Catheter Ablation of Tachyarrhythmias in Small Children

An estimated 80,000-100,000 radiofrequency ablation (RFA) procedures are performed in the United States each year.1 Approximately 1% of these are performed on pediatric patients at centers that contribute data to the Pediatric Radiofrequency Registry.2 Previous reports from this registry have demonstrated that RFA can safely and effectively be performed in pediatric patients.3,4 However, patients weighing less than 15 kg have been identified as being at greater risk for complications.3,4 Consequently, there has been great reluctance to perform RFA in small children such that children weighing less than 15 kg only represent approximately 6% of the pediatric RFA experience2 despite the fact that this age group carries the highest incidence of tachycardia, particularly supraventricular tachycardia (SVT).5 Factors other than the risk of complications contribute to the lower incidence of RFA in this group, including the natural history of the most common tachycardias (SVT), technical issues with RFA in small hearts, and the potential unknown long-term effects of RF applications in the maturing myocardium. Conversely, there are several reasons why ablation may be desirable in small children, including greater difficulties with medical management,6,7,8 the higher risk for hemodynamic compromise during tachycardia in infants with congenital heart disease (CHD), and the inability of these small children to effectively communicate their symptoms thereby making it more likely that their symptoms may go unnoticed until the children become more seriously ill. Before ultimately deciding that catheter ablation is indicated in small children, one must consider which tachycardias are likely to be ablated, the clinical presentation of these tachycardias, alternatives to ablation, the relative potential for success or complications, and modifications of the procedure that might reduce the risk of ablation in this group

Positron emission tomography agent 2-deoxy-2-[(18)F]fluoro-D-glucose has a therapeutic potential in breast cancer

BACKGROUND: Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. METHODS: Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5–1 cm in diameter were imaged with (18)F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of (18)F-FDG administration was determined in healthy mice. PyMT mice with small (0.15–0.17 cm) and large (more than 1 cm) tumors were treated with 2–4 mCi of (18)F-FDG, and control C3H/B6 mice with 3 mCi of (18)F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The (18)F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human (18)F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered by (18)F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of (18)F-FDG makes it suitable for therapy of this malignancy

Electrophysiologic Studies and Radiofrequency Catheter Ablation of Ectopic Atrial Tachycardia in Children

Ectopic atrial tachycardia (EAT) often resists medical therapy, making radiofrequency catheter ablation (RFCA) the preferred treatment. This study reviewed the records of 35 patients who underwent electrophysiologic studies (EPS) and 39 RFCA procedures for EAT during a 10-year period. Of the 35 patients, 10 (28%) presented with decreased ventricular function and tachycardia-induced cardiomyopathy (TIC). The EAT originated on the right atrial side in 19 patients (54%) and on the left atrial side in the remaining 16 patients (46%). The right atrial sites included the right atrial appendage (RAA) (n = 9, 25%), the tricuspid annulus (n = 7, 20%), and the crista terminalis (n = 3). The left atrial sites included the left atrial appendage (LAA) (n = 6, 17%), the pulmonary veins (n = 5, 14%), the mitral annulus (n = 3), and the posterior wall of the left atrium (n = 2). The mechanism of all EAT probably is automaticity. All EATs could be abolished using RFCA. Follow-up data were available for all patients 2 to 8 years after RFCA. All 35 patients remained recurrence free, and ventricular function improved for all 10 patients with TIC. The origin of EAT in children differed from its origin in adults. The authors conclude that RFCA is a safe and effective treatment option for children with refractory EAT and should be considered early in the course of their illness

Reduced dietary salt for prevention of cardiovascular disease

: Restricting sodium intake in elevated blood pressure over short periods of time reduces blood pressure. Long term effects (on mortality, morbidity or blood pressure) of advice to reduce salt in patients with elevated or normal blood pressure are unclear. : To assess in adults the long term effects (mortality, cardiovascular events, blood pressure, quality of life, weight, urinary sodium excretion, other nutrients and use of anti-hypertensive medications) of advice to restrict dietary sodium using all relevant randomised controlled trials. : The Cochrane Library, MEDLINE, EMBASE, bibliographies of included studies and related systematic reviews were searched for unconfounded randomised trials in healthy adults aiming to reduce sodium intake over at least 6 months. Attempts were made to trace unpublished or missed studies and authors of all included trials were contacted. There were no language restrictions. : Inclusion decisions were independently duplicated and based on the following criteria: 1) randomisation was adequate; 2) there was a usual or control diet group; 3) the intervention aimed to reduce sodium intake; 4) the intervention was not multifactorial; 5) the participants were not children, acutely ill, pregnant or institutionalised; 6) follow-up was at least 26 weeks; 7) data on any of the outcomes of interest were available. : Decisions on validity and data extraction were made independently by two reviewers, disagreements were resolved by discussion or if necessary by a third reviewer. Random effects meta-analysis, sub-grouping, sensitivity analysis and meta-regression were performed. : Three trials in normotensives (n=2326), five in untreated hypertensives (n=387) and three in treated hypertensives (n=801) were included, with follow up from six months to seven years. The large, high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported; only 17 deaths equally distributed between intervention and control groups occurred. Systolic and diastolic blood pressures were reduced at 13 to 60 months in those given low sodium advice as compared with controls (systolic by 1.1 mm Hg, 95% CI 1.8 to 0.4, diastolic by 0.6 mm hg, 95% CI 1.5 to -0.3), as was urinary 24 hour sodium excretion (by 35.5 mmol/ 24 hours, 95% CI 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. People on anti-hypertensive medications were able to stop their medication more often on a reduced sodium diet as compared with controls, while maintaining similar blood pressure control. : Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. Evidence from a large and small trial showed that a low sodium diet helps in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.<br/

Measuring Residual Renal Function in Hemodialysis Patients without Urine Collection

This is the peer reviewed version of the following article: Wong, J., Kaja Kamal, R. M., Vilar, E. and Farrington, K. (2017), 'Measuring Residual Renal Function in Hemodialysis Patients without Urine Collection', Seminars in Dialysis, Vol. 30 (1): 39–49, which has been published in final form at doi: 10.1111/sdi.12557. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. © 2016 Wiley Periodicals, Inc.Many patients on hemodialysis retain significant residual renal function (RRF) but currently measurement of RRF in routine clinical practice can only be achieved using inter-dialytic urine collections to measure urea and creatinine clearances. Urine collections are difficult and inconvenient for patients and staff, and therefore RRF is not universally measured. Methods to assess RRF without reliance on urine collections are needed since RRF provides useful clinical and prognostic information and also permits the application of incremental hemodialysis techniques. Significant efforts have been made to explore the use of serum based biomarkers such as cystatin C, β-trace protein and β2 -microglobulin to estimate RRF. This article reviews blood-based biomarkers and novel methods using exogenous filtration markers which show potential in estimating RRF in hemodialysis patients without the need for urine collection.Peer reviewedFinal Accepted Versio

Antihypertensive withdrawal for the prevention of cognitive decline

Item does not contain fulltextClinical trials and observational data have variously shown a protective, harmful or neutral effect of antihypertensives on cognitive function. In theory, withdrawal of antihypertensives could improve cerebral perfusion and reduce or delay cognitive decline. However, it is also plausible that withdrawal of antihypertensives may have a detrimental effect on cognition through increased incidence of stroke or other vascular events. To assess the effects of complete withdrawal of at least one antihypertensive medication on incidence of dementia, cognitive function, blood pressure and other safety outcomes in cognitively intact and cognitive impaired adults. We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP on 12 December 2015. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search. We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) provided they compared withdrawal of antihypertensive medications with continuation of the medications and included an outcome measure assessing cognitive function or a clinical diagnosis of dementia. We included studies with healthy participants, but we also included studies with participants with all grades of severity of existing dementia or cognitive impairment. Two review authors examined titles and abstracts of citations identified by the search for eligibility, retrieving full texts where needed to identify studies for inclusion, with any disagreement resolved by involvement of a third author. Data were extracted independently on primary and secondary outcomes. We used standard methodological procedures expected by Cochrane.The primary outcome measures of interest were changes in global and specific cognitive function and incidence of dementia; secondary outcomes included change in systolic and diastolic blood pressure, mortality, adverse events (including cardiovascular events, hospitalisation and falls) and adherence to withdrawal. The quality of the evidence was evaluated using the GRADE approach. We included two RCTs investigating withdrawal of antihypertensives in 2490 participants. There was substantial clinical heterogeneity between the included studies, therefore we did not combine data for our primary outcome. Overall, the quality of included studies was high and the risk of bias was low. Neither study investigated incident dementia.One study assessed withholding previously prescribed antihypertensive drugs for seven days following acute stroke. Cognition was assessed using telephone Mini-Mental State Examination (t-MMSE) and Telephone Interview for Cognitive Status (TICS-M) at 90 days as a secondary outcome. The t-MMSE score was a mean of 1.0 point higher in participants who withdrew antihypertensive medications compared to participants who continued them (95% confidence interval (CI) 0.35 to 1.65; 1784 participants) and the TICS-M was a mean of 2.10 points higher (95% CI 0.69 to 3.51; 1784 participants). However, in both cases the evidence was of very low quality downgraded due to risk of bias, indirectness and evidence from a single study. The other study was community based and included participants with mild cognitive impairment. Drug withdrawal was for 16 weeks. Cognitive performance was assessed using a composite of at least five out of six cognitive tests. There was no evidence of a difference comparing participants who withdrew antihypertensive medications and participants who continued (mean difference 0.02 points, 95% CI -0.19 to 0.21; 351 participants). This evidence was of low quality and was downgraded due to risk of bias and evidence from single study.In one study, the systolic blood pressure after seven days of withdrawal was 9.5 mmHg higher in the intervention compared to the control group (95% CI 7.43 to 11.57; 2095 participants) and diastolic blood pressure was 5.1 mmHg higher (95% CI 3.86 to 6.34; 2095 participants). This evidence was low quality, downgraded due to indirectness, because the data must be interpreted in the context of the wider study looking at glyceryl trinitrate administration or not, and evidence from a single study. In the other study, systolic blood pressure increased by 7.4 mmHg in the withdrawal group compared to the control group (95% CI 7.08 to 7.72; 356 participants) and diastolic blood pressure increased by 2.6 mmHg (95% CI 2.42 to 2.78; 356 participants). This was moderate quality evidence, downgraded as evidence was from a single study. We combined data for mortality an