Rationale, design, and methods for a pivotal randomized clinical trial for the assessment of a cardiac support device in patients with New York health association class III-IV heart failure

BACKGROUND: Heart failure remains a progressive disease with incremental morbidity and mortality despite optimal medical therapy. A growing body of evidence suggests that progressive left ventricular (LV) remodeling is directly related to a deterioration in LV performance and untoward clinical outcomes for heart failure patients. Preclinical and early phase I clinical studies with the CorCap Cardiac Support Device (CSD), a passive cardiac support device that prevents cardiac remodeling, have shown that it is safe and is associated with improvements in LV structure and function, as well as patient symptomatology. METHODS AND RESULTS: The Acorn Pivotal Trial is a pivotal prospective, randomized, evaluation of the CorCap CSD in patients with New York Heart Association class III-IV heart failure. Patients will be enrolled into one of two different strata. Patients who require a mitral valve repair/replacement (MVR) will fall into the "MVR stratum" and will be randomized to either treatment (MVR surgery plus the CSD) or control (MVR surgery alone). Patients who do not have a clinical indication for MVR surgery will fall into the "no-MVR stratum" and will also be randomized to either treatment (CSD implant plus optimal medical therapy) or control (optimal medical therapy alone). A total of 300 patients (150 treatment and 150 control) will be enrolled. The primary endpoint of the trial is the change in clinical status from baseline to the end of the efficacy phase (1 year), as determined by a clinical composite score. Patients will be classified as improved, worsened, or unchanged based upon patient vital status, the occurrence of a major cardiac procedure indicative of heart failure progression, and a change in the assessment of New York Heart Association functional class. CONCLUSIONS: The Acorn Pivotal Trial will formally test the hypothesis that preventing LV remodeling using a passive cardiac support device will favorably impact the untoward natural history of heart failure and thus represents an important departure from all previous medical and device studies that have been reported to date.     

A five-year clinical audit of concussive injuries in South African collegiate male rugby players—a South African experience

Sport Sciences for Health - Sports-related concussion (SRC) is a common injury mostly in contact sports. Specifically, it is a public health concern for collegiate rugby athletes because at least...     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.     

The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure

OBJECTIVES: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF). BACKGROUND: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity. METHODS: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses. RESULTS: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%. CONCLUSION: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables.