heparin) at discharge and antithrombotic treatment switching during follow-up with the risk of a composite and single end points of thromboembolism, bleeding, and cardiac death. Crude and adjusted risk estimates were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). All-cause death was evaluated, with competing risk regression and estimates expressed as subhazard ratios and 95% CIs. Results: We observed an increased risk for the composite end point associated with NG as compared to warfarin at discharge (HR, 1.18; 95% CI, 1.01-1.38) with congruent competing risk regression results, while no significant risk difference was seen for DOACs compared to warfarin (HR, 1.12; 95% CI, 0.92-1.36). Switching from NG to warfarin/DOAC and from warfarin to DOAC occurred in 30.4% and 33.1% of respective antithrombotic treatment groups at discharge and was associated with a decreased risk for the composite end point with an adjusted HR of 0.45 (95% CI, 0.32-0.63) and a HR of 0.50 (95% CI, 0.38-0.65), respectively. Conclusions: Antithrombotic treatment switching is common in the elderly AF population. Importantly, switching to guideline-recommended treatment has a favorable impact on both effectiveness and safety.

Is the association of QTc with atrial fibrillation and stroke in cohort studies a matter of time?

OBJECTIVES: To investigate the association of the heart rate-corrected QT interval (QTc) with the risk of atrial fibrillation (AF) and ischaemic stroke. METHODS: We estimated the risk of AF and ischaemic stroke associated with QTc duration (ms) by Cox regression in study participants from the cohort of 60-year-old men and women from Stockholm (60YO) (n=4232). Univariate and multivariate adjusted risk estimates were expressed as HR and 95% CI. Main results were validated in elderly patients with AF, included in the Carebbean-e study, where an ECG in sinus rhythm (SR) (ECG-SR) recorded before the ECG diagnostic for (ECG-AF) was available (n=803). We estimated the correlation between the time interval (years) between the ECG-SR and ECG-AF with the QTc duration, by the Spearman correlation coefficient (rho). RESULTS: In the 60YO, the highest QTc duration quartile (>427 ms) associated with the AF risk (n=435) with a multivariable adjusted HR of 1.68 and 95% CI (1.26 to 2.24). No association was observed with ischaemic stroke. In the Carebbean-e study, no significant association was observed between the QTc duration measured on the ECG-SR and risk of ischaemic stroke during follow-up. QTc duration showed an inverse correlation (rho: -0.26, p<0.0001) with the time interval intercurred between ECG-SR and ECG-AF. CONCLUSIONS: The association of QTc duration with AF risk might depend on the time interval between the QTc measurement and the clinical diagnosis of AF. No association was observed between QTc duration and ischaemic stroke.

Coagulopathy and sepsis: Pathophysiology, clinical manifestations and treatment.

Sepsis is a complex syndrome with a high incidence, increasing by 8.7% annually over the last 20 years. Coagulopathy is a leading factor associated with mortality in patients with sepsis and range from slight thrombocytopenia to fatal disorders, such as disseminated intravascular coagulation (DIC). Platelet reactivity increases during sepsis but prospective trials of antiplatelet therapy during sepsis have been disappointing. Thrombocytopenia is a known predictor of worse prognosis during sepsis. The mechanisms underlying thrombocytopenia in sepsis have yet to be fully understood but likely involves decreased platelet production, platelet sequestration and increased consumption. DIC is an acquired thrombohemorrhagic syndrome, resulting in intravascular fibrin formation, microangiopathic thrombosis, and subsequent depletion of coagulation factors and platelets. DIC can be resolved with treatment of the underlying disorder, which is considered the cornerstone in the management of this syndrome. This review presents the current knowledge on the pathophysiology, diagnosis, and treatment of sepsis-associated coagulopathies.

Clinical characteristics and antithrombotic prescription in elderly hospitalized atrial fibrillation patients: A cross-sectional analysis of a Swedish single-center clinical cohort.

BACKGROUND: Antithrombotic treatment represents a dilemma in elderly patients with atrial fibrillation since both risk of thromboembolism and bleeding are age-dependent complications. A paradigm shift occurred over the past 10 years when aspirin was overcome by warfarin and further by the direct oral anticoagulants. Here we present a clinical practice-based analysis of a cohort of elderly inpatient atrial fibrillation patients and investigate the influence of clinical factors in the choice of antithrombotic strategy. METHODS: Study participants (n = 2943) are consecutive patients aged 75-104 years discharged from a Swedish university hospital with atrial fibrillation or atrial flutter as main diagnosis between November 1st 2010 and December 31st 2017. Cardiovascular risk factors, comorbidities and antithrombotic treatment at discharge were manually extracted from medical charts. A logistic regression analysis was performed to estimate predictors of the probability to receive direct oral anticoagulants (DOACs) compared to warfarin. RESULTS: Patients aged ≥90 y (n = 446, women 73%) showed the highest prevalence of cardiovascular comorbidities and the highest bleeding and thromboembolic risk. DOACs became more commonly prescribed than warfarin in 2016/2017 across all ages. However, the probability to receive DOAC as compared to warfarin was lower in the presence of high bleeding risk (OR 0,55; 95% CI 0,40-0,77; p = 0,00) and high thromboembolic risk (OR 0,74; 95% CI 0,59-0,94; p = 0,01). CONCLUSION: Elderly atrial fibrillation patients represent a heterogenous group where the oldest (≥90 years) show both a very high thromboembolic and bleeding risk profile. In the presence of high thromboembolic and bleeding risk, warfarin was still preferred over DOAC.