Prosthetic Mitral Valve Thrombosis in Pregnancy: From Thrombolysis to Anticoagulation

INTRODUCTION: Pregnant women with mechanical prosthetic heart valves are at increased risk for valve thrombosis. Management decisions for this life-threatening complication are complex. Open-heart surgery has a very high risk of maternal mortality and fetal loss. Bleeding and embolic risks associated with thrombolytic agents, the limited efficacy of thrombolysis in certain subgroups, and a lack of experience in the setting of pregnancy raise important concerns. CASE REPORT: We report a case of mitral prosthetic valve thrombosis in early pregnancy, which was successfully treated with streptokinase. Ten years later, the same patient had an uneventful pregnancy, throughout which acenocoumarol was maintained. CONCLUSION: With this case we review the prevention (with oral anticoagulant therapy) and treatment of prosthetic valve thrombosis during pregnancy, which is important for both obstetrician and cardiologist.

Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Intraocular Pressure in Eyes Receiving Intravitreal Antivascular Endothelial Growth Factor Injections

PURPOSE: The aim of the this study was to determine the effect of intravitreal antivascular endothelial growth factor injections on intraocular pressure (IOP) and identify possible risk factors for the development of increased IOP. MATERIALS AND METHODS: This prospective study included a total of 106 eyes receiving intravitreal injection of bevacizumab as treatment for macular edema or active choroidal neovascularization. IOP was measured by Goldmann applanation tonometry immediately before the intravitreal injection and 5 min, 1 h and 15 days after the procedure. The records of the study patients were reviewed for age, gender, history of glaucoma, diabetes mellitus, phakic status, systemic and topical medication and number of previous injections. Subconjunctival reflux was registered. IOP elevation was defined as IOP ≥21 mm Hg and/or a change from baseline of ≥5 mm Hg recorded at least on two or more measurements on the same visit. RESULTS: Mean preoperative IOP was 15.31 ± 3.90 mm Hg and postoperative IOP values were 27.27 ± 11.87 mm Hg (after 5 min), 17.59 ± 6.24 mm Hg (after 1 h) and 16.86 ± 3.62 mm Hg (after 15 days). The IOP variation was statistically significant between pre- and postoperative measurements (p < 0.05). Subconjunctival reflux was recorded in 11.3%, and in this subgroup the IOP at 5 min and at 1 h was lower than preoperative IOP (p < 0.05). CONCLUSIONS: More than one third of the eyes achieved IOPs >30 mm Hg 5 min after injection. Subconjunctival reflux contributed to a lower mean postoperative IOP (p < 0.05). Considerations for the management include prophylactic IOP lowering with medical therapy and/or preinjection ocular decompression for patients with a history of glaucoma or ocular hypertension and switching to an as-needed injection protocol in patients suffering a marked IOP rise in previous injections. © 2015 S. Karger AG, Basel.

Health-Related Quality of Life Impact of a Triple Combination of Olmesartan Medoxomil, Amlodipine Besylate and Hydrochlorotiazide in Subjects with Hypertension

BACKGROUND: A post-hoc analysis was performed on the data from a 54 weeks phase III study (ClinicalTrials.gov identifier: NCT00923091) to measure changes in the health-related quality of life (HRQoL) of 2,690 patients aged ≥18 with moderate-to-severe hypertension who received one of six doses of olmesartan/amlodipine/hydrochlorothiazide (OLM/AML/HCTZ), using the MINICHAL and EQ-5D instruments. METHODS: Descriptive statistics were used to assess blood pressure and HRQoL scores over the study period. Analysis of covariance (ANCOVA) was used to identify those factors that could possibly have influenced HRQoL. Linear regression was used to assess the relationship between changes in blood pressure and HRQoL scores. RESULTS: Patients' baseline MINICHAL mood and somatic domains scores were 5.5 and 2.6. Over the study period HRQoL improved as both MINICHAL scores decreased by 31-33%. Patients' baseline EQ-5D index and VAS scores were 0.9 and 73.4 respectively, increasing by 6% and 12% over the study period. Patients' QALY gain over the 54 weeks study period was estimated to be 0.029 QALYs. The ANCOVA showed that changes in patients' HRQoL was likely to have been influenced by patients' achievement of blood pressure control, the amount of concomitant medication and patients' last used dosage strength of antihypertensive. Linear regression showed that blood pressure improvement may have been associated with improved HRQoL. CONCLUSIONS: This study showed that OLM/AML/HCTZ reduced blood pressure and significantly increased blood pressure control whilst improving patients' HRQoL. Achieving blood pressure control, amount of concomitant medication and dosage strength of antihypertensive impacted on patients' HRQoL.

Atorvastatin versus Bezafibrate in Mixed Hyperlipidaemia : Randomised Clinical Trial of Efficacy and Safety (the ATOMIX Study)

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels <200 mg/dL were achieved in 52% and 60% of patients, respectively. In patients with normal baseline HDL-C, bezafibrate was superior to atorvastatin for raising HDL-C, while in those with baseline HDL-C <35 mg/dL, the two drugs raised HDL-C to a similar extent after adjustment for baseline values. Both drugs were well tolerated. CONCLUSION: The results show that atorvastatin has an overall better efficacy than bezafibrate in concomitantly reaching LDL-C and triglyceride target levels in combined hyperlipidaemia, thus supporting its use as monotherapy in patients with this lipid phenotype.

Intramural Hematoma of the Esophagus After Thrombolysis for Ischemic Stroke

Intramural dissecting hematoma is an unusual esophageal condition with a threatening presentation but excellent prognosis when managed conservatively.We report the case of an 88-year-old woman who developed an intramural hematoma of the esophagus after intravenous thrombolysis for an acute ischemic stroke. Before thrombolysis, nasogastric intubation was attempted unsuccessfully. She was kept on nil by mouth, intravenous hydration, proton pump inhibitor, antiemetics,and an antibiotic initiated 2 days before for periodontal disease. The esophageal hematoma regressed, and she resumed oral diet asymptomatically.To our knowledge, this is the first report of this type of lesion after thrombolysis for an ischemic stroke. A brief discussion and literature review are presented.

Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment

Background: Rett disorder (RD) is a progressive neurodevelopmental entity caused by mutations in the MECP2 gene. It has been postulated that there are alterations in the levels of certain neurotransmitters and folate in the pathogenesis of this disease. Here we re-evaluated this hypothesis. Patients and Methods: We evaluated CSF folate, biogenic amines and pterines in 25 RD patients. Treatment with oral folinic acid was started in those cases with low folate. Patients were clinically evaluated and videotaped up to 6 months after therapy. Results: CSF folate was below the reference values in 32% of the patients. Six months after treatment no clinical improvement was observed. Three of the four patients with the R294X mutation had increased levels of a dopamine metabolite associated to a particular phenotype. Three patients had low levels of a serotonin metabolite. Two of them were treated with fluoxetine and one showed clinical improvement. No association was observed between CSF folate and these metabolites, after adjusting for the patients age and neopterin levels. Conclusion: Our results support that folinic acid supplementation has no significant effects on the course of the disease. We report discrete and novel neurotransmitter abnormalities that may contribute to the pathogenesis of RD highlighting the need for further studies on CSF neurotransmitters in clinically and genetically well characterized patients.

Ophthalmoplegic Migraine and Infundibular Dilatation of a Cerebral Artery

Ophthalmoplegic migraine (OM) is a childhood disorder of uncertain etiology manifesting recurrent unilateral headache associated with a transitory oculomotor (usually IIIrd nerve) palsy. Recent publications emphasize the finding on MRI of contrast enhancement in the IIIrd nerve suggesting that OM may be a recurrent inflammatory neuropathy. We report the case of a 7-year-old boy with typical symptoms of this disorder. Angio MR and Angio CT revealed the presence of an infundibular dilatation of a perforating branch of the posterior cerebral artery adjacent to the symptomatic IIIrd nerve. We speculate that this and perhaps other cases of OM may have a different pathophysiology related to compression of the IIIrd nerve by an adjacent vascular structure that could activate the trigeminovascular system and produce migrainous pain.

Aortic and Tricuspid Endocarditis in Hemodialysis Patient with Systemic and Pulmonary Embolism

This is a case report of a 43-year-old Caucasian male with end-stage renal disease being treated with hemodialysis and infective endocarditis in the aortic and tricuspid valves. The clinical presentation was dominated by neurologic impairment with cerebral embolism and hemorrhagic components. A thoracoabdominal computerized tomography scan revealed septic pulmonary embolus. The patient underwent empirical antibiotherapy with ceftriaxone, gentamicin and vancomycin, and the therapy was changed to flucloxacilin and gentamicin after the isolation of S. aureus in blood cultures. The multidisciplinary team determined that the patient should undergo valve replacement after the stabilization of the intracranial hemorrhage; however, on the 8th day of hospitalization, the patient entered cardiac arrest due to a massive septic pulmonary embolism and died. Despite the risk of aggravation of the hemorrhagic cerebral lesion, early surgical intervention should be considered in high-risk patients.

Cost-Effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation in Portugal

INTRODUCTION AND OBJECTIVES:Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. METHODS: A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). RESULTS:Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. CONCLUSIONS:Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.