IVC Development - Alexander Barry's hypothesis

Clin Anat. 2010 Apr;23(3):297-303. doi: 10.1002/ca.20930.
Fetal development of the retrohepatic inferior vena cava and accessory hepatic veins: Re-evaluation of the Alexander Barry's hypothesis.
Jin ZW, Cho BH, Murakami G, Fujimiya M, Kimura W, Yu HC.
Dept. of Surgery, Chonbuk National University Medical School, Jeonju, South Korea.

Abstract
The retrohepatic inferior vena cava (IVC) is commonly considered to originate from the right vitelline or omphalomesenteric vein. In contrast, Alexander Barry hypothesized that one of the hepatic veins grows to merge with the subcardinal vein and develops into the retrohepatic IVC. We re-examined fetal development of the retrohepatic IVC and other related veins using serial histological sections of 20 human fetuses between 6 and 16 weeks of gestation. At 6-7 weeks, when a basic configuration of the portal-hepatic vein systems had just been established, one of hepatic veins (i.e., the posterocaudal vein in the present study) had grown caudally to reach the posterocaudal surface of the liver, and notably, extended into the primitive right adrenal gland (five of the eight early-staged fetuses). Because the inferior right hepatic vein (IRHV) and retrohepatic IVC appeared at the same developmental stage, it is likely that any peripheral remnants of the posterocaudal vein would continue to function as primary drainage territory for the IRHV. The caudate vein developed rapidly in accordance with marked caudal and leftward extension of Spiegel's lobe at 12-16 weeks. Thin accessory hepatic veins developed later than the caudate vein and IRHV. The present results supported Barry's hypothesis.

Angiotensin Receptor Blocker for Marfan Syndrome

NEJM 2008;358:2787-95

(Click on image to enlarge)

18 pediatric patients were treated (17 received Lorsartan, 1 received Ibesartan).

Age range:1 -16 yrs (median age 6.5 yrs)

Duration of study: Median 6 yrs (~4 yrs before starting ARB & ~ 2 yrs after starting ARB)

Dose:

Losartan - started at 0.6 mg/kg/day x 3 wks. Then, gradually increased to 1.4 mg/kg/day.

Ibesartan - started at 1.4 mg/kg/day. Then, gradually increased to 2.0 mg/kg/day.

Check BUN, Creatinine, Electrolytes after 3 months.

Fasting may not be necessary before Lipid Profile

Link

Ultrafiltration vs. Diuretics for Cardiorenal Syndrome

Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome
Bradley Bart et al. NEJM Online (Nov 7, 2012)
Editorial on this article NEJM Online (Nov 7, 2012)

Background
Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function.

Methods
We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days.

Results

Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P=0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was −0.04±0.53 mg per deciliter (−3.5±46.9 μmol per liter) in the pharmacologic-therapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 μmol per liter) in the ultrafiltration group (P=0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P=0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P=0.03).

Conclusions
In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.)

Obesity: Role of Government & Policy

Circulation 2012;126:2345

Obesity : Role of Policy and Government in the Obesity Epidemic

Nicole L. Novak, MSc; Kelly D. Brownell, PhD


From the Rudd Center for Food Policy and Obesity, Department of Psychology, Department of Epidemiology and Public Health, Yale University, New Haven, CT.

(Click on image to enlarge)

Correspondence to Nicole L. Novak, Rudd Center for Food Policy and Obesity, 309 Edwards St, New Haven, CT 06511. E-mail nicole.l.novak@gmail.com.

In 2001, the Surgeon General's “Call to Action to Prevent and Decrease Overweight and Obesity”1 identified obesity as a key public health priority for the United States. Obesity rates were higher than ever, with 61% of adults nationwide overweight or obese. In the intervening years, several administrations have declared a commitment to deal with the problem, and the food industry has issued numerous pledges for change, yet the prevalence of overweight and obesity has risen further, to 68%.2 Children have been particularly affected; >19% of school-aged children were obese in 2007 to 2008 compared with just 6% in the late 1970s.3 Disease rates join high healthcare costs, so everyone is affected personally, economically, or both.4,5


A wide range of government policies and programs have been implemented, including the development of national clinical guidelines, nutrition labeling on packaged foods, education and social marketing efforts, and more recently, calorie labeling on restaurant menus and federal efforts to increase access and financing for fresh fruits and vegetables. However, most of these efforts focus on clinical and educational factors or on community interventions and, until recently, have rarely addressed environmental drivers of obesity. There is growing theoretical and scientific support for policies that intervene on environmental determinants of overeating. The implementation of some policies is facing resistance from the food and beverage industries.

SVT prophylaxis in infants: Digoxin vs. Propranolol

Circ Arrhythm Electrophysiol. 2012 Oct 1;5(5):984-91. doi: 10.1161/CIRCEP.112.972620. Epub 2012 Sep 8.


The Study of Antiarrhythmic Medications in Infancy (SAMIS): A Multicenter, Randomized Controlled Trial Comparing the Efficacy and Safety of Digoxin Versus Propranolol for Prophylaxis of Supraventricular Tachycardia in Infants.

Sanatani S, Potts JE, Reed JH, Saul JP, Stephenson EA, Gibbs KA, Anderson CC, Mackie AS, Ro PS, Tisma-Dupanovic S, Kanter RJ, Batra AS, Fournier A, Blaufox AD, Singh HR, Ross BA, Wong KK, Bar-Cohen Y, McCrindle BW, Etheridge SP.

Background- Supraventricular tachycardia (SVT) is one of the most common conditions requiring emergent cardiac care in children, yet its management has never been subjected to a randomized controlled clinical trial. The purpose of this study was to compare the efficacy and safety of the 2 most commonly used medications for antiarrhythmic prophylaxis of SVT in infants: digoxin and propranolol.

Methods and Results- A randomized, double-blind, multicenter study of infants <4 atrioventricular="atrioventricular" comparing="comparing" digoxin="digoxin" excluding="excluding" months="months" nodal="nodal" or="or" propranolol.="propranolol." reciprocating="reciprocating" reentrant="reentrant" svt="svt" tachycardia="tachycardia" with="with" wolff-parkinson-white="wolff-parkinson-white">The primary end point was recurrence of SVT requiring medical intervention.
Time to recurrence and adverse events were secondary outcomes.
Sixty-one patients completed the study, 27 randomized to digoxin and 34 to propranolol.
SVT recurred in 19% of patients on digoxin and 31% of patients on propranolol (P=0.25).
No first recurrence occurred after 110 days of treatment.
The 6-month recurrence-free status was 79% for patients on digoxin and 67% for patients on propranolol (P=0.34), and there were no first recurrences in either group between 6 and 12 months. There were no deaths and no serious adverse events related to study medication.

Conclusions- There was no difference in SVT recurrence in infants treated with digoxin versus propranolol. The current standard practice may be treating infants longer than required and indicates the need for a placebo-controlled trial.
Clinical Trial Registration Information- http://clinicaltrials.gov; NCT-00390546.

Balloon Pulmonary Valvuloplasty - Safety & Efficacy

Catheter Cardiovasc Interv. 2012 Oct 1;80(4):663-72.

Safety and efficacy of balloon pulmonary valvuloplasty: A Multicenter Experience.

Holzer RJ, Gauvreau K, Kreutzer J, Trucco SM, Torres A, Shahanavaz S, Bergersen L.

METHODS: Prospective data collection. C3PO Registry. Cases performed between 02/07 and 06/10 at eight institutions. The registry was queried for cases of isolated BPV.


RESULTS:
211 cases were included (45%, Less than 1 month old).

Procedural success was achieved in 91% procedures, being defined as one of the following:
   (i) post-BPV peak systolic valvar gradient to < 25 mm Hg (88%),
   (ii) decrease in gradient by 50% (79%), or
   (iii) reduction of RV/systemic pressure ratio by 50% (45%).

Procedural success was more common in neonates, when compared to older patients (96% vs. 87%, P = 0.03).

Procedure failure - Risk factors included (i) moderate or severe pulmonary valve thickening (OR 2.9, CI 1-8.3), and (ii) presence of supravalve PS (OR 9.6, CI 2.7-33.8).

Adverse events:
Low severity AEs (levels 1-2) occurred in 9% of patients.
Higher severity AEs (levels 3-5) occurred in 3% of patient.
No deaths.
Risk factors for any AE (levels 1-5) were (i) age below 1 month (OR 3.5, CI 1.3-8.9) and (ii) operator experience of less than 10 years (OR 3.8, CI 1.5-9.9).

CONCLUSIONS: Procedural success is common and AEs, especially higher severity AEs, are rare for BPV in patients with isolated PS. Results have improved considerably when compared to historical data.

© 2012 Wiley Periodicals Inc.

Zoll LifeVest

From http://www.lifevest.zoll.com/medical-professionals/lifevest-overview.asp

Articles on Single Ventricle Reconstruction Surgery from October 2012 issue of JTCVS

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Congenital Heart Disease

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Introduction to the Single Ventricle Reconstruction trial

Emile Bacha and Pedro del Nido

J Thorac Cardiovasc Surg 2012;144 880-881

http://jtcs.ctsnetjournals.org/cgi/content/extract/144/4/880?etoc





Risk factors for hospital morbidity and mortality after the Norwood

procedure: A report from the Pediatric Heart Network Single Ventricle

Reconstruction trial

Sarah Tabbutt, Nancy Ghanayem, Chitra Ravishankar, Lynn A. Sleeper, David

S. Cooper, Deborah U. Frank, Minmin Lu, Christian Pizarro, Peter Frommelt,

Caren S. Goldberg, Eric M. Graham, Catherine Dent Krawczeski, Wyman W. Lai,

Alan Lewis, Joel A. Kirsh, Lynn Mahony, Richard G. Ohye, Janet Simsic,

Andrew J. Lodge, Ellen Spurrier, Mario Stylianou, Peter Laussen Pediatric

Heart Network Investigators

J Thorac Cardiovasc Surg 2012;144 882-895

http://jtcs.ctsnetjournals.org/cgi/content/abstract/144/4/882?etoc





Interstage mortality after the Norwood procedure: Results of the

multicenter Single Ventricle Reconstruction trial

Nancy S. Ghanayem, Kerstin R. Allen, Sarah Tabbutt, Andrew M. Atz, Martha

L. Clabby, David S. Cooper, Pirooz Eghtesady, Peter C. Frommelt, Peter J.

Gruber, Kevin D. Hill, Jonathan R. Kaltman, Peter C. Laussen, Alan B.

Lewis, Karen J. Lurito, L. LuAnn Minich, Richard G. Ohye, Julie V.

Schonbeck, Steven M. Schwartz, Rakesh K. Singh, Caren S. Goldberg

Pediatric Heart Network Investigators

J Thorac Cardiovasc Surg 2012;144 896-906

http://jtcs.ctsnetjournals.org/cgi/content/abstract/144/4/896?etoc





Cause, timing, and location of death in the Single Ventricle Reconstruction

trial

Richard G. Ohye, Julie V. Schonbeck, Pirooz Eghtesady, Peter C. Laussen,

Christian Pizarro, Peter Shrader, Deborah U. Frank, Eric M. Graham, Kevin

D. Hill, Jeffrey P. Jacobs, Kirk R. Kanter, Joel A. Kirsh, Linda M.

Lambert, Alan B. Lewis, Chitra Ravishankar, James S. Tweddell, Ismee A.

Williams, Gail D. Pearson Pediatric Heart Network Investigators

J Thorac Cardiovasc Surg 2012;144 907-914

http://jtcs.ctsnetjournals.org/cgi/content/abstract/144/4/907?etoc





Variation in perioperative care across centers for infants undergoing the

Norwood procedure

Sara K. Pasquali, Richard G. Ohye, Minmin Lu, Jonathan Kaltman, Christopher

A. Caldarone, Christian Pizarro, Carolyn Dunbar-Masterson, J. William

Gaynor, Jeffrey P. Jacobs, Aditya K. Kaza, Jane Newburger, John F. Rhodes,

Mark Scheurer, Eric Silver, Lynn A. Sleeper, Sarah Tabbutt, James Tweddell,

Karen Uzark, Winfield Wells, William T. Mahle, Gail D. Pearson Pediatric

Heart Network Investigators

J Thorac Cardiovasc Surg 2012;144 915-921

http://jtcs.ctsnetjournals.org/cgi/content/abstract/144/4/915?etoc

Guidelines: Cardiovascular Risk Reduction in Children

Link to free full text (Pediatrics 2011;128(Suppl 5):S213-S256).

Extensive data on evidence of risk and comprehensive review of current treatment options for children.

Epidemiology: Prevalence of CHD in US

Prevalence of CHD in US

Poster presented at ACC 2012: (JACC 2012;59(Supplement 1):E787.

These numbers were derived by extrapolating data from Quebec population study (Circ 2007;115:163-72) & 2010 US Census data.

(Click on the image to enlarge)

Prevalence of CHD in Europe

(Circulation 2011;123:841-9)

Prevalence in Quebec

(Circulation 2007;115:163-72)

Scoring system to determine need for LA decompression

J Heart Lung Transplant. 2003 Aug;22(8):883-8.


Scoring system to determine need for balloon atrial septostomy for restrictive interatrial communication in infants with hypoplastic left heart syndrome.

Mulla NF, Osher AP, Beeson WL, Kuhn MA, Larsen RL.

SourceDepartment of Pediatrics, Division of Pediatric Cardiology, Loma Linda University Children's Hospital, Loma Linda, California 92534 , USA. nmulla@ahs.llumc.edu



Abstract

BACKGROUND: Restrictive interatrial communication (IAC) causes morbidity and mortality in infants with hypoplastic left heart syndrome awaiting cardiac transplantation. We sought to create a scoring system, based on echocardiographic and clinical findings, to serve as a guide for determining the need for balloon atrial septostomy (BAS).



METHODS: We retrospectively reviewed echocardiograms of 44 infants with hypoplastic left heart syndrome. Infants were studied from the time of admission to the final end-point of transplantation, Norwood procedure, or death. Seventeen infants underwent BAS for clinical indications of oxygen saturation <80% in room air. Data collected included age at BAS, maximum velocity (V(max)), and IAC diameter throughout the clinical course. We assigned higher IAC scores to smaller IAC diameter, greater V(max) through the IAC, and lower oxygen saturation value. The minimum score was 3, and the maximum score was 9.



RESULTS: Only 10% of infants with a score <6 at presentation required BAS, whereas 67% of those with scores > or =6 required BAS. Higher IAC scores at presentation were associated with earlier need for BAS (p = 0.04).



CONCLUSIONS: The IAC scoring system can serve as a reliable clinical guide for identifying infants with hypoplastic left heart syndrome who are likely to require BAS for relief of critically restrictive IAC while awaiting cardiac transplantation.

Endocarditis Prophylaxis 2007 Guidelines are right.

New study published online Circulation 2012 supports 2007 guidelines.
Be sure to check the editorial associated with this article.

This article is reviewed in theheart.org "heartwire" as well.

Biodegradable stents are equivalent to metal stents

Link

Fenaldopam

Journal List > BMC Anesthesiol > v.8; 2008		Formats: Abstract  |  Full Text  |  PDF (230K)
	BMC Anesthesiol. 2008; 8: 6. Published online 2008 October 6. doi:  10.1186/1471-2253-8-6 PMCID: PMC2576052 Copyright © 2008 Hammer et al; licensee BioMed Central Ltd. Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients Gregory B Hammer,1 Susan T Verghese,2 David R Drover,3 Myron Yaster,4 and Joseph R Tobin5 1Departments of Anesthesia and Pediatrics, Stanford University School of Medicine, Stanford, USA 2Departments of Anesthesia and Pediatrics, Children's National Medical Center, George Washington University School of Medicine, Washington, USA 3Department of Anesthesia, Stanford University School of Medicine, Stanford, USA 4Departments of Anesthesiology, Critical Care Medicine, and Pediatrics, Johns Hopkins University, Baltimore, USA 5Departments of Anesthesiology and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, USA Corresponding author. Gregory B Hammer: ham@stanford.edu; Susan T Verghese: sverghes@cnmc.org; David R Drover:ddrover@stanford.edu; Myron Yaster: myaster@jhmi.edu; Joseph R Tobin: jtobin@wfubmc.edu Received April 7, 2008; Accepted October 6, 2008. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  Other Sections▼ Abstract Background Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children. Methods Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints. Results Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined. Conclusion Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar

Chest Pain Assessment in Children

SCAMP - Standardized Clinical Assessment Management Plan

JAHA April 2012

Demographic variables, clinical characteristics, and cardiac testing in a historical cohort (n=406) of patients presenting to our outpatient division for initial evaluation of chest pain in the most recent pre-SCAMP calendar year (2009) to patients enrolled in the chest pain SCAMP (n=364).

Demographic variables including age at presentation, sex, and clinical characteristics were similar between groups.

Adherence to the SCAMP algorithm for echocardiography was 84%. Practice variation decreased significantly after implementation of the SCAMP (P<0.001).

The number of exercise stress tests obtained was significantly lower in the SCAMP-enrolled patients compared with the historic cohort (∼3% of patients versus 29%, respectively; P<0.001).

Similarly, there was a 66% decrease in utilization of Holter monitors and 75% decrease in the use of long-term event monitors after implementation of the chest pain SCAMP (P=0.003 and P<0.001, respectively).

The number of echocardiograms obtained was similar between groups.

Conclusions Implementation of a SCAMP for evaluation of pediatric chest pain has lead to a decrease in practice variation and resource utilization.

Fundoplication & Gastrostomy ...outcome of single ventricle

Keating JJ et al.

JTCVS 2012;143:891-895

1999=2007

n=155

32 (21%) had fundoplication &/or G-tube (24 had both. 7 had G-tube only).

65 (42%) were HLHS. 24 of 65 had Fundos &/or G-tube.

Need for fundo &/or Gtube was associated with lower transplant-free survival.

CLOSURE trial result (PFO closure for Stroke)

Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale

Anthony J. Furlan et al.

NEJM 2012;366:991-9

Results:
A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan–Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events.

Conclusions:
In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical).

Procedures: Pericardiocentesis

Emergency pericardiocentesis video from NEJM 2012;366:e17

Realtime 3D in Congenital Heart Disease

Echocardiography 2012;29:232-41

Real time three-dimensional echocardiography (RT3DE) has been increasingly used in the diagnosis and assessment of congenital heart disease. A growing body of literature suggests that this new technology can be used as an integrated approach to assess the morphology of simple and complex congenital heart defects, flow abnormality, and left, right, and single ventricular function both qualitatively and quantitatively. This review summarizes the available evidence for the use of RT3DE in each of these areas. Future technology refinement in RT3DE and development of practice guidelines will increase the utilization of this new technology as a valuable tool to compliment 2D echocardiography/Doppler in clinical care and research to improve the care and outcome of congenital heart disease. (Echocardiography 2012;29:232-241)

How To Define Congenital Heart Disease in Scientific Studies

Congenital Heart Disease 2011;7(1):46-49

Estimates of the prevalence of congenital heart defects (CHD) have been published over many years and from many regions. As they are based on different definitions of which cases to include in the CHD prevalence, published prevalence estimates vary substantially. With the increasing use of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population-based data on CHD may be used: etiology, planning of treatment, or obtain information on outcome, including mortality. For etiology studies, it is important to include terminations of pregnancy as well as all births with CHD. For mortality studies in live births, inclusion of preterm born infants with PDA will increase overall mortality of CHD. The Danish Register of Congenital Heart Disease is based on hospital discharge diagnoses and diagnoses from outpatient visits. To increase the validity of these data, extensive data cleaning has been carried out based on record review and knowledge on the discharge coding practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD.

Guidelines and Reviews on TAVI

Transcatheter Aortic Valve Implantation.
Resource center at Cardiosource.Org

PDE-5 inhibitors - Cardiac Uses

State-of-the-art Review: JACC 2012;59(1):9-15.

Bryan Schwartz et al.

Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynaud's phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases.

CLARINET trial

Wessel, D. et al.
(Presented at AHA 2010)

Background: Infants with cyanotic congenital heart disease (CCHD) palliated with a systemic-to-pulmonary artery (PA) shunt are at increased risk for shunt thrombosis and mortality.

Methods: We conducted a multi-center, randomized, double-blind, placebo-controlled trial to determine whether the addition of clopidogrel, 0.2mg/kg/day, to conventional therapy reduces all-cause mortality and shunt-related morbidity in infants with CCHD palliated with a PA shunt. The clopidogrel dose was selected to inhibit ADP-induced platelet aggregation by 30-50%, similar to the 75 mg adult dose. The primary efficacy outcome event was the first occurrence of any component of the composite endpoint of death, shunt thrombosis or a cardiac procedure before 120 days of age following an event considered of thrombotic nature. This event-driven trial conducted in 32 countries had 80% power to detect a 30% relative reduction in the primary event rate with 172 events and .05 overall type I error rate.

Results: 906 infants <3 months of age who had undergone a PA shunt were randomly assigned to receive clopidogrel (467, 51.5%) or placebo (439, 48.5%) in addition to conventional therapy. Median duration of treatment was 162 days. Concomitant aspirin was administered in 88% of subjects.

The primary composite outcome rate did not differ significantly between the clopidogrel vs. placebo groups: 19.1% vs. 20.5%, respectively, with relative risk reduction = 11.1% (95%CI: –19.2, 33.6; p=.43).

Components of the composite primary outcome, analyzed separately, also did not differ significantly between clopidogrel and placebo groups: mortality rate was 11.8% vs 13.9%; shunt thrombosis was 5.8% vs. 4.8%, and cardiac-related interventions occurred in 4.5% vs. 3.2%, respectively.
Clopidogrel treatment was not significantly beneficial within any subgroups, specific cardiac defect groups or shunt types. The percentage of subjects in the clopidogrel vs. placebo groups with any bleeding event (18.8% vs. 20.2%) and with severe bleeding events (4.1% vs. 3.4%) was similar.

Conclusion: Clopidogrel treatment of infants < 3 months of age with CCHD palliated with a PA shunt and predominantly receiving concomitant aspirin therapy does not reduce all-cause mortality or shunt-related morbidity.

PICOLO trial results

Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children
Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial
Jennifer S, Li et al. for the PICOLO Investigators

Circulation 2008;117:553-9

Background— Infants and young children with certain types of heart disease are at increased risk for thromboses. Clopidogrel 75 mg/d is used in adults to prevent thrombotic events. The dose to achieve similar platelet inhibition in children is unknown. The objectives of the present study were (1) to determine the dose of clopidogrel needed in infants and young children to achieve a mean 30% to 50% inhibition of 5-μmol/L ADP–induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and (2) to assess the safety and tolerability of clopidogrel in infants and young children.

Methods and Results— We performed a prospective, multicenter, randomized, placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 to 24 months) with a cardiac condition at risk for arterial thrombosis. Patients were randomized to clopidogrel versus placebo in a 3:1 ratio in 4 sequential groups (0.01, 0.10, 0.20, and 0.15 mg/kg) for 7 abd 28 days. Platelet aggregation was assessed at baseline and steady state by light-transmission aggregometry. Of 116 patients enrolled, 92 (50% neonates, 50% infants/toddlers) were randomized, and 73 completed the study. A total of 79% of the randomized and treated patients were taking aspirin.

Compared with placebo, clopidogrel 0.20 mg · kg−1 · d−1 resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. There was marked interpatient variability in the degree of platelet aggregation inhibition within each treatment-dose group and age group. No serious bleeding events occurred.

Conclusions— Clopidogrel 0.20 mg/kg/day in children 0 to 24 months of age achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Clopidogrel is well tolerated in infants and young children at this dose.

Risk Stratification in Brugada Syndrome

Results of PRELUDE (PRogrammed ELectrical stimUllation preDictive valuE) Registry.

SG Priori et al.

JACC 2012;59:37-45.

Study of 247 men (Median age 44 yrs, Range 18-72 yrs)

Results: During a median follow-up of 34 months, 14 arrhythmic events (4.5%) occurred (13 appropriate shocks of the implantable defibrillator, and 1 cardiac arrest). Programmed electrical stimulation performed with a uniform and pre-specified protocol induced ventricular tachyarrhythmias in 40% of patients: arrhythmia inducibility was not a predictor of events at follow-up (9 of 14 events occurred in noninducible patients). History of syncope and spontaneous type I ECG (hazard ratio [HR]: 4.20), ventricular refractory period <200 ms (HR: 3.91), and QRS fragmentation (HR: 4.94) were significant predictors of arrhythmias.

Conclusions: Our data show that VT/VF inducibility is unable to identify high-risk patients, whereas the presence of a spontaneous type I ECG, history of syncope, ventricular effective refractory period <200 ms, and QRS fragmentation seem useful to identify candidates for prophylactic implantable cardioverter defibrillator.

Radiation Dose

Use of dose-dependent follow-up protocol and mechanism to reduce patient and staff radiation exposure in congenital and structural interventions.
Sawdy JM, et al. Cath Cardiovasc Interv 2011;78:136-42
Editorial: Cath Cardiovasc Interv 2011;78:143-4

Cath: Balloon Pulmonary Valvuloplasty

Predictors of reintervention in neonates with critical PS or PA-IVS.

Ghassan Shaath et al.

Cath Cardiovasc Interv 2012;79:659-664.

n=43 babies.

Mean f-up 19 mo.

36% required reintervention after at mean age of 7.4 mo.

Predictors of reintervention were the following:

1) Diagnosis of PA-IVS

2) Hospital stay > 7.5 days

3) TR gradient > 43 mmHg on the day after intervention

All were statistically-derived parameters. No good clinical explanation in the paper.

From discussion secton:

Humpl et al.Circ 2003;108:826-32 reported reintervention was more likely if TV z-score was < -5.

Fedderly et al. JACC 1995;25:460-5 reintervention was less likely if TV annulus > 11 mm and PV annulus > 7 mm.

Alwi et al. Cardiol Young 2005;15:141-7. PDA stenting is suggested if if small RV and TV z-score between -2.5 and -4.5.

ARBs for Marfan Syndrome

NEJM 2008;358_2787-95 (Free full text)

Angiotension II blockade and aortic root dilatation in Marfan syndrome.

Deficiency of fibrillin-1 in extracellular matrix leads to excessive signalling by TGF-beta. This may be the pathogenic mechanism for phenotypic features - including aortic root dilatation (mouse model). ARBs are known to inhibit TGF-beta. Therefore, in this non-randomized study, 18 children - mean age 6.5 yrs, range 1-16 yrs - who showed progressive dilatation of aortic root in spite of beta-blocker therapy were given ARBs.

Losartan started at 0.6 mg/kg/day x 3 weeks. If no side effects, dose was slowly increased to 1.4 mg/kg/day. (If the patient was receiving calcium-channel blocker, it was stopped when Losartan was started).

Or
Irbesartan at 1.4 mg/kg/day, increased upto 2 mg/kg/day.

Progression of aortic root dilatation was greatly reduced. See figure 2 in the article.

Prominent C-V wave in Severe Tricuspid Regurgitation

NEJM 2012 (Click here to see video in NEJM website)

Original Fontan Operation

January 2012 issue of the journal:
(Note: Apparently, this image is meant for an article, to be published in April 2012 issue. So, further description in this issue about this figure).