Anatomic Approach to Transseptal Puncture for Structural Heart Interventions

The use of transseptal puncture continues to rise given the increase in left atrial cardiac interventions. The authors review an anatomic approach to transseptal puncture incorporating multimodality imaging both pre- and intraprocedurally with stepwise escalation algorithms to ensure safe and efficacious large-bore transseptal puncture.     

"Panning" for lymphocytes: a method for cell selection.

We have developed a simple method for the fractionation of T and B lymphocytes. Plastic dishes coated with antibodies specific for mouse Ig selectively bind splenic B lymphocytes. The adherent cells are easily removed by gentle pipetting; both adherent and nonadherent populations retain immunologic function. In a typical experiment, when 3 X 10(7) splenic lymphocytes were added to a 100 X 15 mm plastic dish coated with microgram quantities of anti-Ig, 98 % of the nonadherent cells were Ig negative and 97% of the adherent cells were Ig positive. The method is sufficiently sensitive to allow detection and separation of cell types comprising as little as 2% of the total population and can be modified to allow the selection of cells by a double-antibody procedure. We believe that the plastic dish method will be generally useful for fractionating cells on the basis of their cell surface antigens.     

Stent Repair for Complex Coarctation of Aorta

ObjectivesThis study sought to determine whether several anatomic or evolving characteristics of the coarctation may create challenging conditions for treatment.BackgroundStent repair of coarctation of aorta is an alternative to surgical correction.MethodsWe analyzed our 21-year experience in the percutaneous treatment of complex coarctation of aorta. Adverse conditions for treatment were as follow: 1) complete interruption of the aortic arch (n = 11); 2) associated aneurysm (n = 18); 3) complex stenosis (n = 30); and 4) the need for re-expansion and/or restenting (n = 21). Twenty patients (33%) belonged to more than 1 group. Ten interruptions were type A and 1 was type B. The mean length of the interrupted aorta was 9 ± 11 mm. The associated aneurysms were native in 8 patients and after previous intervention in 10 patients. Aneurysm shapes were fusiform in 8 patients and saccular in 10. The following characteristics defined complex stenosis as long diffuse stenosis, very tortuous coarctation, or stenosis involving a main branch or an unusual location. Patients previously stented at an early age, required re-expansion and/or restenting after reaching 16 ± 5 years of age.ResultsTwo patients had died by 1-month follow-up. The remaining 58 patients did well and were followed-up for a mean period of 10 ± 6 years. Late adverse events occurred in 3 patients (5%). All remaining patients are symptom-free, with normal baseline blood pressure. Imaging techniques revealed good patency at follow-up without associated aneurysm or restenosis. The actuarial survival free probability of all complex patients at 15 years was 92%.ConclusionsStent repair of complex coarctation of aorta is feasible and safe. Initial results are maintained at later follow-up.     

Amyloid‐ß‐directed immunotherapy for Alzheimer's disease

Current treatment options for Alzheimer's disease (AD) are limited to medications that reduce dementia symptoms. Given the rapidly ageing populations in most areas of the world, new therapeutic interventions for AD are urgently needed. In recent years, a number of drug candidates targeting the amyloid‐ß (Aß) peptide have advanced into clinical trials; however, most have failed because of safety issues or lack of efficacy. The Aß peptide is central to the pathogenesis, and immunotherapy against Aß has attracted considerable interest. It offers the possibility to reach the target with highly specific drugs. Active immunization and passive immunization have been the most widely studied approaches to immunotherapy of AD. A favourable aspect of active immunization is the capacity for a small number of vaccinations to generate a prolonged antibody response. A potential disadvantage is the variability in the antibody response across patients. The potential advantages of passive immunotherapy include the reproducible delivery of a known amount of therapeutic antibodies to the patient and rapid clearance of those antibodies if side effects develop. A disadvantage is the requirement for repeated infusions of antibodies over time. After more than a decade of research, anti‐amyloid immunotherapy remains one of the most promising emerging strategies for developing disease‐modifying treatments for AD. In this review, we examine the presently ongoing Aß‐directed immunotherapies that have passed clinical development Phase IIa.     

Methodological Standardization for the Pre-Clinical Evaluation of Renal Sympathetic Denervation

Transcatheter ablation of renal autonomic nerves is a viable option for the treatment of resistant arterial hypertension; however, structured pre-clinical evaluation with standardization of analytical procedures remains a clear gap in this field. Here we discuss the topics relevant to the pre-clinical model for the evaluation of renal denervation (RDN) devices and report methodologies and criteria toward standardization of the safety and efficacy assessment, including histopathological evaluations of the renal artery, periarterial nerves, and associated periadventitial tissues. The pre-clinical swine renal artery model can be used effectively to assess both the safety and efficacy of RDN technologies. Assessment of the efficacy of RDN modalities primarily focuses on the determination of the depth of penetration of treatment-related injury (e.g., necrosis) of the periarterial tissues and its relationship (i.e., location and distance) and the effect on the associated renal nerves and the correlation thereof with proxy biomarkers including renal norepinephrine concentrations and nerve-specific immunohistochemical stains (e.g., tyrosine hydroxylase). The safety evaluation of RDN technologies involves assessing for adverse effects on tissues local to the site of treatment (i.e., on the arterial wall) as well as tissues at a distance (e.g., soft tissue, veins, arterial branches, skeletal muscle, adrenal gland, ureters). Increasing experience will help to create a standardized means of examining all arterial beds subject to ablative energy and in doing so enable us to proceed to optimize the development and assessment of these emerging technologies.     

Expert Recommendations on Cardiac Computed Tomography for Planning Transcatheter Left Atrial Appendage Occlusion

Transcatheter left atrial appendage occlusion is an increasingly used alternative to oral anticoagulation in selected patients with atrial fibrillation. Pre-procedural imaging is a prerequisite to a successful intervention, with transesophageal echocardiography as the current gold standard. However, cardiac computed tomography offers improved imaging with high-quality multiplanar and 3-dimensional reconstructed images. Nevertheless, the lack of a standardized imaging protocol has slowed the adoption of cardiac computed tomography into clinical practice. On the basis of current research and expert consensus, this paper provides a protocol for the preparation, acquisition, and interpretation of cardiac computed tomographic imaging in pre-procedural planning of left atrial appendage occlusion.     

Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review

Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure, but in contrast to other therapies, robust clinical trial evidence to guide the use of diuretics is sparse. A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for skillful use of diuretics in the management of heart failure in both the inpatient and outpatient settings. Diuretic resistance, defined as an inadequate quantity of natriuresis despite an adequate diuretic regimen, is a major clinical challenge that generally portends a poor prognosis. In this review, the authors discuss the fundamental mechanisms and physiological principles that underlie the use of diuretic therapy and the available data on the optimal use of diuretics.     

Treatment for life for severe haemophilia A– A cost‐utility model for prophylaxis vs. on‐demand treatment

Prophylaxis has been established as the treatment of choice in children with haemophilia and its continuation into the adult years has been shown to decrease morbidity throughout life. The cost of factor therapy has made the option questionable in cost‐effectiveness studies. The role of prophylaxis in pharmacokinetic dosage and tolerization against inhibitor formation were used to model the cost utility of prophylaxis vs. on‐demand (OD) therapy over a lifetime horizon in severe haemophilia A. The model was applied to a single provider national health system exemplified by the United Kingdom's National Health Service and a third party provider in the United States. The incremental cost‐effectiveness ratio (ICER) was estimated and compared to threshold values used by payer agencies to guide reimbursement decisions. A cost per quality‐adjusted life year (QALY) was also estimated for Sweden. Prophylaxis was dominant over OD treatment in the UK. The model resulted in an ICER – $68 000 – within the range of treatments reimbursed in the USA. In Sweden, a cost/QALY of SEK 1.1 million was also within the range of reimbursed treatments in that country. Dosage‐ and treatment‐induced inhibitor incidence were the most important variables in the model. Subject to continuing clinical evidence of the effectiveness of pharmacokinetic dosage and the role of prophylaxis in decreasing inhibitor incidence, treatment for life with prophylaxis is a cost‐effective therapy, using current criteria for the reimbursement of health care technologies in a number of countries.     

Point‐of‐care testing as a tool for screening for diabetes and pre‐diabetes

Aim To determine the utility of finger‐prick point‐of‐care testing (POCT) of blood glucose for the detection of dysglycaemia. Methods A fasting POCT and an oral glucose tolerance test (OGTT) with laboratory assays were performed as part of the baseline screening for 5309 participants enrolled in the Te Wai o Rona Diabetes Prevention Strategy. Participants were aged 46 ± 19 years with no self‐reported diabetes. Dysglycaemia, including diabetes, was defined using World Health Organization criteria. Agreement between the two fasting plasma glucose measurements and their screening properties (with sensitivity and specificity for cut points) were compared using receiver operator characteristic analysis. Results A total of 3225 participants had both capillary and venous fasting blood sampled within 30 min and then underwent OGTT. New diabetes was found in 161 participants (5.0%) and pre‐diabetes in 414 [impaired glucose tolerance 299 (9.3%), impaired fasting glucose 115 (3.6%)]. The mean difference in capillary and venous measures was 0.02 mmol/l (95% confidence interval ?0.04 to +0.01; limits of agreement –1.37 to 1.33 mmol/l). Capillary POCT was a poorer predictor of dysglycaemia and impaired glucose tolerance and new diabetes (area under curve 0.76 and 0.71) than venous laboratory analysis (area under curve 0.87 and 0.81 respectively). Optimal screening criteria were best at a venous glucose of 5.4 mmol/l; 77% sensitivity/specificity. Conclusions POCT significantly underestimated the true blood glucose at diagnostic levels for diabetes. POCT cannot be recommended as a means of screening for or diagnosing diabetes or pre‐diabetes.