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
Thursday, February 7, 2013
Sunday, February 3, 2013
Friday, February 1, 2013
Wednesday, January 30, 2013
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...
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...
Thursday, January 24, 2013
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.
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