Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR. Future trials should examine the mechanisms responsible for these improvements, and if such improvements translate into improved clinical outcomes. (Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices:Rehab VAD Trial [RehabVAD]; NCT01584895).

Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.

Background Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction (HFrEF) is well established, there is limited data on the value of CPX variables in patients with HF and preserved EF (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. Methods This was a retrospective analysis of patients with HFpEF (EF ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included; peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production (VE/VCO2) slope and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant (CTx). Results We identified 173 HFpEF patients (45% women; 58% non-white; age = 54±14 y) with complete CPX data. During a median follow-up of 5.2 y there were 42 deaths and 5 CTx. The 1, 3, and 5 y cumulative event-free survival was 96%, 90%, and 82% respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and beta-blockade therapy, ppMVO2 was the strongest predictor of the endpoint (Wald χ2 = 15.0, HR per 10% = p < 0.001), followed by peak VO2 (Wald χ2 = 11.8, p = 0.001). VE/VCO2 slope (Wald χ2 = 0.4, p = 0.54) and EOV (Wald χ2 = 0.15, p = 0.70) had no significant association to the composite outcome. Conclusion These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low and high risk patients.

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Cardiac transplantation remains the best treatment in advanced heart failure patients with a high risk of death. However, an inadequate supply of donor hearts decreases the likelihood of transplantation for many patients. Ventricular assist devices (VAD) are being increasingly used as a bridge to transplant in patients who may not survive long enough to receive a heart. This expansion in VAD use has been associated with increasing rates of allosensitization in cardiac transplant candidates. Anti-HLA antibodies can be detected prior to transplantation using different techniques. Complement-dependent lymphocytotoxicity assays are widely used to measure the panel reactive antibody (PRA), and for crossmatch purposes. Newer assays using solid phase flow techniques feature improved specificity and offer detailed information concerning antibody specificities, which may lead to improvements in donor-recipient matching. Allosensitization prolongs the wait time for transplantation and increases the risk of post-transplant complications and death; therefore, decreasing anti-HLA antibodies in sensitized transplant candidates is of vital importance. Plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab have been used to decrease the PRA prior to transplantation with varying degrees of success. The most significant post-transplant complications seen in allosensitized recipients are antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). AMR often manifests with severe allograft dysfunction and hemodynamic compromise. The underlying pathophysiology is not fully understood, but appears to involve complement-mediated activation of endothelial cells resulting in ischemic injury. The treatment of AMR in cardiac recipients is largely empirical, and includes high-dose corticosteroids, plasmapheresis, IVIG and rituximab. Cardiac allograft vasculopathy (CAV) is characterized by diffuse concentric stenosis of allograft coronary arteries due to intimal expansion. Its pathophysiology is unclear, but may involve chronic complement-mediated endothelial injury. Sirolimus and everolimus can delay the progression of CAV. In some non-sensitized cardiac transplant recipients, the de novo formation of anti-HLA antibodies after transplantation may increase the likelihood of adverse clinical outcomes. Serial post-transplant PRAs may be advisable in patients at high risk of de novo allosensitization.