Objective: To determine whether heritable thrombophilia and hypofibrinolysis were risk factors for retinal vein occlusion. Design: Measures of thrombophilia (increased likelihood of thrombus formation) included anticardiolipin antibodies (IgG and IgM), the lupus anticoagulant (including dilute Russell viper venom clotting time), antigenic proteins C and S, and homocysteine. Polymerase chain reaction assays were performed for 3 thrombophilic gene mutations (factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene). Measures of hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein Lp(a), plasminogen activator inhibitor activity, and polymerase chain reaction analysis of the hypofibrinolytic 4G/5G polymorphism of the PAI1 gene. These coagulation measures were performed in 17 patients with retinal vein occlusions with comparison with serologic coagulation measures and polymerase chain reaction assays in 40 and 234 healthy normal volunteers as controls, respectively. Results: Of 14 patients with retinal vein occlusion with measures of dilute Russell viper venom clotting time, a thrombophilic antiphospholipid antibody, 6 (43%) had abnormal results (Ͼ38.8 seconds) compared with 1 (3%) of 30 controls (P = .002). Of 17 patients with vein occlusion, 3 (18%) were heterozygous for the thrombophilic factor V Leiden G1691A mutation compared with 7 (3%) of 233 controls (P = .02). Of 17 patients with vein occlusion, 2 (12%) had normal alleles (5G/5G) for the plasminogen activator inhibitor gene promoter; the other 15 (88%) were heterozygous or homozygous for the 4G polymorphism, which is associated with hypofibrinolysis. Of 234 controls, 85 (36.3%) had the 5G/5G allele; 149 (63.7%) were heterozygous or homozygous for the 4G polymorphism (P = .03). Patients with vein occlusion were more likely to have high levels of the major determinant of hypofibrinolysis, plasminogen activator inhibitor activity. These levels were high (Ͼ22 U/L) in 6 (38%) of 16 patients with vein occlusion compared with 1 (2%) of 40 controls (2 = 12.8; P = .001). Patients with vein occlusion were more likely (8/16 [50%]) to have high levels of hypofibrinolytic Lp(a) (Ͼ35 mg/dL) than controls (5/40 [13%]; 2 = 9; P = .003). The median Lp(a) level in patients with vein occlusion who had the 4G/4G genotype was 62 mg/dL compared with 5.3 mg/dL in controls with the 4G/4G genotype (P = .05). Conclusion: Thrombophilia and hypofibrinolysis are possible causes of retinal vein occlusion.

Tumor necrosis factor a (TNF-alpha) is a proinflammatory cytokine that is produced by activated macrophages. It has been shown to stimulate the release of endothelial cytokines and NO, increase vascular permeability, decrease contractility, and induce a prothrombotic state. The most studied TNF-a gene mutation in heart disease is a gamma to alpha substitution, which occurs when 308 nucleotides move upstream from the transcription initiation site in the TNF promoter and has been associated with elevated levels of TNF-alpha. The TNF1 allele (wild type) contains gamma at this site, while the TNF2 allele has an alpha substitution at the site. The TNF2 allele is a more powerful transcriptional activator, therefore leading to higher TNF-alpha levels. Most of the studies to date have failed to conclusively show any link between the polymorphism and heart disease, both coronary artery disease and cardiomyopathy/heart failure.

Our understanding of the pathophysiology of chronic heart failure is rapidly expanding. recent investigations suggest a role for various proinflammatory and vasoconstrictive cytokines in the development and progression of the disease. In particular, tumor necrosis factor-alpha, interlukin-6, and endothelin have all been implicated in heart failure desease progression. These cytokines appear to be activated in response to a remodeling, induction of programmed cell death, neurohormonal activation, and hemodynamics, these agents cause a variety of deleterious effects in the setting of ventricular dysfunction. Investigational inhibitors and antagonists of these substances show promise for the future treatment of heart failure.

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The purpose of this systematic literature review is to examine the current state of the science on caregiver care for those caring for end stage heart failure patients that have been implanted with a LVAD utilizing Uncertainty in Illness Theory (UIT). Methods: Five major databases were searched to identify relevant studies published in English between 1999 and September 2015. Each study was abstracted and confirmed by two authors and was identified and theoretically categorized. Analyses across studies were also performed. Results: Twenty-two eligible papers were included in this review. The majority of included studies were qualitative in nature with only four attempting to quantify caregiver experiences. Caregiver experiences were organized into factors leading to uncertainty, appraisal of uncertainty, coping processes and longterm outcomes. Anxiety, depression, post-traumatic stress syndrome, distress, fears, and sexual concerns are negative psychosocial factors experienced from uncertainty, while caregivers also experience hope and optimism. Adaptation occurs when the caregivers have accepted their role a caregiver. Conclusions: This is the first comprehensive theory based review in LVAD caregiver literature. Our analysis provides evidence for a rapidly developing science that is based largely on observational and qualitative research. However, few studies examine the caregiver and LVAD patient as a dyad. Longitudinal and quantitative research studies are needed with sufficiently large sample sizes to examine the variables in caregiving experience and how it impacts patient outcomes to inform future interventions.