Monitoring for brain injury during ECMO

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Abstract

Objective

To determine if, in children, plasma glial fibrillary acidic protein (GFAP) is associated with brain injury during extracorporeal membrane oxygenation (ECMO) and with mortality.

Design

Prospective, observational study.

Setting

Pediatric intensive care unit in an urban tertiary care academic center.

Patients

Neonatal and pediatric ECMO patients (n=22).

Interventions

Serial blood sampling for GFAP measurements.

Measurements and Main Results

Prospective patients age 1 day-18 years who required ECMO from April 2008 to August 2009 were studied. GFAP was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 years) and 59 NICU infants without neurologic injury. In controls, the median GFAP concentration was 0.055 ng/mL (IQR: 0-0.092 ng/mL) and the 95th percentile of GFAP was 0.436ng/mL. In ECMO patients, plasma GFAP was measured at 6, 12 and every 24 hours after cannulation. We enrolled 22 children who underwent ECMO. Median age was 7 days (IQR, 2 days-9 years), and primary ECMO indication was: cardiac failure, 6/22 (27.3%), respiratory failure, 12/22 (54.5%), ECPR, 3/22 (13.6%), and sepsis, 1/22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. In the ECMO group, peak GFAP levels were higher in children with brain injury than those without (median, 5.9 vs 0.09ng/mL, p=0.04) and in non-survivors compared to survivors to discharge (median, 5.9 vs 0.09ng/mL, p=0.04). The odds ratio (OR) for brain injury for GFAP >0.436ng/mL vs normal was 11.5 (95%CI: 1.3-98.3) and the OR for mortality was 13.6 (95%CI: 1.7-108.5).

Conclusions

Pediatr Crit Care Med. 2011 September; 12(5): 572–579.

doi:  10.1097/PCC.0b013e3181fe3ec7

PMCID: PMC3686089

Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation

Bembea, MM, Savage W, Strouse JJ, et al.

Patients age 1 day-18 years who required ECMO from April 2008 to August 2009 were studied. 

GFAP was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 years) and 59 NICU infants without neurologic injury. 

In controls, the median GFAP concentration was 0.055 ng/mL (IQR: 0-0.092 ng/mL) and the 95th percentile of GFAP was 0.436ng/mL. 

In ECMO patients, plasma GFAP was measured at 6, 12 and every 24 hours after cannulation. 

We enrolled 22 children who underwent ECMO. Median age was 7 days (IQR, 2 days-9 years), and primary ECMO indication was: cardiac failure, 6/22 (27.3%), respiratory failure, 12/22 (54.5%), ECPR, 3/22 (13.6%), and sepsis, 1/22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. 

In the ECMO group, peak GFAP levels were higher in children with brain injury than those without (median, 5.9 vs 0.09ng/mL, p=0.04) and in non-survivors compared to survivors to discharge (median, 5.9 vs 0.09ng/mL, p=0.04). 

The odds ratio (OR) for brain injury for GFAP >0.436ng/mL vs normal was 11.5 (95%CI: 1.3-98.3) and the OR for mortality was 13.6 (95%CI: 1.7-108.5).

Conclusions

High GFAP during ECMO is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of ECMO patients to improve outcomes and benchmark new therapies.

Adult guidelines (Released online on 11/12/13)

Beware, this is for adults. Pediatric guidelines came out in late 2011.

1) Blood cholesterol therapy

2) Life style management to reduce CV risk

3) Management of overweight adult

3) Assessment of CV risk

Practice Guidelines

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Neil J. Stone, et al. J Am Coll Cardiol. Published online November 12, 2013. doi:10.1016/j.jacc.2013.11.002

2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Robert H. Eckel, et al. J Am Coll Cardiol. Published online November 12, 2013. doi:10.1016/j.jacc.2013.11.003

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society

Michael D. Jensen, et al. J Am Coll Cardiol. Published online November 12, 2013. doi:10.1016/j.jacc.2013.11.004

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

David C. Goff, et al. J Am Coll Cardiol. Published online November 12, 2013. doi:10.1016/j.jacc.2013.11.005

Post-Fontan thrombotic complications

J Am Coll Cardiol. 2013 Jan 22;61(3):346-53. doi: 10.1016/j.jacc.2012.08.1023. Epub 2012 Dec 12.

Factors associated with thrombotic complications after the Fontan procedure: a secondary analysis of a multicenter, randomized trial of primary thromboprophylaxis for 2 years after the Fontan procedure.

McCrindle BW, Manlhiot C, Cochrane A, Roberts R, Hughes M, Szechtman B, Weintraub R, Andrew M, Monagle P; Fontan Anticoagulation Study Group.

Source

Labatt Family Heart Centre, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. brian.mccrindle@sickkids.ca

Abstract

OBJECTIVES:

The study sought to identify factors associated with increased risk of thrombosis after Fontan.

BACKGROUND:

The Fontan procedure is the culmination of staged palliation for patients with univentricular physiology. Thrombosis is an important complication after this procedure.

METHODS:

An international multicenter randomized controlled trial of acetylsalicylic acid versus warfarin for thromboprophylaxis after the Fontan procedure was conducted in 111 patients, and did not show a significant difference regarding thrombotic complications. We performed a secondary analysis of this previously published manuscript to identify factors associated with thrombosis in this population. Standardized prospective data collection included independent adjudication of all events.

RESULTS:

At 2.5 years after randomization, time-related freedom from thrombosis was 69% (all venous, no arterial events), with 28% of thrombosis presenting with clinical signs or events. Hazard of thrombosis was highest immediately after Fontan with a gradual increase in risk during late follow-up. In multivariable models, factors associated with higher risk of thrombosis were pulmonary atresia with intact ventricular septum (hazard ratio [HR]: 3.64, 95% confidence interval [CI]: 1.04 to 12.70, p = 0.04), pulmonary artery distortion (HR: 2.35, 95% CI: 0.96 to 5.73, p = 0.06), lower pre-operative unconjugated bilirubin (HR: 0.84 μmol/l, 95% CI: 0.72 to 0.99, p = 0.04), use of central venous lines for >10 days or until hospital discharge (HR: 17.8, 95% CI: 3.97 to 79.30, p < 0.001), and lower FiO(2) 24 h after the procedure (HR: 0.67/10%, 95% CI: 0.45 to 1.00, p = 0.06). Patients on warfarin who consistently achieved minimum target international normalized ratio levels or those on acetylsalicylic acid had a decrease in risk of thrombosis compared with patients who often failed to meet target international normalized ratio level (HR: 3.53, 95% CI: 1.35 to 9.20, p = 0.01).

CONCLUSIONS:

More favorable thromboprophylaxis strategies are needed in light of the difficulties in controlling warfarin therapy and the high prevalence of thrombosis in this population.

Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comment in

• An aspirin a day... [J Am Coll Cardiol. 2013]

Dabigatran vs. Warfarin for Mechanical Heart Valves

ORIGINAL ARTICLE

Dabigatran versus Warfarin in Patients with Mechanical Heart Valves

J.W.Eikelboom et al.

NEJM 2013;369:1206-1214

BACKGROUND

Dabigatran is an oral direct thrombin inhibitor that has been shown to be an effective alternative to warfarin in patients with atrial fibrillation. We evaluated the use of dabigatran in patients with mechanical heart valves.

METHODS

In this phase 2 dose-validation study, we studied two populations of patients: those who had undergone aortic- or mitral-valve replacement within the past 7 days and those who had undergone such replacement at least 3 months earlier. Patients were randomly assigned in a 2:1 ratio to receive either dabigatran or warfarin. The selection of the initial dabigatran dose (150, 220, or 300 mg twice daily) was based on kidney function. Doses were adjusted to obtain a trough plasma level of at least 50 ng per milliliter. The warfarin dose was adjusted to obtain an international normalized ratio of 2 to 3 or 2.5 to 3.5 on the basis of thromboembolic risk. The primary end point was the trough plasma level of dabigatran.

RESULTS

The trial was terminated prematurely after the enrollment of 252 patients because of an excess of thromboembolic and bleeding events among patients in the dabigatran group. In the as-treated analysis, dose adjustment or discontinuation of dabigatran was required in 52 of 162 patients (32%). Ischemic or unspecified stroke occurred in 9 patients (5%) in the dabigatran group and in no patients in the warfarin group; major bleeding occurred in 7 patients (4%) and 2 patients (2%), respectively. All patients with major bleeding had pericardial bleeding.

CONCLUSIONS

The use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications, as compared with warfarin, thus showing no benefit and an excess risk. (Funded by Boehringer Ingelheim; ClinicalTrials.gov numbers, NCT01452347 and NCT01505881.)

Coffee consumption and heart health

JACC 2013;62:1043-51

State of the art review article

Hyperlipidemia: Triglyceride to HDL ratio

Triglyceride to HDL-C Ratio and Increased Arterial Stiffness in Children, Adolescents, and Young Adults
Pediatrics 2013 Apr 1;113:e1082-e1090.

Elaine M. Urbina, MD, et al. Cincinnati.
BACKGROUND AND OBJECTIVE: Lipid levels are linked to early atherosclerosis. Risk stratification may be improved by using triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), which relates to arterial stiffness in adults. We tested whether TG/HDL-C was an independent predictor of arterial stiffness in youth.

METHODS: Subjects 10 to 26 years old (mean 18.9 years, 39% male, 56% non-Caucasian, n = 893) had laboratory, anthropometric, blood pressure, and arterial stiffness data collected (brachial distensibility, augmentation index, carotid-femoral pulse-wave velocity). Subjects were stratified into tertiles of TG/HDL-C (low, n = 227; mid, n = 288; high, n = 379).

RESULTS: There was a progressive rise in cardiovascular (CV) risk factors and arterial stiffness across TG/HDL-C ratio. The high TG/HDL-C ratio group had the stiffest vessels (all P < .03 by analysis of variance). TG/HDL-C as a continuous variable was an independent determinant of brachial distensibility in CV risk factor adjusted model and for carotid-femoral pulse-wave velocity in obese subjects, with trend for higher augmentation index.

CONCLUSIONS: TG/HDL-C, an estimate of small, dense low-density lipoprotein cholesterol, is an independent determinant of arterial stiffness in adolescents and young adults, especially in obese youth. These data suggest that use of TG/HDL-C may be helpful in identifying young adults requiring aggressive intervention to prevent atherosclerotic CV diseases.

Berlin Heart

• Circulation 2013;127:1702-11
• Pediatric Cardiology

Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children

1. Christopher S. Almond, MD, MPH*; et al.

1. From Boston Children’s Hospital, Boston, MA (C.S.A.); Cincinnati Children’s Hospital, Cincinnati, OH (D.L.M.); Heart and Vascular Institute and Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (E.H.B., L.T.); Riley Hospital for Children, Indianapolis, IN (M.W.T.); Arkansas Children’s Hospital, Little Rock (M.I.); Stollery Children’s Hospital, Edmonton, AB, Canada (M.P.M., H.B.); Vanderbilt University Medical Center, Nashville, TN (L.C.J.); C.S. Mott Children’s Hospital, Ann Arbor, MI (E.J.D.); Children’s Hospital of Philadelphia, Philadelphia, PA (C.R.); Children’s Healthcare of Atlanta, Atlanta, GA (K.R.K.); University of Alabama at Birmingham, Birmingham (W.H.); Berlin Heart, Inc, The Woodlands, TX (R.K., C.T.); Children’s Hospital and Regional Medical Center Seattle, Seattle, WA (G.A.C.); University of Minnesota, Minneapolis (J.D.S.L.); Mount Sinai, New York, NY (K.N.); Medical College of Wisconsin, Milwaukee (R.A.N.); Children’s Hospital of Michigan, Detroit (H.L.W.); Mattel Children’s Hospital UCLA, Los Angeles, CA (B.R.); Children’s Hospital of Pittsburgh, Pittsburgh, PA (P.D.W.); Stanford University, Palo Alto, CA (O.R.); Children’s Medical Center Dallas, Dallas, TX (K.J.G.); Children’s Hospital Colorado, Aurora (M.B.M.); University of Florida, Gainesville (M.S.B.); St. Louis Children’s Hospital, St. Louis, MO (C.E.C.); and The Hospital for Sick Children, Toronto, ON, Canada (T.H.). Dr Morales was formerly at the Texas Children’s Hospital, Houston.

1. Correspondence to Christopher S. Almond, MD, MPH, The Heart Center, Boston Children’s Hospital, Department of Pediatrics, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115. E-mailchristopher.almond@childrens.harvard.edu

1. Abstract

Background—Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection.

Methods and Results—This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device (47 centers; May 2007 to Dec 2010). n = 204 children. Median duration of support was 40 days (range, 1–435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death.

Conclusions—Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

PFO closure - North American Trial. No significant benefit. But...

ORIGINAL ARTICLE

NEJM - online first

Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke

John D. Carroll, M.D., Jeffrey L. Saver, M.D., David E. Thaler, M.D., Ph.D., Richard W. Smalling, M.D., Ph.D., Scott Berry, Ph.D., Lee A. MacDonald, M.D., David S. Marks, M.D., and David L. Tirschwell, M.D. for the RESPECT Investigators

N Engl J Med 2013; 368:1092-1100March 21, 2013DOI: 10.1056/NEJMoa1301440

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BACKGROUND

Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age.

METHODS

In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated.

RESULTS

We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased.

CONCLUSIONS

In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number,NCT00465270.)

PFO closure did not result in reduction in recurrent embolic events - Europe, Canada, Brazil & Australia

ORIGINAL ARTICLE

NEJM - online first

Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism

Bernhard Meier, M.D., Bindu Kalesan, Ph.D., Heinrich P. Mattle, M.D., Ahmed A. Khattab, M.D., David Hildick-Smith, M.D., Dariusz Dudek, M.D., Grethe Andersen, M.D., Reda Ibrahim, M.D., Gerhard Schuler, M.D., Antony S. Walton, M.D., Andreas Wahl, M.D., Stephan Windecker, M.D., and Peter Jüni, M.D. for the PC Trial Investigators

N Engl J Med 2013; 368:1083-1091March 21, 2013DOI: 10.1056/NEJMoa1211716

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BACKGROUND

The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy.

METHODS

We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population.

RESULTS

The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56).

CONCLUSIONS

Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number,NCT00166257.)

Mediterranean Diet Decreases CV events.

ORIGINAL ARTICLE
NEJM 2013 online first

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

Ramón Estruch, M.D., Ph.D., Emilio Ros, M.D., Ph.D., Jordi Salas-Salvadó, M.D., Ph.D., Maria-Isabel Covas, D.Pharm., Ph.D., Dolores Corella, D.Pharm., Ph.D., Fernando Arós, M.D., Ph.D., Enrique Gómez-Gracia, M.D., Ph.D., Valentina Ruiz-Gutiérrez, Ph.D., Miquel Fiol, M.D., Ph.D., José Lapetra, M.D., Ph.D., Rosa Maria Lamuela-Raventos, D.Pharm., Ph.D., Lluís Serra-Majem, M.D., Ph.D., Xavier Pintó, M.D., Ph.D., Josep Basora, M.D., Ph.D., Miguel Angel Muñoz, M.D., Ph.D., José V. Sorlí, M.D., Ph.D., José Alfredo Martínez, D.Pharm, M.D., Ph.D., and Miguel Angel Martínez-González, M.D., Ph.D. for the PREDIMED Study Investigators

February 25, 2013DOI: 10.1056/NEJMoa1200303

BACKGROUND

Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events.

Full Text of Background...

METHODS

In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.

Full Text of Methods...

RESULTS

A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.

Biological Pacemaker!

HCN2/SkM1 Gene Transfer Into Canine Left Bundle Branch Induces Stable, Autonomically Responsive Biological Pacing at Physiological Heart Rates ONLINE FIRST


Gerard J.J. Boink, MSc; et al.
Correspondence: Dr. Michael Rosen, Columbia University, Department of Pharmacology and Pediatrics, 630 West 168th Street, PH 7W-321, New York, New York 10032-3702

J Am Coll Cardiol. 2013;():. doi:10.1016/j.jacc.2012.12.031 .Published online Feb 7, 2013
Objectives This study sought to test the hypothesis that hyperpolarization-activated cyclic nucleotide–gated (HCN)–based biological pacing might be improved significantly by hyperpolarizing the action potential (AP) threshold via coexpression of the skeletal muscle sodium channel 1 (SkM1).

Background Gene-based biological pacemakers display effective in vivo pacemaker function. However, approaches used to date have failed to manifest optimal pacemaker properties, defined as basal beating rates of 60 to 90 beats/min, a brisk autonomic response achieving maximal rates of 130 to 160 beats/min, and low to absent electronic backup pacing.

Methods We implanted adenoviral SkM1, HCN2, or HCN2/SkM1 constructs into left bundle branches (LBB) or left ventricular (LV) epicardium of atrioventricular-blocked dogs.

Results During stable peak gene expression on days 5 to 7, HCN2/SkM1 LBB-injected dogs showed highly stable in vivo pacemaker activity superior to SkM1 or HCN2 alone and superior to LV-implanted dogs with regard to beating rates (resting approximately 80 beats/min; maximum approximately 130 beats/min), no dependence on electronic backup pacing, and enhanced modulation of pacemaker function during circadian rhythm or epinephrine infusion. In vitro isolated LV of dogs overexpressing SkM1 manifested a significantly more negative AP threshold.

Conclusions LBB-injected HCN2/SkM1 potentially provides a more clinically suitable biological pacemaker strategy than other reported constructs. This superiority is attributable to the more negative AP threshold and injection into the LBB.

American College of Cardiology Foundation | Journal of the American College of Cardiology | HCN2/SkM1 Gene Transfer Into Canine Left Bundle Branch Induces Stable, Autonomically Responsive Biological Pacing at Physiological Heart Rates

Renin-Angiotensin Graphic from Science

Source: en.wikipedia.org via Inez on Pinterest

American College of Cardiology Foundation | Journal of the American College of Cardiology | An Aspirin a Day …⁎⁎

American College of Cardiology Foundation | Journal of the American College of Cardiology | An Aspirin a Day …⁎⁎

American College of Cardiology Foundation | Journal of the American College of Cardiology | Factors Associated With Thrombotic Complications After the Fontan ProcedureA Secondary Analysis of a Multicenter, Randomized Trial of Primary Thromboprophylaxis for 2 Years After the Fontan Procedure

American College of Cardiology Foundation | Journal of the American College of Cardiology | Factors Associated With Thrombotic Complications After the Fontan ProcedureA Secondary Analysis of a Multicenter, Randomized Trial of Primary Thromboprophylaxis for 2 Years After the Fontan Procedure

Echo - Coronary artery dimensions in Non-Kawasaki febrile children

CIRCULATION CARDIOVASCULAR IMAGING.112.000159


Published online before print January 28, 2013,

doi: 10.1161/​CIRCIMAGING.112.000159


Coronary Artery Dimensions in Febrile Children without Kawasaki Disease

Juan-Carlos G. Muniz1, Kirsten Dummer1, Kimberlee Gauvreau1, Steven D. Colan1, David R. Fulton1 and Jane W. Newburger1*

Background—Coronary artery (CA) dilatation on echocardiography is a criterion for treatment with intravenous immunoglobulin for incomplete Kawasaki disease (KD). However, CA dimensions for febrile children are unknown. We compared CA dimensions in children with febrile illnesses other than KD to those of normal afebrile children and to KD patients.

Methods and Results—We performed echocardiograms in 43 patients who met the following inclusion criteria: (1) age 3 months to 18 years, (2) daily fever >38 °C for ≥96 hours, and (3) a diagnosis other than KD.
These subjects had mean CA z-scores greater than normative values (LMCA=0.66±0.75, P<0 .001="" ca="" lad="0.35±1.0," maximum="" p="0.03)." rca="0.28±0.81," z-score="" zmax="">2 was found in 2 subjects (osteomyelitis, Mycoplasma pneumonia).
Among demographic and laboratory measures, only higher platelet count was associated with greater LAD z-scores (P=0.004) and zMax (P=0.03).
Non-KD febrile subjects, compared to 144 KD patients, had smaller CA z-scores (P=0.04, P<0 .001="" 2.0="" 20="" 25="" 32="" 84="" 95="" 98="" a="" all="" and="" blood="" cell="" count="" cut-off="" distinguishing="" erythrocyte="" febrile="" for="" from="" had="" in="" kd="" lad="" lmca="" lower="" non-kd="" of="" p="" patients="" platelet="" rate="" rca="" respectively="" sedimentation="" sensitivity="" specificity="" was="" white="" zmax="2.5,">
Conclusions—This pilot study found that mean CA dimensions in children with non-KD febrile illnesses are larger than those in normative afebrile subjects but smaller than dimensions in patients with KD. Future studies should augment the available data on CA dimensions in children with more severe febrile illnesses.

Serial BNP - Useful or Not?

Circulation. 2013; 127: 509-516

Controversies in Cardiovascular Medicine

Are Serial BNP Measurements Useful in Heart Failure Management?

Serial Natriuretic Peptide Measurements Are Not Useful in Heart Failure Management: The Art of Medicine Remains Long

Akshay S. Desai, MD, MPH

Introduction

Natriuretic peptides, including B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP), have emerged as powerful markers of cardiovascular risk in patients with heart failure.1 Circulating natriuretic peptide (NP) levels add incremental prognostic value to standard clinical risk stratification algorithms for both ambulatory and hospitalized heart failure patients, with a steady increase in the risk of mortality and recurrent heart failure hospitalization as NT-proBNP levels rise above 1000 pg/mL. A systematic review of 19 studies of patients with heart failure demonstrated that for every 100-pg/mL rise in BNP concentration, there was a corresponding 35% increase in the relative risk of death...

Circulation. 2013; 127: 500-508
Are Serial BNP Measurements Useful in Heart Failure Management?

Serial Natriuretic Peptide Measurements Are Useful in Heart Failure Management

James L. Januzzi, Jr, MD; Richard Troughton, MD, PhD


Introduction

We have been asked to take the position that serial natriuretic peptide (NP) testing is useful for heart failure (HF) management. To do so, we primarily draw on our experience as physicians with active clinical practices replete with patients suffering from the diagnosis but also from our in-depth knowledge of NP testing and its strengths and weaknesses...

Echo Assessment of LV diastolic function in Children

CIRCULATION: CARDIOVASCULAR IMAGING


Published online before print January 23, 2013,

doi: 10.1161/​CIRCIMAGING.112.000175

Interpretation of Left Ventricular Diastolic Dysfunction in Children with Cardiomyopathy by Echocardiography: Problems and Limitations

Andreea Dragulescu, Luc Mertens and Mark K. Friedberg (Toronto)

Background:
Left ventricular diastolic dysfunction(DD) is a key determinant of outcomes in pediatric cardiomyopathy(CM), but remains very challenging to diagnose and classify. Adult paradigms and guidelines relating to DD are currently applied in children. However, it is unknown whether these are applicable to children with CM. We investigated the assessment of DD in children with CM using adult and pediatric echocardiographic criteria and tested whether recent adult guidelines are applicable to this population.

Methods and Results:
Three investigators independently classified diastolic function in 4 study groups: controls; dilated(DCM), hypertrophic(HCM) and restrictive(RCM) cardiomyopathy. Agreement between investigators, failure to classify DD and the reasons for diagnostic failure were determined. The usefulness of individual echo parameters to diagnose and classify DD was assessed. 175 children (0-18yrs) were studied. DD diagnostic criteria were discrepant in the majority of patients. Delayed relaxation was diagnosed in only 14% of HCM patients and never in DCM and RCM, with 50% of those patients having co-existing findings of elevated filling pressures. Many key parameters, such as mitral and pulmonary venous Doppler were not informative. Agreement between investigators for grading of diastolic dysfunction was poor (36% of CM patients).

Conclusions:
Assessment of DD in childhood cardiomyopathy seems inadequate using current guidelines. The large range of normal pediatric reference values allows diagnosis of diastolic dysfunction in only a small proportion of patients. Key echo parameters to assess DF are not sufficiently discriminatory in this population and discrepancies between criteria within individuals prevent further classification and result in poor inter-observer agreement.

Hyponatremia Management (Adult)

JAHA Accessed Jan 23, 2013
Review article

CPR Duration and Outcome in Children

Circulation 2013 - Epub on Jan 22, 2013

Duration of Cardiopulmonary Resuscitation and Illness Category Impact Survival and Neurologic Outcomes for In-hospital Pediatric Cardiac Arrests

Renee I. Matos et al.
Background-Pediatric cardiopulmonary resuscitation (CPR) for >20 minutes has been considered futile after pediatric in-hospital cardiac arrests. This concept has recently been questioned.


Methods and Results - 3419 children from 328 US and Canadian sites (Get With The Guidelines-Resuscitation sites). In-hospital cardiac arrests between January 2000 and December 2009.

Patients were stratified into 5 patient illness categories: surgical cardiac, medical cardiac, general medical, general surgical, and trauma.

Survival to discharge was 27.9%, but only 19.0% of all cardiac arrest patients had favorable neurological outcomes.

Between 1 and 15 minutes of CPR, survival decreased linearly by 2.1% per minute, and rates of favorable neurological outcome decreased by 1.2% per minute.

Adjusted probability of survival was 41% for CPR duration of 1 to 15 minutes and 12% for >35 minutes.

Among survivors, favorable neurological outcome occurred in 70% undergoing <15 60="" and="" cpr="" minutes="" of="" undergoing="">35 minutes.

Compared with general medical patients, surgical cardiac patients had the highest adjusted odds ratios for survival and favorable neurological outcomes, 2.5 (95% confidence interval, 1.8-3.4) and 2.7 (95% confidence interval, 2.0-3.9), respectively.

Conclusions-CPR duration was independently associated with survival to hospital discharge and neurological outcome. Among survivors, neurological outcome was favorable for the majority of patients. Performing CPR for >20 minutes is not futile in some patient illness categories.

Outcome of Arterial Switch Operation for d-TGA

Circulation. 2013; 127: 331-339

Cardiovascular Outcomes After the Arterial Switch Operation for D-Transposition of the Great Arteries

Paul Khairy, MD, PhD et al. Boston.

Single-institution retrospective cohort study (1983-1999). n=400.

Overall, 400 patients, 154 (38.3%) with a ventricular septal defect, 238 (59.5%) with an intact septum, and 9 (2.3%) with a Taussig-Bing anomaly, were followed for a median of 18.7 years. In perioperative survivors, overall and arrhythmia-free survival rates at 25 years were 96.7±1.8% and 96.6±0.1%, respectively.

Late mortality was predominantly a result of sudden deaths and myocardial infarction.

At 25 years, 75.5±2.5% remained free from surgical or catheter-based reintervention.

Freedom from an adverse cardiovascular event was 92.9±1.9% at 25 years. Independent predictors were a single right coronary artery (hazard ratio, 4.58; 95% confidence interval, 1.32-15.90), P=0.0166) and postoperative heart failure (hazard ratio, 6.93; 95% confidence interval, 1.57-30.62; P=0.0107).

At last follow-up, the left ventricular ejection fraction was 60.3±8.9%, 97.3% had class I symptoms, and 5.2% obstructive coronary artery disease. Peak oxygen uptake was 35.1±7.6 mL/kg/min (86.1±15.1% predicted), with a chronotropic index <80 10.3="" 3.2="" 3.4="" 34.2="" 6.6="" and="" at="" in="" least="" mild="" moderate="" more="" neoaortic="" present="" pulmonary="" regurgitation="" respectively="" stenosis="" than="" were="">
Conclusions—Long-term and arrhythmia-free survival is excellent after arterial switch operation. Although sequelae include chronotropic incompetence and neoaortic, pulmonary, and coronary artery complications, most patients maintain normal systolic function and exercise capacity.