bluuebunny/crossref_metadata_2025 huggingface dataset:
Transvenous Closure of Secundum Atrial Septal Defects
Authors: Sharafuddin Melhem J. A. , Gu Xiaoping , Titus Jack L. , Urness Myra , Cervera-Ceballos J. J. , Amplatz Kurt
Published: June 2012

Background
Our purpose was to evaluate a new prosthesis for percutaneous closure of secundum atrial septal defects (ASDs).

Methods and Results
Percutaneous closure of surgically created fossa ovalis ASD was attempted in 15 minipigs. The mean balloon-stretched ASD diameter was 12.3±2.3 mm (range, 10 to 16 mm). The self-expanding prosthesis was braided from 0.005-in Nitinol wires in the shape of two flat buttons with a short connecting waist with a diameter corresponding to that of the defect to be closed. Polyester filling was added to enhance thrombogenicity. Pulmonary arteriography with levo-phase was obtained before placement; immediately after placement; and at 1-week, 1-month, and 3-month follow-ups. Four animals were killed at 1 week, 1 month, and 3 months for histopathological correlation. Three deaths resulted from ventricular fibrillation (one during anesthesia and two during the placement procedure). Successful placement of the prosthesis was achieved in the remaining 12 animals. Overall immediate ASD closure on angiography occurred in 7 of 12 animals (all polyester-filled prostheses). Absent or trace shunt by angiography was present in 11 of 12 devices at 1 week, with the remaining one demonstrating a small shunt. All septal defects were completely closed at 1 month with the exception of one case in which delayed partial dislodgment of an undersized prosthesis into the right atrium had developed. Closure rate at 3 months was 100%. Neoendothelialization and fibrous incorporation of the prosthesis were completed within 1 to 3 months.

Conclusions
Effective and permanent occlusion of secundum ASDs is feasible with a device that offers the advantages of easy placement, self-centering, and repositionability.
Idiopathic Ventricular Fibrillation Induced With Vagal Activity in Patients Without Obvious Heart Disease
Authors: Kasanuki Hiroshi , Ohnishi Satoshi , Ohtuka Masato , Matsuda Naoki , Nirei Takashi , Isogai Reiko , Shoda Morio , Toyoshima Yukari , Hosoda Saichi
Published: June 2012

Background
Recently, idiopathic ventricular fibrillation (VF) has gained much attention. Although several subgroups have been described, its pathogenesis, mechanism, treatment, and prognosis remain unknown.

Methods and Results
We studied six cases of idiopathic VF with transient late r′ waves and ST elevation (late r′/ST elevation) in leads V
1
through V
3
. Late r′/ST elevation was augmented before and after VF episodes. Signal-averaged ECGs showed late potentials even when no late r′/ST elevation occurred. During late r′, a conduction delay was observed by use of body-surface maps at the anterior wall and outflow tract of the right ventricle without inhomogeneity of the repolarization phase. There was a decrease or total disappearance of late r′/ST elevation with isoproterenol, atropine, and exercise stress testing and induction or exacerbation with propranolol, edrophonium, and hyperventilation. VF was induced by programmed electrical stimulation in all cases but two, in which it was induced only after edrophonium injection. In two cases, VF was exacerbated by propranolol, and in all cases, it was uninducible with isoproterenol. Heart rate spectral analysis just before VF episodes showed a sudden rise in vagal activity in two cases. As the VF mechanism, a conduction delay exists at the anterior wall and outflow tract of the right ventricle that is possibly exacerbated by an abrupt rise in vagal activity, inducing random reentry that results in VF. Class I antiarrhythmic agents and β-blockers were ineffective for this VF. All subjects required implantable cardioverter-defibrillators.

Conclusions
We propose this VF associated with late r′/ST elevation in the precordial leads and influenced by vagal activity as a new possible mechanism of idiopathic VF.
Effects of the Nitric Oxide Donor Sodium Nitroprusside on Intracellular pH and Contraction in Hypertrophied Myocytes
Authors: Ito Nobuhiko , Bartunek Josef , Spitzer Kenneth W. , Lorell Beverly H.
Published: June 2012

Background
We compared the effects of the nitric oxide donor sodium nitroprusside (SNP) on intracellular pH (pH
i
), intracellular calcium concentration ([Ca
2+
]
i
) transients, and cell contraction in hypertrophied adult ventricular myocytes from aortic-banded rats and age-matched controls.

Methods and Results
pH
i
was measured in individual myocytes with SNARF-1, and [Ca
2+
]
i
transients were measured with indo 1 simultaneously with cell motion. Experiments were performed at 37°C in myocytes paced at 0.5 Hz in HEPES-buffered solution (extracellular pH=7.40). At baseline, calibrated pH
i
, diastolic and systolic [Ca
2+
]
i
values, and the amplitude of cell contraction were similar in hypertrophied and control myocytes. Exposure of the control myocytes to 10
−6
mol/L SNP caused a decrease in the amplitude of cell contraction (72±7% of baseline,
P
<.05) that was associated with a decrease in pH
i
(−0.10±0.03 U,
P
<.05) with no change in peak systolic [Ca
2+
]
i
. In contrast, in the hypertrophied myocytes exposure to SNP did not decrease the amplitude of cell contraction or cause intracellular acidification (−0.01±0.01 U, NS). The cGMP analogue 8-bromo-cGMP depressed cell shortening and pH
i
in the control myocytes but failed to modify cell contraction or pH
i
in the hypertrophied cells. To examine the effects of SNP on Na
+
-H
+
exchange during recovery from intracellular acidosis, cells were exposed to a pulse and washout of NH
4
Cl. SNP significantly depressed the rate of recovery from intracellular acidosis in the control cells compared with the rate in hypertrophied cells.

Conclusions
SNP and 8-bromo-cGMP cause a negative inotropic effect and depress the rate of recovery from intracellular acidification that is mediated by Na
+
-H
+
exchange in normal adult rat myocytes. In contrast, SNP and 8-bromo-cGMP do not modify cell contraction or pH
i
in hypertrophied myocytes.
Decreased Myocyte Tension Development and Calcium Responsiveness in Rat Right Ventricular Pressure Overload
Authors: Fan Dongsheng , Wannenburg Thomas , de Tombe Pieter P.
Published: June 2012

Background
The contractile dysfunction observed in end-stage myocardial hypertrophy has at its base an abnormality in myocyte function. However, whether depressed contractile function is related to an alteration in contractile protein function is presently unknown.

Methods and Results
Contractile force, tension, and calcium responsiveness were measured in single-skinned myocytes isolated from rats with right ventricular hypertrophy (RVH) and control rats. RVH was induced by pulmonary artery constriction for 36 weeks and was associated with significant myocyte hypertrophy. Myocytes were attached to micropipettes that extended from a force transducer and motor. Isometric force was measured over a wide range of calcium concentrations at two sarcomere lengths (SLs). Maximal force was increased in the RVH group: 1.20±0.10 versus 1.62±0.13 mg at SL=2.0 μm and 1.33±0.10 versus 1.84±0.15 mg at SL=2.3 μm (
P
<.05). Maximal tension, however, was reduced in the RVH group: 24.3±1.91 versus 37.5±2.92 mN/mm
2
at SL=2.0 μm and 27.4±1.78 versus 41.8±3.19 mN/mm
2
at SL=2.3 μm (
P
<.01). The concentration of calcium ions required for half-maximal activation was increased in the RVH group: 2.64±0.13 versus 3.47±0.22 μmol/L at SL=2.0 μm and 2.23±0.15 versus 2.86±0.18 μmol/L at SL=2.3 μm (
P
<.01). The slope of the force-calcium relationship (Hill coefficient) was decreased in the RVH group at SL=2.0 μm (4.3±0.4 versus 3.1±0.2,
P
=.04) but not at SL=2.3 μm (3.8±0.2 versus 3.6±0.2,
P
=NS).

Conclusions
These results suggest that the depressed cardiac function of end-stage myocardial hypertrophy may be due, in part, to altered contractile protein function.
Cardiac Imaging for Risk Stratification With Dobutamine-Atropine Stress Testing in Patients With Chest Pain
Authors: Geleijnse Marcel L. , Elhendy Abdou , van Domburg Ron T. , Cornel Jan H. , Rambaldi Riccardo , Salustri Alessandro , Reijs Ambroos E. M. , Roelandt Jos R. T. C. , Fioretti Paolo M.
Published: June 2012

Background
Pharmacological stress echocardiography and myocardial perfusion scintigraphy are used frequently for risk stratification in patients with suspected myocardial ischemia. However, their relative prognostic strength has never been explored.

Methods and Results
Two hundred twenty consecutive patients with chest pain (mean age, 60±12 years; 124 men, 115 with previous myocardial infarction) were studied with dobutamine-atropine stress echocardiography (ECHO) and simultaneous
99m
Tc sestamibi single photon emission computed tomography imaging (MIBI). Ischemia was defined as deterioration in left ventricular wall motion and reversible perfusion defects, respectively. ECHO was positive for ischemia in 76 and MIBI in 91 patients (agreement, 77%; κ=.51). During follow-up of 31±15 months, 24 patients had hard cardiac events (nonfatal myocardial infarction or cardiac death). By univariate analysis, age, history of congestive heart failure, and any abnormality or ischemia on ECHO or MIBI were associated with cardiac events. Multivariate analysis revealed that age, abnormal ECHO (odds ratio [OR], 18.9; 95% CI, 2.5 to 146.0) or MIBI (OR, 12.8; 95% CI, 1.7 to 98.3), and ischemia on ECHO (OR, 4.0; 95% CI, 1.6 to 9.9) or MIBI (OR, 3.0; 95% CI, 1.2 to 7.4) had independent predictive values. When ECHO was used as a first option, the addition of MIBI to all nonischemic ECHO studies decreased the OR from 4.0 (95% CI, 1.6 to 9.9) to 3.8 (95% CI, 1.4 to 10.2). Addition of MIBI confined to nonischemic ECHO studies in which target heart rate was not attained (nondiagnostic studies) increased the OR to a maximal 5.7 (95% CI, 2.2 to 15.0). In contrast, the addition of ECHO to nondiagnostic MIBI studies was not useful.

Conclusions
Dobutamine-atropine ECHO and MIBI provide comparable prognostic information. The addition of MIBI to ECHO may be useful in patients with nondiagnostic ECHO studies.
Beneficial Effects of Intravenous and Oral Carvedilol Treatment in Acute Myocardial Infarction
Authors: Basu Sumit , Senior Roxy , Raval Usha , van der Does Reinhard , Bruckner Thomas , Lahiri Avijit
Published: June 2012

Background
Evidence of efficacy and safety of β-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer β-blockers such as carvedilol have not been tested in this setting.

Methods and Results
This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo,
P
<.02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (
P
<.0001), blood pressure (
P
<.005) at rest, and rate-pressure product at peak exercise (
P
<.003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre–hospital discharge examination (63 versus 53 mL;
P
<.01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9;
P
<.001). In a subgroup with left ventricular ejection fraction <45% (n=49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling.

Conclusions
Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.
Risk Stratification After Myocardial Infarction Using Signal-Averaged Electrocardiographic Criteria Adjusted for Sex, Age, and Myocardial Infarction Location
Authors: Savard Pierre , Rouleau Jean-Lucien , Ferguson John , Poitras Nicole , Morel Patrick , Davies Richard F. , Stewart Duncan J. , Talajic Mario , Gardner Martin , Dupuis Robert , Lauzon Claude , Sussex Bruce , Potvin Louise , Warnica Wayne
Published: June 2012

Background
The objectives were to investigate the factors influencing signal-averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and to develop criteria for predicting arrhythmic events (AEs) that account for these factors.

Methods and Results
SAECGs were recorded 5 to 15 days after MI in 2461 patients without bundle-branch block. The duration (QRSd), terminal potential (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During follow-up (17±8 months), AEs (arrhythmic death; ventricular tachycardia, VT; ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating characteristic curves showed that QRSd discriminated patients with all types of AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also discriminated AE patients. Sex, age, and MI location significantly affected the SAECG; survivors without VT or VF were divided into subgroups (2 sex×4 age×2 MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall sensitivity and specificity but with less uniform values for each subgroup. A Cox model was constructed by use of multiple prognostic indicators, and in rank order, QRSd, previous MI, and Killip class were predictive of AEs.

Conclusions
SAECG adjustments for sex, age, and MI location did not improve sensitivity and specificity but produced a more uniform predictive performance. The proposed criteria are based only on QRSd, because late potentials (VRMS and LAS) did not discriminate patients with sudden death. Duration of high-level activity during QRS (QRSd−LAS) can predict AEs, suggesting that the arrhythmogenic substrate involves a large mass of myocardium.
Prorenin, Renin, Angiotensinogen, and Angiotensin-Converting Enzyme in Normal and Failing Human Hearts
Authors: Danser A. H. Jan , van Kesteren Catharina A. M. , Bax Willem A. , Tavenier Monique , Derkx Frans H. M. , Saxena Pramod R. , Schalekamp Maarten A. D. H.
Published: June 2012

Background
A local renin-angiotensin system in the heart is often invoked to explain the beneficial effects of ACE inhibitors in heart failure. The heart, however, produces little or no renin under normal conditions.

Methods and Results
We compared the cardiac tissue levels of renin-angiotensin system components in 10 potential heart donors who died of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin and prorenin in DCM patients were higher than in the donors. The cardiac and plasma levels of renin in DCM were positively correlated, and extrapolation of the regression line to normal plasma levels yielded a tissue level close to that measured in the donor hearts. The cardiac tissue-to-plasma concentration (T/P) ratios for renin and prorenin were threefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusion into the interstitial fluid. Cell membranes from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate consumption by cardiac renin.

Conclusions
These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.
Survival and Risk Factors for Death After Cardiac Transplantation in Infants
Authors: Canter Charles , Naftel David , Caldwell Randall , Chinnock Richard , Pahl Elfriede , Frazier Elizabeth , Kirklin James , Boucek Mark , Morrow Robert
Published: June 2012

Background
Despite the increasing application of cardiac transplantation in infants, reported survival rates vary, and risk factors for death are poorly understood.

Methods and Results
To examine early survival and risk factors for death in infants (<1 year of age) undergoing cardiac transplantation, 141 infants (36 <1 month of age) underwent primary cardiac transplantation between January 1, 1993, and January 1, 1995, at 23 centers in the Pediatric Heart Transplant Study (PHTS). Diagnoses were hypoplastic left heart syndrome (66%), other congenital heart disease (17%), cardiomyopathy (14%), and other (3%). Actuarial survival after cardiac transplantation was 84% at 1 month, 70% at 1 year, and 69% at 2 years, with the greatest hazard for death within the first 3 months. The principal cause of death was early graft failure in 20 patients (52% of deaths), infection in 10 (26% of deaths), and rejection in 4 (10%). On the basis of multivariate analysis, risk factors for early mortality were history of previous sternotomy (
P
=.0003), nonidentical blood type donor (
P
=.01), recipient non–blood group A (
P
=.02), and donor cause of death other than closed head trauma (
P
=.04). Diagnosis at listing, waiting time (mean, 1.3 months), graft ischemic time (mean, 228 minutes; range, 68 to 479 minutes), and recipient ventilatory or inotropic support at listing were not predictive for mortality after transplant.

Conclusions
The higher mortality rate observed with infant heart transplantation is due to a higher mortality within the first month after transplantation as a result of early graft failure. Strategies to improve donor heart function at implantation would have the greatest impact on survival after infant cardiac transplantation.
Low-Energy Cardioversion of Spontaneous Atrial Fibrillation
Authors: Lévy Samuel , Ricard Philippe , Gueunoun Max , Yapo Florence , Trigano Jacques , Mansouri Chadia , Paganelli Franck
Published: June 2012

Background
Recent studies have suggested that induced atrial fibrillation (AF) could be successfully terminated by using a two-catheter electrode system and low energy (<400 V). This study evaluated the efficacy and safety of low-energy cardioversion in spontaneous chronic and paroxysmal AF.

Methods and Results
Forty-two consecutive patients with spontaneous AF underwent low-energy electrical cardioversion. AF was chronic (≥1 month) with a mean duration of 9±19 months in 28 patients (group I) or paroxysmal with a history of recurrent attacks and a mean duration of the present episode of 7±16 days in 14 patients (group II). An underlying heart disease was present in 28 patients. A 3/3-ms biphasic shock was delivered between catheters positioned in the right atrium and the coronary sinus in 32 patients. In 10 patients, the left pulmonary artery branch was used. The catheters were connected to a custom external defibrillator. The shocks were synchronized to the R wave. Following a test shock of 60 V, the energy was increased in 40-V steps until a maximum of 400 V or restoration of sinus rhythm. Sinus rhythm was restored in 22 of the 28 patients (78%) of group I by using a mean leading-edge voltage of 297±57 V (mean energy, 3.3±1.3 J) and in 11 of 14 patients (78%) of group II by using a mean leading-edge voltage of 223±41 V (mean energy, 1.8±0.7 J). The energy required for terminating chronic AF was significantly (
P
<.001) higher than that required for terminating paroxysmal AF. Among the other variables studied, the duration of AF significantly affected the successful voltage. Ventricular proarrhythmia occurred in 1 patient with atrial flutter due to an unsynchronized shock. Of the 22 patients of group I in whom sinus rhythm was restored, 14 (63%) remained in sinus rhythm with a mean follow-up of 9±3 months. Pain level showed a good correlation with increasing voltage. However, a marked interindividual variation was noted.

Conclusions
Atrial defibrillation using low energy between two intracardiac catheters with an electrical field between the right and left atria and the protocol used is feasible in patients with persistent spontaneous AF. The technique is safe provided synchronization to the R wave is achieved. A low recurrence rate of AF was seen in patients in whom sinus rhythm was restored.
Coronary Artery Disease and Polymorphisms in a Receptor Mediating Shear Stress–Dependent Platelet Activation
Authors: Murata Mitsuru , Matsubara Yumiko , Kawano Koichi , Zama Takeru , Aoki Nobuo , Yoshino Hideaki , Watanabe Gentaro , Ishikawa Kyozo , Ikeda Yasuo
Published: June 2012

Background
Platelets play pivotal roles in coronary thrombosis, and antiplatelet therapies are widely used for coronary artery disease (CAD). However, the effects of genetic variation in platelets on CAD are poorly understood. We have assessed the association between CAD and polymorphisms in a platelet receptor for von Willebrand factor, the glycoprotein (GP) Ib/IX complex, which mediates shear stress–dependent platelet activation.

Methods and Results
Genotypes of the α-chain of the receptor (GP Ibα,
145
Thr/Met) were determined in 91 patients with myocardial infarction (MI) or angina pectoris whose lesions were confirmed by coronary angiography as well as in 105 individuals from the general population with no history of angina or other heart diseases and normal resting ECGs. There was no homozygote for Met/Met in either the control or patient groups. The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group. However, the frequency of T/M was significantly higher in patients aged ≤60 years (31.8%) than in control subjects aged ≤60 years (16.0%;
P
<.05, odds ratio=2.5). An association was also demonstrated between CAD and the other polymorphism of GP Ibα, a variable number of tandem repeats of a 13–amino acid sequence, which is known to be linked to the
145
Thr/Met polymorphism. There was an association between the frequency of the T/M genotype and the angiographic severity of CAD: 11.1% for Gensini score <40 versus 50.0% for Gensini score ≥40 (
P
=.0015). There was no difference in the distribution of GP Ibα genotypes between patients with MI and those with angina pectoris.

Conclusions
This study suggests that the presence of the Met allele in GP Ibα is a risk factor for the prevalence and severity of CAD in individuals aged ≤60 years. The results need to be confirmed in a large-scale study of incident case subjects and matching control subjects.
Increased Formation of the Isoprostanes IPF
2α
-I and 8-Epi-Prostaglandin F
2α
in Acute Coronary Angioplasty
Authors: Reilly Muredach P. , Delanty Norman , Roy Louis , Rokach Joshua , Callaghan Peter O. , Crean Peter , Lawson John A. , FitzGerald Garret A.
Published: June 2012

Background
The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the limitations of available indices of oxidant stress in vivo. Isoprostanes are stable, free radical–catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion via percutaneous transluminal coronary angioplasty (PTCA).

Methods and Results
We developed specific, mass spectrometry assays for two structurally distinct F
2
isoprostanes, 8-epi-PGF
2α
and IPF
2α
-I. Urine samples for isoprostane determination were collected in patients undergoing coronary arteriography (n=11), elective PTCA (n=15), and angiography after thrombolysis for acute myocardial infarction (MI) (n=10). Urinary levels (pmol/mmol creatinine) of both isoprostanes were markedly increased from baseline in the first 6 hours after PTCA for acute MI (105±17.8 versus 230±66 for 8-epi-PGF
2α
[
P
=.009] and 466±91 versus 833±153 for IPF
2α
-I [
P
=.001]) and returned toward preprocedural values by 24 hours (122±18 for 8-epi-PGF
2α
and 457±102 for IPF
2α
-I). There was a slight increase in urinary 8-epi-PGF
2α
levels (64.7±9.5 versus 84.9±10.6;
P
=.02) after diagnostic coronary arteriography and elective PTCA (88.7±7.5 versus 114.3±16.1;
P
=.01). A striking correlation was observed (
r
=.68,
P
<.0001; n=33) between urinary 8-epi-PGF
2α
and IPF
2α
-I levels in patients receiving thrombolytic agents for acute MI.

Conclusions
Urinary F
2
isoprostane levels are elevated in patients after treatments resulting in reperfusion for acute MI. These findings provide evidence consistent with increased oxidant stress in vivo in this setting. Measurement of urinary isoprostanes may offer a noninvasive approach to the assessment of oxidant stress and the efficacy of antioxidant therapies in these syndromes.
Influence of Infarct-Zone Viability on Left Ventricular Remodeling After Acute Myocardial Infarction
Authors: Bolognese Leonardo , Cerisano Giampaolo , Buonamici Piergiovanni , Santini Alberto , Santoro Giovanni M. , Antoniucci David , Fazzini Pier Filippo
Published: June 2012

Background
The relation between residual myocardial viability after acute myocardial infarction (AMI) and ventricular remodeling has yet to be fully elucidated. We hypothesized that the presence of residual viability would favorably influence left ventricular remodeling after AMI and that serial changes in left ventricular dimensions might be related to the extent of myocardial viability in the infarct zone.

Methods and Results
Ninety-three patients with a first AMI successfully treated with primary coronary angioplasty underwent two-dimensional echocardiography within 24 hours of admission and low-dose dobutamine echocardiography at a mean of 3 days after AMI. Two-dimensional echocardiography and coronary angiography were obtained in all patients 1 and 6 months after coronary angioplasty. On the basis of dobutamine echocardiography responses, patients were divided in two subsets: those with (n=48; group I) and those without (n=45; group II) infarct-zone viability. There was no difference in minimal lesion diameter and infarct-related artery patency at 1 and 6 months between the two groups. Group II patients had significantly greater end-diastolic (76±18 versus 53±14 mL/m
2
;
P
<.0003) and end-systolic (42±17 versus 22±11 mL/m
2
;
P
<.0003) volumes at 6 months than did patients in group I. The extent of infarct-zone viability was significantly inversely correlated with percent changes in end-diastolic volumes at 6 months (
r
=−.66;
P
<.000001) and was the most powerful independent predictor of late left ventricular dilation.

Conclusions
After reperfused AMI, the degree of left ventricular dilation, when it occurs, is inversely related to the extent of residual myocardial viability in the infarct zone. Thus, the absence of residual infarct-zone viability discriminates patients who develop progressive left ventricular dilation after reperfused AMI from those who maintain normal left ventricular geometry.
Regional Sympathetic Nervous Activity and Oxygen Consumption in Obese Normotensive Human Subjects
Authors: Vaz Mario , Jennings Garry , Turner Andrea , Cox Helen , Lambert Gavin , Esler Murray
Published: June 2012

Background
Disturbed sympathetic nervous function may be of importance in obesity; sympathetic underactivity could contribute to deficient thermogenesis, positive energy balance, and weight gain, while in contrast, sympathetic nervous overactivity would predispose to the development of obesity-related hypertension. Global indices of sympathetic nervous system (SNS) function such as plasma or urinary norepinephrine (NE) have been unable to define SNS status in obesity. Since regional SNS activity can be altered in the absence of global changes, we investigated SNS activity in the heart, kidneys, and hepatomesenteric bed in healthy human subjects across a wide body mass index (BMI) range of between 19.6 and 35.5.

Methods and Results
Whole-body and regional plasma NE kinetics using [
3
H]-labeled NE were assessed. Regional oxygen consumption was measured by combining arteriovenous differences in oxygen content and regional blood flow. Arterial plasma NE and whole-body plasma NE spillover were unrelated to BMI. With a BMI cutoff of 27, mean cardiac NE spillover was 46% lower in the obese subjects when compared with the lean subjects (
P
=.017). Renal NE spillover was significantly correlated with BMI (
r
=.668,
P
=.001), the mean value in the obese subjects being more than twice that in the lean subjects. Hepatomesenteric NE spillover was comparable in lean and obese subjects. Renal and hepatomesenteric oxygen consumption were both significantly higher in the obese subjects compared with lean subjects.

Conclusions
Regional SNS activity is heterogeneous in the obese state. Important regional alterations, which may be clinically relevant, occur in the absence of changes in global indices of sympathetic nervous function. The enhanced renal NE spillover in obesity may have implications for the development of hypertension in this group, whereas the low cardiac sympathetic tone would be expected to be cardioprotective. Enhanced visceral oxygen consumption evident in the kidneys and hepatomesenteric circulation in proportion to body mass contributes to the greater resting oxygen consumption in obesity.
Percutaneous Transluminal Mitral Valvuloplasty Normalizes Baroreflex Sensitivity and Sympathetic Activity in Patients With Mitral Stenosis
Authors: Ashino Kazuhiro , Gotoh Eiji , Sumita Shin-ichi , Moriya Akihiko , Ishii Masao
Published: June 2012

Background
In patients with mitral stenosis, reduced cardiac output or altered pulmonary hemodynamics may increase sympathetic nerve activity. However, the magnitude of the increase in sympathetic activity in such patients and the effect of valvuloplasty on this activity are unknown.

Methods and Results
We microneurographically measured muscle sympathetic nerve activity before and after mitral valvuloplasty in 10 patients (mean±SEM age, 48±2 years) with mitral stenosis and in 10 healthy volunteers (47±4 years); hemodynamic variables were also measured. Baroreflex sensitivity was assessed on the basis of the ratio of the change in heart rate or muscle sympathetic activity to the change in mean arterial pressure during intravenous infusion of sodium nitroprusside or phenylephrine. At baseline, muscle sympathetic activity was significantly higher in the patients with mitral stenosis than in the control subjects (42.1±3.2 versus 26.1±3.7 bursts/min,
P
<.05). However, there was no significant difference between the groups in sympathetic activity at 1 week after valvuloplasty. The reduction in sympathetic activity after valvuloplasty was maintained for ≥6 months and correlated with the increase in cardiac index (
r
=.74,
P
<.05). Baroreflex sensitivity was significantly lower in the patients than in the control subjects, but after valvuloplasty there was no significant difference in baroreflex sensitivity between the groups.

Conclusions
Sympathetic activity is increased in patients with mitral stenosis. Mitral valvuloplasty in such patients results in early and long-lasting normalization of sympathetic nerve activity, possibly because of an improvement in arterial baroreflex sensitivity.
Knowledge of Perfusion and Contractile Reserve Improves the Predictive Value of Recovery of Regional Myocardial Function Postrevascularization
Authors: Meza Mario F. , Ramee Stephen , Collins Tyrone , Stapleton Dwight , Milani Richard V. , Murgo Joseph P. , Cheirif Jorge
Published: June 2012

Background
This study was designed to determine the value of myocardial contrast echocardiography (MCE) and dobutamine echocardiography (DE), alone or in combination, in predicting functional recovery in patients with resting wall motion abnormalities due to CAD. MCE and DE have been independently shown to be useful in detecting myocardial viability in the post–myocardial infarction setting.

Methods and Results
Thirty-nine patients with significant coronary artery disease and resting wall motion abnormalities underwent DE (2.5 to 20 μg · kg
−1
· min
−1
) and wall motion analysis (16-segment model). MCE was performed with selective intracoronary injections of sonicated meglumine (2 cm
3
). Myocardial viability was defined as presence of contrast effect by MCE and contractile reserve or an ischemic response by DE. Functional recovery (improvement in wall motion) was assessed after revascularization (percutaneous transluminal coronary angioplasty, n=20; coronary artery bypass surgery, n=19). When the two groups of patients were analyzed, MCE was associated with excellent sensitivities (84%) yet poor specificities (19% to 26%); DE had lower sensitivities (79% to 80%) but also poor specificities (30% to 36%). The combination of both was associated with excellent sensitivities (90% to 93%) and modest specificities (48% to 50%) for predicting functional recovery. A biphasic response with DE was infrequent (14% to 42%) but highly specific of functional recovery (84% to 94%). MCE had an excellent negative predictive value for functional recovery (83%).

Conclusions
The prediction of functional recovery post-revascularization can be enhanced by combining MCE and DE.
Progressive Anterior Ablation in the Coronary Sinus Region
Authors: Krahn Andrew D. , Klein George J. , Yee Raymond , Basta Magdy N. , Lee John K.
Published: June 2012

Background
AV node modification is an emerging approach to rate control in patients with medically refractory atrial fibrillation. The mechanism of benefit of this procedure is not completely understood.

Methods and Results
Twenty-two patients (age, 65±11 years; 16 women) with medically refractory paroxysmal atrial fibrillation referred for complete AV node ablation underwent serial ablations beginning at the level of the coronary sinus os progressing in a superior and anterior direction toward the His bundle. Serial atrial extrastimulus testing was performed to determine the effect of the progressive posteroseptal ablation in the region of the coronary sinus on the AV node antegrade refractory curve. Two of 22 patients had antegrade dual AV node pathways before ablation. Three patterns of response to serial ablation were noted. In 10 patients (45%), loss of the terminal portion of the AV node antegrade refractory curve occurred without evidence of fast pathway injury. In 7 patients (32%) the curve was shifted upward and to the left, consistent with nonspecific AV node damage. In 5 patients (23%), no effect could be attained before induction of complete AV block at superior and anterior ablation sites. Clinical variables and site of ablation did not predict response to serial ablations.

Conclusions
These data suggest that the mechanism of benefit of AV node modification in this population may be through elimination of “slow pathway” tissue in half of patients and nonspecific injury in the remainder. Modification without complete AV block may not be possible in a minority of patients, as the response to progressive ablation appears to be “all or none” conduction.
Radiofrequency Catheter Ablation of Postinfarction Ventricular Tachycardia
Authors: Rothman Steven A. , Hsia Henry H. , Cossú Sergio F. , Chmielewski I. Lisa , Buxton Alfred E. , Miller John M.
Published: June 2012

Background
Radiofrequency (RF) catheter ablation is effective therapy for monomorphic ventricular tachycardia (VT) in patients without structural heart disease. In patients with postinfarction VT; however, this procedure has been used predominantly as adjunctive therapy, targeting only the patient’s clinically documented arrhythmia. By targeting all inducible, sustained VT morphologies, we sought to determine the utility of RF catheter ablation as a primary cure in patients who present with hemodynamically tolerated VT.

Methods and Results
RF ablation was attempted in 35 patients with a previous myocardial infarction and recurrent, hemodynamically tolerated VT. A mean of 3.9±2.7 VTs were induced per patient (range, 1 to 10). The clinically documented arrhythmia was successfully ablated in 30 of 35 patients (86%), and on follow-up electrophysiological testing, 11 patients had no inducible VT and were discharged without other therapy. Nineteen patients had inducible “nonclinical” arrhythmias on follow-up testing, and the majority underwent cardiac defibrillator implantation. Freedom from recurrent arrhythmias, including sudden death, was 91% in patients without inducible VT and 53% in patients with persistently inducible “nonclinical” arrhythmias (
P
<.05; mean follow-up, 17±12 and 12±11 months, respectively).

Conclusions
In patients with well-tolerated VT, RF catheter ablation may be useful as a primary cure if no other ventricular arrhythmias are inducible on follow-up testing. Ablation of all hemodynamically tolerated arrhythmias should be attempted in patients with multiple inducible VT morphologies because of the high rate of recurrence of unablated VTs in these patients.
Evaluation of the Specificity of Morphological Electrocardiographic Criteria for the Differential Diagnosis of Wide QRS Complex Tachycardia in Patients With Intraventricular Conduction Defects
Authors: Alberca Teresa , Almendral Jesús , Sanz Petra , Almazan Aureliano , Cantalapiedra Jose Luis , Delcán Juan Luis
Published: June 2012

Background
Although several ECG criteria have been described for the differential diagnosis of tachycardias with a wide QRS complex, their applicability in patients with preexisting intraventricular conduction defects (IVCDs) has been questioned. The specificity of previously described criteria in this context is unknown.

Methods and Results
We analyzed prospectively the specificity of the QRS morphological criteria previously described in ECGs during sinus rhythm of 232 patients with IVCD. Only 5 of 12 analyzed criteria had a specificity ≥0.90 among our patients: (1) a triphasic configuration (Rsr′or Rr′) QRS complex in V
1
in the presence of a right bundle-branch block morphology (BBBM); (2) a QS, QR, or R QRS pattern in V
6
in the presence of a right BBBM; (3) any Q in V
6
in the presence of a left BBBM; (4) a concordant pattern in all precordial leads; and (5) the absence of an RS complex in all precordial leads (particularly useful for left BBBM). The following criteria—QRS duration >140 ms; a left axis with right BBBM, right superior axis with right BBBM, monophasic or biphasic R wave in V
1
with right BBBM, and a relation R/S <1 with right BBBM; an R >30 ms in lead V
1
or V
2
with left BBBM, >60 ms from QRS onset to S nadir with left BBBM, a notched downstroke S wave with left BBBM, and an R-to-S interval >100 ms in one precordial lead—had a specificity of 0.43, 0.54, 0.87, 0.80, 0.85, 0.78, 0.66, 0.69, and 0.63 (0.84 in right BBBM), respectively.

Conclusions
Most of the previously described morphological criteria favoring ventricular tachycardia are present in a substantial percentage of patients with IVCD during sinus rhythm. These findings suggest a limited applicability of these criteria in this subset of patients.
Association of Parvovirus B19 Genome in Children With Myocarditis and Cardiac Allograft Rejection
Authors: Schowengerdt Kenneth O. , Ni Jiyuan , Denfield Susan W. , Gajarski Robert J. , Bowles Neil E. , Rosenthal Geoffrey , Kearney Debra L. , Price Julia K. , Rogers Beverly B. , Schauer Gail M. , Chinnock Richard E. , Towbin Jeffrey A.
Published: June 2012

Background
Inflammatory diseases of the heart, including myocarditis and cardiac transplant rejection, are important causes of morbidity and mortality in children. Although viral infection may be suspected in either of these clinical conditions, the definitive etiology is often difficult to ascertain. Furthermore, the histology is identical for both disorders. Coxsackievirus has long been considered the most common cause of viral myocarditis; however, we previously demonstrated by polymerase chain reaction (PCR) analysis that many different, and sometimes unexpected, viruses may be responsible for myocarditis and cardiac rejection. In this study, we describe the association of parvovirus genome identified through PCR analysis of cardiac tissue in the clinical setting of myocarditis and cardiac allograft rejection.

Methods and Results
Myocardial tissue from endomyocardial biopsy, explant, or autopsy was analyzed for parvovirus B19 using primers designed to amplify a 699–base pair PCR product from the
VP1
gene region. Samples tested included those obtained from patients with suspected myocarditis (n=360) or transplant rejection (n=200) or control subjects (n=250). Parvoviral genome was identified through PCR in 9 patients (3 myocarditis; 6 transplant) and no control patients. Of the 3 patients with myocarditis, 1 presented with cardiac arrest leading to death, 1 developed dilated cardiomyopathy, and the other gradually improved. Four of the 6 transplant patients had evidence of significant rejection on the basis of endomyocardial biopsy histology. All transplant patients survived the infection.

Conclusions
Parvovirus is associated with myocarditis in a small percentage of children and may be a potential contributor to cardiac transplant rejection. PCR may provide a rapid and sensitive method of diagnosis.
Human Protein C Receptor Is Present Primarily on Endothelium of Large Blood Vessels
Authors: Laszik Zoltan , Mitro Alexander , Taylor Fletcher B. , Ferrell Gary , Esmon Charles T.
Published: June 2012

Background
The protein C anticoagulant pathway is critical to the control of hemostasis. Thrombomodulin and a newly identified receptor for protein C/activated protein C, EPCR, are both present on endothelium. EPCR augments activation of protein C by the thrombin-thrombomodulin complex.

Methods and Results
To gain a better understanding of the relationship between thrombomodulin and EPCR, we compared the cellular specificity and tissue distributions of these two receptors by using immunohistochemistry. EPCR expression was detected almost exclusively on endothelium in human and baboon tissues. In most organs, EPCR was expressed relatively intensely on the endothelium of all arteries and veins, most arterioles, and some postcapillary venules. EPCR staining was usually negative on capillary endothelial cells. In contrast, thrombomodulin was detected at high concentrations in both large vessels and capillary endothelium. Both thrombomodulin and EPCR were expressed poorly on brain capillaries. The liver sinusoids were the only capillaries in which EPCR was expressed at moderate levels and thrombomodulin was low. EPCR and thrombomodulin were both expressed on the endothelium of vasa recta in the renal medulla, the lymph node subcapsular and medullary sinuses, and some capillaries within the adrenal gland. Even in these organs the majority of capillaries were EPCR negative or stained weakly.

Conclusions
These studies suggest that EPCR may be important in enhancing protein C activation on large vessels. The presence of high levels of EPCR on arterial vessels may help explain why partial protein C deficiency is a weak risk factor for arterial thrombosis.
Etomoxir Improves Left Ventricular Performance of Pressure-Overloaded Rat Heart
Authors: Turcani Marian , Rupp Heinz
Published: June 2012

Background
Numerous studies have demonstrated diverse abnormalities in subcellular structures of pressure-overloaded hypertrophied and failing heart. Long-term administration of etomoxir, a carnitine palmitoyltransferase-1 inhibitor, partially normalized the proportion of myosin isozyme V
1
and number of active Ca
2+
pumps in hypertrophied rat myocardium.

Methods and Results
To test the hypothesis that long-term etomoxir treatment improves the performance of hypertrophied ventricle, sham-operated rats and rats with ascending aorta constriction were treated with racemic etomoxir (15 mg/kg per day) for 12 weeks. Left ventricular geometry, dynamics of isovolumic contractions, as well as myosin isozymes as marker of etomoxir-induced phenotype changes were assessed. Etomoxir stimulated (
P
<.05) slight hypertrophic growth in right and left ventricles of sham-operated rats as well as in right ventricles but not in overloaded left ventricles of rats with aortic constriction. In all treated rats, etomoxir increased (
P
<.05) maximal developed pressure, left ventricular pressure-volume area, and ±dP/dt
max
. Enhanced values (
P
<.05) of derived indexes of myocardial performance (normalized stress-length area, maximal rate of wall stress rise, and decline) indicated that myocardial changes were responsible for the improved performance. The etomoxir treatment increased selectively (
P
<.05) the proportion of myosin V
1
in pressure-overloaded left ventricles.

Conclusions
The long-term treatment with etomoxir improved functional capacity of pressure-overloaded left ventricle, which can be attributed to an enhanced myocardial performance. Chronic carnitine palmitoyltransferase-1 inhibition may thus represent a candidate approach for developing novel agents that are useful in the prevention of undesirable consequences of pressure overload–induced cardiac hypertrophy.
Direct Measurement of Three-dimensionally Reconstructed Flow Convergence Surface Area and Regurgitant Flow in Aortic Regurgitation
Authors: Shiota Takahiro , Jones Michael , Delabays Alain , Li Xiaokui , Yamada Izumi , Ishii Masahiro , Acar Philippe , Holcomb Scott , Pandian Natesa G. , Sahn David J.
Published: June 2012

Background
Evaluation of flow convergence (FC) with two-dimensional (2D) imaging systems may not be sufficiently accurate to characterize these often asymmetric, complex phenomena. The aim of this study was to validate a three-dimensional (3D) method for determining the severity of aortic regurgitation (AR) in an experimental animal model.

Methods and Results
In six sheep with surgically induced chronic AR, 20 hemodynamically different states were studied. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flow meters. Video composite data of color Doppler flow mapping images were transferred into a TomTec computer after computer-controlled 180° rotational acquisition. Direct measurement of the 3D reconstructed FC surface areas as well as measurements of FC areas estimated with 2D methods with hemispherical and hemielliptical assumptions were performed, and values were multiplied by the aliasing velocity to obtain peak regurgitant flow rates. There was better agreement between 3D and electromagnetically derived flow rates than there was between the 2D and the reference values (
r
=.94,
y
=1.0
x−
0.16, difference=0.02 L/min for the 3D method;
r
=.80,
y
=1.6
x
−0.3, difference=1.2 L/min for the 2D hemispherical method;
r
=.75,
y
=0.90
x
+0.2, difference=−0.20 L/min for the 2D hemielliptical method).

Conclusions
Without any geometrical assumption, the 3D method provided better delineation of the FC zones and direct measurements of FC surface areas, permitting more accurate quantification of the severity of AR than the 2D methods.