Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry.

BACKGROUND: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients. METHODS: Using data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype. RESULTS: Our study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course. CONCLUSIONS: Lymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.

Arrhythmogenic Ventricular Cardiomyopathy: Challenges With Complex Genetics and Variable Phenotypes.

After a 20-year-old woman suddenly died, autopsy showed characteristic findings of biventricular arrhythmogenic cardiomyopathy. Screening of her family members revealed the same desmoplakin gene mutation and imaging abnormalities predominantly involving the left ventricle. We describe the variable phenotypic expression in a family that shares a common gene variant. (Level of Difficulty: Advanced.).

A Meta-Analysis Comparing Aspirin Alone Versus Dual Antiplatelet Therapy for the Prevention of Venous Graft Failure Following Coronary Artery Bypass Surgery.

BACKGROUND: Aspirin (ASA) monotherapy is the current standard of care after coronary artery bypass grafting (CABG) to prevent saphenous vein graft (SVG) failure. Several small, randomized clinical trials (RCTs) have suggested that dual antiplatelet therapy (DAPT) may be more effective at preventing SVG failure than ASA alone; however, it is unclear whether some P2Y12 inhibitors are more effective than others for the prevention of SVG failure. METHODS: Scientific databases and websites were searched to find RCTs. Both traditional pairwise meta-analysis using random-effect model and network meta-analysis using mixed-treatment comparison models were performed to compare the efficacy of various anti-platelet strategies for the prevention of SVG failure. RESULTS: Nine RCTs, which included a total of 1677 patients, were analyzed. Compared to ASA alone, DAPT decreased the risk of graft failure by 37% (RR: 0.63, 95% CI: 0.47-0.86; p = 0.003). In the moderator analysis, the decreased risk of graft failure with DAPT was not significantly different in the ASA + clopidogrel group than in the ASA + ticagrelor group (P-interaction = 0.17). The results of the network meta-analysis were consistent with those from pairwise analyses. The risk of major bleeding was not statistically significantly different between DAPT and ASA alone (RR: 1.35, 95% CI: 0.62-2.94; p = 0.45). CONCLUSION: In post-CABG patients, DAPT seems to be more effective at preventing graft failure than ASA alone. This strategy does not seem to significantly increase major bleeding risk. Clopidogrel- and ticagrelor-based DAPT seem to be equally effective for this indication.

From WOEST to AUGUSTUS: a review of safety and efficacy of triple versus dual antithrombotic regimens in patients with atrial fibrillation requiring percutaneous coronary intervention for acute coronary syndrome.

For patients with atrial fibrillation with concomitant acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI), the increased risk of bleeding associated with the use triple therapy is well established. However, there is question whether it is a necessary risk for patients to prevent stroke and stent thrombosis. The purpose of this article is to highlight the findings of prior studies evaluating the comparative safety and efficacy of dual and triple antithrombotic regimens in the subgroup of atrial fibrillation patients requiring PCI for ACS. Trials that evaluated dual versus triple antithrombotic therapy demonstrated post-PCI treatment with a P2Y12 inhibitor alone was safer than aspirin plus a P2Y12 inhibitor in patients also taking an anticoagulant for atrial fibrillation. Data regarding ischemic outcomes have not suggested harm with the omission of aspirin, but these studies have not been powered to assess efficacy outcomes, especially in ACS patients. These studies also demonstrate a significant reduction in bleeding events when aspirin is excluded from the post-PCI regimen in the ACS subgroup of atrial fibrillation patients. Further studies, with added focus on the ACS subgroup, are needed to potentially confirm that dual therapy may be as efficacious as triple therapy in ACS patients with atrial fibrillation.

Post-operative atrial fibrillation: should we anticoagulate?

The prevalence of atrial fibrillation (AF) is estimated to be 12 million by the year 2030. A subset of those patients fall into the category of post-operative atrial fibrillation (POAF) and either develop POAF after cardiac procedures [coronary artery bypass graft (CABG) and valvular procedures] or non-cardiac procedures. With the rise in surgical procedures, POAF represents a significant economic burden. POAF usually converts to sinus rhythm on its own, prompting questions about whether there is a need to treat it and if there is a need for anticoagulation. This review discusses risk factors, pathophysiology, complications of POAF, and mechanisms of risk stratifying patients to determine when to anticoagulate.

Targeting ticagrelor: a novel therapy for emergency reversal.

Newer P2Y12 inhibitors are prescribed in place of clopidogrel for patients with acute coronary syndrome (ACS) and are associated with significant bleeding risks. Currently, limited options exist for the management of life-threatening bleeding or acute reversal for patients on P2Y12 inhibitor therapy, specifically ticagrelor. Various interventions, including platelet transfusion and desmopressin, have been studied for ticagrelor reversal demonstrating limited success. PB2452 is a novel monoclonal antibody which binds to both ticagrelor and its active metabolite resulting in a rapid return of platelet aggregation. PB2452 has been studied in animal models and, most recently, in a Phase I trial in healthy volunteers. In animal models, PB2452 displayed rapid reversal of ticagrelor and its metabolites and return to near normal levels of platelet aggregation within 60 min. In healthy human volunteers, cohorts that received higher dose bolus and infusions of PB2452 over 12-16 h resulted in maximal and sustained reversal of ticagrelor inhibition of platelet aggregation. While it is currently not US Food and Drug Administration approved, future Phase 2 and 3 studies are currently underway that may lead to new directions for patients on ticagrelor therapy who require urgent reversal.

Current status of oral anticoagulant reversal strategies: a review.

Utilization of direct oral anticoagulants (DOAC) have steadily increased since their approval and are now recommended over warfarin for both stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism (VTE). With increased DOAC use, the number of major bleeding events requiring medical intervention will continue to rise. Until 2015, warfarin maintained an advantage as the only oral anticoagulant with a specific reversal agent. Since then, idarucizumab has been approved for dabigatran reversal and recently, andexanet alfa was granted approval for the reversal of apixaban or rivaroxaban in patients with life-threatening or uncontrolled bleeding events. Due to the manufacturing practices required to yield these reversal therapies, they are available at high cost to hospital systems and as a result, have been met with resistance. Data exists describing both prothrombin complex concentrates (PCC) and andexanet alfa for DOAC reversal, however, without head-to-head comparison. Until future studies are available, current literature must be critically evaluated to aid in the clinical decision-making process of how to treat patients with life-threatening DOAC-related bleeding.

Is there an optimal "door to cath time" in the treatment of acute pulmonary embolism with catheter-directed thrombolysis?

Ultrasound assisted catheter-directed thrombolysis (UACT) is a relatively novel approach to treating acute pulmonary embolism (PE). It is an alternative to systemic thrombolysis with good success rates and low reported in-hospital mortality, and low rates of procedure-related major and minor bleeding. Since UACT received FDA approval for the treatment of PE in 2014, there is paucity of data regarding the optimal timing of initiation of the procedure after the initial diagnosis is made. We reviewed the available literature regarding UACT for acute PE and found six studies that included time to procedure. Based on our review, patients may benefit from early (<24-48 h after presentation) rather than delayed (>48 h) initiation. Early initiation of therapy has shown to improve pulmonary arterial pressures, right ventricular (RV) to left ventricular (LV) ratios, with low rates of bleeding and low post procedural and in hospital mortality. However, further studies are required to confirm these findings and establish the appropriate timeline for initiation of UACT.

Accuracy of non-invasive and minimally invasive hemodynamic monitoring: where do we stand?

One of the most important variables in assessing hemodynamic status in the intensive care unit (ICU) is the cardiac function and blood pressure. Invasive methods such as pulmonary artery catheter and arterial line allow monitoring of blood pressure and cardiac function accurately and reliably. However, their use is not without drawbacks, especially when the invasive nature of these procedures and complications associated with them are considered. There are several newer methods of noninvasive and minimally invasive hemodynamic monitoring available. In this manuscript, we will review these different methods of minimally invasive and non-invasive hemodynamic monitoring and will discuss their advantages, drawbacks and limitations.

From Tick Bite to Heart Failure: Ehrlichial Myocarditis.

Cardiac involvement in myocarditis induced by Human Monocytic Ehrlichiosis infection is an incredibly uncommon complication with sparsely available literature. Also, this case highlights the importance of early recognition as a first step in management.

Une atteinte cardiaque secondaire à une myocardite induite par une ehrlichiose monocytaire humaine constitue une complication extrêmement rare et très peu documentée. Le cas présenté fait ressortir l'importance d'une reconnaissance rapide du problème comme première étape de la prise en charge.