bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors and Sequelae of Distal Embolization During Saphenous Vein Graft Intervention From the CAVEAT-II Trial
Authors: Lefkovits Jeffrey , Holmes David R. , Califf Robert M. , Safian Robert D. , Pieper Karen , Keeler Gordon , Topol Eric J. , Investigators for the CAVEAT-II
Published: June 2012

Background
The purpose of this study was to identify the predictors and sequelae of distal embolization from a multicenter, randomized trial of saphenous vein graft intervention. The CAVEAT-II trial demonstrated that saphenous vein graft directional coronary atherectomy (DCA) was associated with greater angiographic success and less need for repeat intervention compared with percutaneous transluminal coronary angioplasty (PTCA) but at the cost of more acute complications—notably distal embolization.

Methods and Results
In CAVEAT-II, 305 patients were randomly assigned to DCA (149 patients) or PTCA (156 patients) for lesions with >60% diameter stenosis in vein grafts ≥3 mm in diameter. Distal embolization occurred in 20 patients (13.4%) assigned to DCA and 8 patients (5.1%) assigned to PTCA (
P
=.011). Independent predictors of distal embolization were use of DCA (71% in distal embolization patients versus 47% in patients without distal embolization,
P
=.011) and presence of thrombus (39% in distal embolization patients versus 14% in patients without distal embolization,
P
<.00). In-hospital adverse events were more frequent after distal embolization: 71% versus 20%, odds ratio plus (95% confidence intervals) 9.87 (4.65, 20.94). At 12-month follow-up, adverse event rates were also higher in patients with distal embolization (odds ratio, 3.05 [1.95, 4.76]).

Conclusions
In this first prospective multicenter trial of saphenous vein graft intervention, distal embolization was more common after DCA than PTCA and in lesions containing thrombus. It also was associated with worse in-hospital and 12-month outcomes. The risk and sequelae of distal embolization should be considered when choosing a treatment strategy for vein graft disease.
Quantitative Morphometric Analysis of Progressive Infundibular Obstruction in Tetralogy of Fallot
Authors: Geva Tal , Ayres Nancy A. , Pac Feyza A. , Pignatelli Ricardo
Published: June 2012

Background
The morphological hallmark of tetralogy of Fallot is controversial, with much disagreement as to whether the subpulmonary infundibulum in this lesion is hypoplastic. In addition, few quantitative data are available regarding the morphometry of the subpulmonary infundibulum, what anatomic characteristics are acquired in the postnatal period, and at what rate they progress. We also sought to determine whether echocardiographic morphometric analysis of the infundibulum can predict clinical course in infants with tetralogy of Fallot.

Methods and Results
Twenty-one infants with tetralogy of Fallot (median age at initial study, 1.6 months) were prospectively followed with serial echocardiograms until the time of first surgical intervention (median age at surgery, 10 months). Selected video still frames were digitized off-line with a computerized system. Compared with age-matched normal control infants (n=37), the following indexed infundibular dimensions in patients with tetralogy of Fallot were significantly smaller: length (1.86±0.54 versus 2.7±0.56 cm/BSA
0.5
,
P
<.0001), cross-sectional area (1.6±0.49 versus 4.7±1.3 cm
2
/BSA,
P
<.0001), and volume (1.24±0.62 versus 7.2±3 mL/BSA
1.5
,
P
<.0001). The following measurements were increased in tetralogy patients: infundibular septal thickness (0.83±0.21 versus 0.54±0.06 cm/BSA
0.5
,
P
=.0002) and infundibular free-wall thickness (0.62±0.13 versus 0.49±0.06 cm/BSA
0.5
,
P
=.006). The angle between infundibular septum and ventricular septum had a greater degree of anterosuperior deviation in tetralogy patients, resulting in a larger infundibuloventricular septal angle (77±8.2° versus 31±6.5°,
P
<.0001). During follow-up, infundibular volume in tetralogy patients decreased from 1.24±0.62 to 0.81±0.47 mL/BSA
1.5
(
P
=.002), correlating with infundibular septal thickness (
r
=−.63,
P
<.003). The mean rate of decrease of indexed infundibular volume was 0.1±0.13 mL · BSA
−1.5
· mo
−1
. Correlation analysis revealed a nonlinear correlation between the degree of infundibular septal malalignment and indexed infundibular volume (
r
=.93,
P
<.0001). Tetralogy patients who required early surgical intervention (4.8±0.9 versus 10.7±1.7 months,
P
<.0001) had a smaller infundibulum at presentation (0.92±0.35 versus 1.41±0.67 mL/BSA
1.5
,
P
=.04) and an accelerated rate of infundibular narrowing (0.17±0.18 versus 0.06±0.08 mL · BSA
−1.5
· mo
−1
,
P
=.04).

Conclusions
Compared with normal infants, the subpulmonary infundibulum in tetralogy of Fallot is characterized by a smaller volume, shorter and thicker infundibular septum, and anterosuperior deviation of the infundibular septum. Infundibular obstruction in tetralogy patients is progressive, with an average rate of decrease in indexed infundibular volume of 0.1±0.13 mL · BSA
−1.5
· mo
−1
. Infants who are likely to require early therapeutic intervention may be identified on their initial echocardiogram as having an infundibular volume of <0.9 to 1.0 mL/BSA
1.5
.
Chronic Hypoxia Differentially Regulates α
1
-Adrenergic Receptor Subtype mRNAs and Inhibits α
1
-Adrenergic Receptor–Stimulated Cardiac Hypertrophy and Signaling
Authors: Li Hong-Tai , Long Carlin S. , Rokosh D. Gregg , Honbo Norman Y. , Karliner Joel S.
Published: June 2012

Background
After myocardial ischemia and/or infarction, surviving cardiac myocytes in and around the injured zone develop hypertrophy to compensate for the loss of contractile units due to myocyte injury and death. One of the factors that may be involved in the development of hypertrophy after ischemic injury is norepinephrine (NE), an agent that induces hypertrophy of cardiac myocytes through the α
1
-adrenergic receptor (AR). It is not known, however, whether hypoxia, a major component of ischemia, has any direct effect on NE-stimulated hypertrophy. Therefore, we sought to determine whether chronic hypoxia could alter NE-stimulated hypertrophy and if so, whether this alteration was related to α
1
-AR–mediated signaling and α
1
-AR changes at both the protein and mRNA levels.

Methods and Results
We developed a model of chronic hypoxia in cultured neonatal rat cardiac myocytes in which myocytes were exposed to 1% oxygen for 72 hours. Initially, we observed that chronic hypoxia inhibited NE-stimulated hypertrophy, as reflected by decreases in both new protein synthesis and total protein content during chronic hypoxia. Then we found that chronic hypoxia also inhibited α
1
-AR–transduced phosphatidylinositol hydrolysis, as indicated by a reduction in α
1
-AR–stimulated inositol phosphate production in hypoxic cells. These observations suggested that the inhibition of NE-stimulated hypertrophy seen during chronic hypoxia was due to impairment of α
1
-AR–mediated signaling and could result from changes in α
1
-AR numbers and/or subtype distribution. To address this issue, we determined α
1
-AR density and subtype distribution by radioligand binding and α
1
-AR subtype mRNAs, including α
1A/D
-, α
1B
-, and α
1C
-ARs, by RNase protection assays. We found that chronic hypoxia differentially regulated both the pharmacologically defined α
1
-AR subtypes and the mRNAs for the α
1
-AR subtypes. Thus, hypoxia for 72 hours coordinately downregulated both the pharmacologically defined α
1A
-AR density and the α
1C
-AR mRNA level. During normoxia, NE increased the pharmacologically defined α
1A
-AR density and the α
1C
-AR mRNA level, but hypoxia for 72 hours prevented these NE-mediated changes.

Conclusions
Chronic hypoxia (1) inhibits α
1
-AR–mediated hypertrophy of cardiac myocytes and α
1
-AR–transduced phosphatidylinositol hydrolysis and (2) downregulates both the pharmacologically defined α
1A
-AR density and the α
1C
-AR mRNA level.
Hepatic Venous Blood and the Development of Pulmonary Arteriovenous Malformations in Congenital Heart Disease
Authors: Srivastava Deepak , Preminger Tamar , Lock James E. , Mandell Valerie , Keane John F. , Mayer John E. , Kozakewich Harry , Spevak Philip J.
Published: June 2012

Background
Pulmonary arteriovenous malformations (PAVMs) are a known complication after some types of cavopulmonary anastomoses (CVPAs). Their cause is unknown, but they may be related to the absence of pulsatile flow or the presence or absence of circulating factors. These PAVMs are diffuse and are presumed to be progressive and irreversible.

Methods and Results
All patients with congenital heart disease (CHD) seen at Children’s Hospital, Boston, Mass, between 1970 and 1993 were reviewed. We report on the 10 patients with CHD who were found to have developed PAVMs, as diagnosed by cardiac catheterization. Diagnoses included heterotaxy syndrome/polysplenia, with interrupted inferior vena cava and hepatic veins draining to the right atrium (n=6); heterotaxy/asplenia (n=1); corrected transposition with pulmonary stenosis (n=1); and biliary atresia and associated CHD (n=2). PAVMs were diagnosed 0.1 to 7.0 years (median, 3.5 years) after creation of a CVPA that resulted in exclusion of hepatic venous flow from one or both lungs in 8 of the 10 patients; the remaining 2 patients had normal drainage of hepatic veins to the lungs but had biliary atresia. In all, the common anatomic feature was the exclusion of normal hepatic venous return from the affected pulmonary arterial circulation. All patients with interrupted inferior vena cava, azygous continuation to the superior vena cava, and hepatic veins draining to the right atrium (polysplenia syndrome) were reviewed to determine the incidence of PAVMs in those with CVPA (ie, hepatic venous flow excluded from the pulmonary arteries) and without CVPA. Six of 28 (21%) of those with versus 1 of 56 (1.8%) of those without CVPA developed PAVMs (
P
=.004). The 1 patient without CVPA who had PAVMs also had biliary atresia. Among patients with CVPA, the probability of developing PAVMs was 15% and 28% at 3 and 5 years, respectively, after CVPA. The histological and angiographic appearances of PAVMs after CVPA are similar to those seen in PAVMs associated with hepatic cirrhosis.

Conclusions
We postulate that PAVMs after CVPA are related to the diversion of normal hepatic venous flow from the pulmonary circulation. In this sense, these PAVMs may be analogous to those associated with liver disease, which have been found to resolve after liver transplantation. Redirection of hepatic flow to the pulmonary bed in some patients with CHD and PAVMs may lead to reversibility of the PAVMs.
Linear Ablation of the Isthmus Between the Inferior Vena Cava and Tricuspid Annulus for the Treatment of Atrial Flutter
Authors: Tabuchi Toshifumi , Okumura Ken , Matsunaga Toshiro , Tsunoda Ryusuke , Jougasaki Michihisa , Yasue Hirofumi
Published: June 2012

Background
The isthmus between the inferior vena cava and the tricuspid annulus has been shown to be involved in the reentry circuit of common atrial flutter. The effects of radiofrequency catheter ablation of this isthmus were examined in the canine model of atrial flutter due to reentry around the tricuspid annulus.

Methods and Results
A model of atrial flutter was prepared in 11 of 14 dogs by creating intercaval and connected transverse lesions (Y-shaped lesion). Bipolar electrodes were attached at 24 atrial sites, and computer-assisted mapping was performed. Stable atrial flutter with a cycle length of 133±11 ms was repeatedly induced by rapid atrial pacing in all dogs, and atrial mapping revealed reentry around the tricuspid annulus including the isthmus. In 6 dogs, the isthmus was ligated during atrial flutter (mechanical ablation). In the other 5 dogs, a 7F large-tip electrode catheter was placed at the isthmus under a fluoroscopic control. Radiofrequency energy (25 W for 30 s) was delivered to three sequential sites from the tricuspid annulus to the inferior vena cava to ablate the isthmus linearly. Atrial flutter was terminated in all dogs after mechanical and radiofrequency ablation of the isthmus and was not induced again. Atrial pacing from the posterior left atrium during sinus rhythm demonstrated intra-atrial conduction block at the isthmus after ablation. Pathological examination of the isthmus showed transmural myocardial damage.

Conclusions
Linear radiofrequency ablation of the isthmus can induce intra-atrial conduction block and is effective as a curative therapy for atrial flutter when the reentry circuit involves the isthmus.
Visualization of Thrombi in Pulmonary Arteries With Radiolabeled, Enzymatically Inactivated Tissue-Type Plasminogen Activator
Authors: Bruyn Van H. De , Bergmann Steven R. , Keyt Bruce A. , Sobel Burton E.
Published: June 2012

Background
Despite the high frequency of pulmonary thromboembolism and its significant morbidity and mortality, diagnosis remains suboptimal. We have been developing a method for prompt detection with the use of radiolabeled, inactivated tissue-type plasminogen activator (TPA) and performed the present study to determine whether its use permits rapid scintigraphic visualization of pulmonary thrombi in vivo.

Methods and Results
The thrombolytic, but not fibrin-binding, property of TPA was inactivated with a tripeptide chloromethyl ketone (YPACK) that had already been iodinated with
123
I to radiolabel the TPA. Pulmonary arterial thrombosis was induced in nine dogs with the use of guide wires modified to provide thrombogenic tips.
123
I-YPACK-TPA (1.1 to 7.8 mCi, 0.5 to 7.8 mg) was infused for 5 minutes into either the systemic or the pulmonary circulation. Clearance of radioactivity from the blood was rapid and indistinguishable from that of unlabeled, thrombolytically active TPA, with only 6.7±1.0% (mean±SEM) of peak radioactivity remaining after 60 minutes and minimal release of labeled fragments from the liver during this interval. Thrombi were visualized with single photon emission computed tomography and/or planar imaging 40 to 120 minutes after infusion of tracer in all seven animals given at least 3.7 mCi of
123
I-YPACK-TPA. Ratios of radioactivity in thrombus (wet mass, 610±64 mg) to blood were high (14±3:1).

Conclusions
The use of radiolabeled TPA in which thrombolytic activity is inactivated permits prompt scintigraphic detection of thrombi in pulmonary arteries in vivo.
Valvular and Systemic Arterial Hemodynamics in Aortic Valve Stenosis
Authors: Laskey Warren K. , Kussmaul William G. , Noordergraaf Abraham
Published: June 2012

Background
Assessment of the severity of a stenotic aortic valve has been confounded by reports of flow dependence of stenosis severity. We hypothesized that the pressure gradient at the stenotic aortic valve would be dependent on the characteristics of the arterial circulation. Therefore, clinically useful measures of the severity of aortic valve stenosis may have to take this dependence into account.

Methods and Results
We developed an analog model of the systemic arterial circulation in the presence of a stenotic aortic valve. The model clearly describes the dependence of stenosis severity (described by coefficients A and B) on the resistive and capacitive properties of the arterial system. We used high-fidelity pressure recordings obtained at the time of diagnostic cardiac catheterizations and found that a highly significant relation between the measured mean transvalvular gradient and that predicted by the model was demonstrated both at rest (
r
2
=.90) and with exercise (
r
2
=.80). Furthermore, the relative constancy of stenosis coefficients A and B was validated.

Conclusions
Transvalvular hemodynamics in patients with aortic valve stenosis are dependent on the properties of the arterial system. The current model describes such behavior, correctly predicts the transvalvular gradient from model parameters, and may be useful in the assessment of stenosis severity under various clinical and physiological conditions.
Chronic Congestive Heart Failure Is Associated With a Phenotypic Shift of Intramyocardial Endothelial Cells
Authors: Marijianowski Monique M.H. , van Laar Marjolein , Bras Johannes , Becker Anton E.
Published: June 2012

Background
There is evidence that patients with chronic congestive heart failure have endothelial cell–related abnormalities of the peripheral circulation and the coronary microvasculature. For that reason, we have studied the phenotypic expression of endothelial cells in hearts of patients with congestive heart failure.

Methods and Results
We studied cardiac explants (n=19) and autopsy hearts (n=5) of patients with chronic congestive heart failure caused by either a dilated cardiomyopathy (n=12) or ischemic heart disease (n=12) and compared them with normal hearts (n=12). The antigenic expression obtained with several endothelial cell markers (factor VIII–related antigen, EN-4, Ulex europaeus agglutinin–1 (UEA-1), PAL-E, endoglin, and endothelin) and adhesion molecules (intercellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], or E-selectin) was compared by use of immunohistochemical techniques. On the basis of the initial findings, the number of PAL-E– and EN-4–positive vessels was counted. The incidence of PAL-E–positive vessels per area was quantified and related to the percentage of heart muscle cells and the total number of vessels per area. In control hearts, endothelial cells rarely were positive for PAL-E. In hearts of patients with ischemic cardiomyopathies, there was distinct staining with this marker. Hearts of patients with dilated cardiomyopathies showed a marked increase in the number of PAL-E–positive endothelial cells. Vessels with a muscular media were PAL-E–negative. Two-sample analysis revealed a statistically significant difference between hearts with dilated cardiomyopathies and ischemic cardiomyopathies (
P
<.01), between hearts with dilated cardiomyopathies and control hearts (
P
<.01), and between hearts with ischemic cardiomyopathies and control hearts (
P
<.01). Endoglin and ICAM were positive but nondiscriminating. Endothelin, VCAM, and E-selectin were negative.

Conclusions
A phenotypic shift in endothelial antigen expression of the coronary microvasculature occurs in both ischemic hearts and hearts with dilated cardiomyopathies, as revealed by PAL-E, compared with control hearts. The change may relate to compensatory mechanisms in long-standing chronic heart failure.
Insulin-Stimulated Glucose Transport Inhibits Ca
2+
Influx and Contraction in Vascular Smooth Muscle
Authors: Kahn Andrew M. , Lichtenberg Richard A. , Allen Julius C. , Seidel Charles L. , Song Tom
Published: June 2012

Background
Insulin attenuates serotonin-induced Ca
2+
influx, the intracellular Ca
2+
transient, and contraction of cultured vascular smooth muscle cells from dog femoral artery. These studies were designed to test whether insulin-induced glucose transport was an early event leading to the inhibitory effects of insulin on Ca
2+
influx, intracellular Ca
2+
concentration, and contraction in these cells.

Methods and Results
Insulin 1 nmol/L stimulated the 30-minute uptake of [
3
H]2-deoxyglucose in these cells via a phloridzin-inhibitable mechanism. Contraction of individual cells was measured by photomicroscopy, intracellular Ca
2+
concentration was monitored by measuring fura 2 fluorescence by use of Ca
2+
-sensitive excitation wavelengths, and Ca
2+
influx was estimated by the rate of Mn
2+
quenching of intracellular fura 2 fluorescence when excited at a Ca
2+
-insensitive wavelength. In the presence of 5 mmol/L glucose, preincubation of cells for 30 minutes with 1 nmol/L insulin inhibited 10
−5
mol/L serotonin-induced contraction of individual cells by 62% (
P
<.01) and decreased the serotonin-stimulated component of Mn
2+
influx by 78% (
P
<.05). Removing glucose from the preincubation medium or adding 1 mmol/L phloridzin completely eliminated these effects of insulin. Insulin lowered the serotonin-induced intracellular Ca
2+
peak by 37% (
P
<.05), and phloridzin blocked this effect of insulin. When glucose uptake was increased to the insulin-stimulated level by preincubation of the cells for 30 minutes with 25 mmol/L glucose in the absence of insulin, serotonin failed to stimulate Mn
2+
influx, the serotonin-induced Ca
2+
peak was decreased by 46% (
P
<.05), serotonin-induced contraction was inhibited by 60% (
P
<.01), and addition of insulin did not further inhibit contraction.

Conclusions
Since the effects of insulin on serotonin-stimulated Ca
2+
transport, intracellular Ca
2+
concentration, and contraction were dependent on glucose transport and were duplicated when glucose transport was stimulated by high extracellular glucose concentration rather than insulin per se, it is concluded that insulin-stimulated glucose transport is an early event that leads to decreased Ca
2+
influx and contraction in vascular smooth muscle.
Therapy With Immunoglobulin Suppresses Myocarditis in a Murine Coxsackievirus B3 Model
Authors: Takada Hitoshi , Kishimoto Chiharu , Hiraoka Yuji
Published: June 2012

Background
The treatment of some inflammatory diseases (eg, Kawasaki disease) with immunoglobulin has been demonstrated to be effective. Accordingly, to elucidate the mechanism underlying such actions of immunoglobulin, we examined its effects on murine coxsackievirus B3 (CB3) myocarditis.

Methods and Results
An in vitro study showed dose-dependent suppression of CB3 by immunoglobulin. Immunoglobulin 1 g · kg
−1
· d
−1
IP was administered to CB3-infected C3H/He mice daily for 2 weeks, beginning simultaneously with virus inoculation in experiment 1 and on day 14 after virus inoculation in experiment 2. In both experiments, survival was higher in treated than in control mice; at the time of death, inflammatory cell infiltration and the severity of necrosis and calcification also were reduced. Notably, in experiment 1, immunoglobulin administration completely suppressed the development of myocarditis. Serum-neutralizing antibody titers in the treated mice were significantly higher than those in untreated mice in experiment 1 but not in experiment 2. The circulating antibodies of the treated mice were primarily of exogenous origin in experiment 1 and of exogenous and endogenous origins in experiment 2. The analysis of splenic lymphocyte subsets revealed a marked decrease of the B cell population in the treated mice.

Conclusions
Immunoglobulin therapy completely suppressed acute CB3 myocarditis by transferring the neutralizing antibody into the host in the acute viremic stage and induced an anti-inflammatory effect in the subsequent aviremic stage; the reduction of the splenic B-cell population may be closely associated with an anti-inflammatory effect.
Transthoracic Defibrillation of Swine With Monophasic and Biphasic Waveforms
Authors: Gliner Bradford E. , Lyster Thomas E. , Dillion Stephen M. , Bardy Gust H.
Published: June 2012

Background
Biphasic waveforms have had a favorable impact on internal defibrillation but have seen minimal use in transthoracic defibrillation systems. The purpose of this study was to compare monophasic and biphasic waveforms for transthoracic defibrillation in swine.

Methods and Results
Three interrelated studies were performed in 19 swine to establish the relative transthoracic defibrillation efficacy of biphasic shock waveforms. In study 1, we measured voltage (V
50
) and energy (E
50
) strength-duration curves for monophasic and biphasic truncated exponential waveforms. We then independently examined the effects of phase duration and tilt on biphasic waveform defibrillation with a total waveform duration from study 1 that provided the minimum V
50
(study 2) and the minimum E
50
(study 3). At each pulse duration tested in study 1, biphasic waveforms defibrillated with significantly less voltage and energy than monophasic waveforms. At a duration of 12 ms, there was a voltage minimum for biphasic waveform defibrillation. At this duration, V
50
was 1378±505 V for the biphasic waveform compared with 2185±361 V for the monophasic waveform,
P
=.01. For both monophasic and biphasic waveforms, E
50
increased with pulse duration. With a total pulse duration of 12 ms, E
50
was 169±101 J for the biphasic waveform compared with 414±114 J for the monophasic waveform,
P
=.003. In study 2, optimization of phase duration and total tilt reduced the defibrillation requirements of the 12-ms “minimum voltage” biphasic waveform to 1284±187 V and 129±36 J. In study 3, the 8-ms “minimum energy” biphasic waveform had an E
50
of 115±35 J that was 11% less than the 12-ms biphasic waveform,
P
=.11; however, voltage requirements of 1476±239 V were 15% higher,
P
=.005.

Conclusions
This study demonstrates the superiority of truncated biphasic waveforms over truncated monophasic waveforms for transthoracic defibrillation of swine. Biphasic waveforms should prove as advantageous at reducing voltage and energy requirements for transthoracic defibrillation as they have for internal defibrillation.
Angiotensin-I Converting Enzyme Genotypes and Left Ventricular Hypertrophy in Patients With Hypertrophic Cardiomyopathy
Authors: Lechin Marcel , Quiñones Miguel A. , Omran Ahmad , Hill Rita , Yu Qun-Tao , Rakowski Harry , Wigle Douglas , Liew C.C. , Sole Michael , Roberts Robert , Marian Ali J.
Published: June 2012

Background
The variability of the phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) indicates a potential role for additional modifying genes. Variants of angiotensin-I converting enzyme (ACE) gene have been implicated in cardiac hypertrophy. To assess whether ACE genotypes influence the phenotypic expression of hypertrophy, we determined the left ventricular mass index (LVMI) and extent of hypertrophy in 183 patients with HCM.

Methods and Results
LVMI was derived by the area-length method using two-dimensional echocardiograms. Extent of LVH was determined by a point score method (1 to 10 points). DNA was extracted from blood, and ACE genotyping was performed by polymerase chain reaction (PCR) with an established protocol. Amplification of DNA in the region of polymorphism by PCR of alleles I and D showed 490- and 190-bp products, respectively. ACE genotypes DD, ID, and II were present in 60, 90, and 33 patients with HCM, respectively. In genetically independent patients (n=108), the mean LVMI (g/m
2
) was 148±35.3 in those with DD (n=35) and 134.2±33.3 in those with ID and II (n=73) genotypes (
P
=.046). LVH score was 6.69±1.71 in patients with DD and 5.55±2.19 in those with ID and II genotypes (
P
=.004). Regression analysis showed that ACE genotypes accounted for 3.7% and 6.5% of the variability of LVMI and LVH score (
P
=.046 and
P
=.008, respectively). In 26 patients from a single family, LVMI and LVH score were also greater in patients with DD than in those with ID and II genotypes. ACE genotypes accounted for 14.7% and 10.4% of the variability of the LVMI and extent of hypertrophy, respectively.

Conclusions
ACE genotypes influence the phenotypic expression of hypertrophy in HCM.
Anatomically and Physiologically Based Reference Level for Measurement of Intracardiac Pressures
Authors: Courtois Michael , Fattal Peter G. , Kovács Sandor J. , Tiefenbrunn Alan J. , Ludbrook Philip A.
Published: June 2012

Background
Many reference levels have been proposed for the measurement of intracardiac pressures, but none have met with universal acceptance. In the first part of our study, we evaluated 10 cardiologists’ understanding of how hydrostatic pressure influences intracardiac pressures as measured with fluid-filled catheters. In the second part, we proposed and validated a new zero level (H): the uppermost blood level in the left ventricular (LV) chamber relative to the anterior chest wall for a patient in the supine position. A comparison was made of LV minimum diastolic pressure measured by reference to H versus measurements made with the zero level at midchest.

Methods and Results
Using two-dimensional echocardiography, we determined H in the LVs of seven normal patients (five male, two female; age, 49±9 years) undergoing routine cardiac catheterization. H was determined from a left parasternal short-axis view and calculated as the average distance between end diastole and end systole of the endocardium of the uppermost segment of the LV anterior wall below the fourth or fifth intercostal space of the left sternal border on the anterior surface of the chest wall, with the patient in the supine position. A micromanometer/fluid-filled lumen catheter was then positioned in the LV, and we compared the micromanometer LV minimum pressure (LVP
min
) obtained when the reference fluid-filled transducer was aligned at midchest with the LVP
min
obtained when the reference fluid-filled transducer was aligned at H. LVP
min
referenced to a midchest fluid-filled external transducer was measured as 5.1±1.6 mm Hg (range, 2.4 to 7.2 mm Hg) versus −0.6±0.6 mm Hg (range, −1.6 to 0.4 mm Hg) when referenced to H (
P
<.001). A significant linear relation was found to exist between patient anterior-posterior chest diameter and the magnitude of hydrostatic pressure influences related to pressure referenced at midchest (
r
=.88;
P
<.01).

Conclusions
External fluid-filled transducers should be used with the goal of removing hydrostatic pressure and other influences so that the presence of subatmospheric pressure during diastole in any of the cardiac chambers is accurately measured. To achieve this goal, intracardiac pressure should be referenced to an external fluid-filled transducer aligned with the uppermost blood level in the chamber in which pressure is to be measured. The current practice of referencing the zero level of LV diastolic pressure to an external fluid-filled transducer positioned at the midchest level results in systematic overestimation due to hydrostatic effects and produces physiologically significant error in the measurement of diastolic intracardiac pressure.
Limb Vasoconstriction After Successful Angioplasty of the Left Anterior Descending Coronary Artery
Authors: Indolfi Ciro , Piscione Federico , Ceravolo Roberto , Maione AntonGiulio , Focaccio Amelia , Rao Maria Assunta , Esposito Giovanni , Condorelli Mario , Chiariello Massimo
Published: June 2012

Background
Coronary vasoconstriction has been described after uncomplicated percutaneous transluminal coronary angioplasty (PTCA). However, it is still unknown whether this phenomenon is limited to coronary circulation. The present study was planned to assess the effects of a successful PTCA on forearm blood flow (FBF) and resistance. The role of α-adrenoceptors and calcium antagonist agents on PTCA-induced limb blood flow changes was also investigated.

Methods and Results
We prospectively studied 37 patients scheduled for elective single PTCA of the left anterior descending coronary artery. All patients had evidence of exercise-induced myocardial ischemia. All vasoactive drugs were withdrawn for at least 48 hours before the study. FBF was measured by calibrated venous occlusion plethysmography. A significant reduction of FBF was observed at 1, 5, and 15 minutes after PTCA (from 3.7±1.2 to 2.7±1.5, 3.0±1.6, and 2.9±1.9 mL/100 mL tissue per minute, respectively; all
P
<.05 versus baseline). Vascular forearm resistance also increased at 1, 5, and 15 minutes after PTCA (from 27±8 to 42±16, 37±10, and 43±19 U, respectively; all
P
<.05 versus baseline). Phentolamine (12 μg · kg
−1
· min
−1
, n=7) or verapamil (3.5 μg · kg
−1
· min
−1
, n=7) also was infused intra-arterially. PTCA-induced forearm vasoconstriction was completely abolished by pretreatment with regional infusion of phentolamine or verapamil.

Conclusions
After an uncomplicated PTCA of the left anterior descending coronary artery, a reduction in FBF and an increase in forearm vascular resistance were observed. This peripheral vasoconstrictive response was probably due to α-adrenergic stimulation and was abolished by intra-arterial infusion of calcium antagonist agents.
Pharmacological Evidence for the Persistent Activation of ATP-Sensitive K
+
Channels in Early Phase of Reperfusion and Its Protective Role Against Myocardial Stunning
Authors: Shigematsu Sakuji , Sato Toshiaki , Abe Takako , Saikawa Tetsunori , Sakata Toshiie , Arita Makoto
Published: June 2012

Background
The activation of cardiac ATP-sensitive potassium channels is reported to protect myocardium during ischemia. However, the behavior and role of this channel during reperfusion remain uncertain.

Methods and Results
Guinea pig right ventricular walls were studied by use of microelectrodes and a force transducer. Each preparation was perfused via the coronary artery at a constant flow rate and was stimulated at 3 Hz. In the first protocol, the preparation was subjected to 10 minutes of no-flow ischemia, which was followed by 60 minutes of reperfusion. Introduction of ischemia shortened the action potential duration (APD) to 58.7±3.1% of the preischemic values, in association with a decrease in the resting membrane potential (by 12±0.8 mV) and action potential amplitude (by 34.6±1.8 mV). On reperfusion, although the APD was restored, it remained shortened for up to approximately 30 minutes of reperfusion. In the presence of glibenclamide (10 μmol/L), the shortening of the APD during ischemia was significantly attenuated and the restoration of APD after reperfusion was significantly facilitated. When glibenclamide was applied from the onset of reperfusion, the persistent APD shortening was significantly suppressed. The developed tension decreased during ischemia and recovered after 60 minutes of reperfusion (up to 92.0±6.4% of preischemic values) in the untreated preparations. The application of glibenclamide that was started before ischemia or from the onset of reperfusion significantly suppressed the recovery of contractility (
P
<.05 versus untreated preparations). In the second series of experiments, 20 minutes of no-flow ischemia and 60 minutes of reperfusion were applied. This protocol produced a sustained contractile dysfunction after reperfusion (to 34.0±3.2% of preischemic values). In the presence of cromakalim (2 μmol/L), the APD shortening was enhanced during both ischemia and the early reperfusion period. Cromakalim significantly improved the contractile recovery (to 79.3±4.1% of preischemic values,
P
<.05 versus untreated preparations). The application of cromakalim that was started from the onset of reperfusion also improved the contractile recovery during this phase and this effect was associated with enhanced APD shortening. However, the cromakalim-treated preparations demonstrated a higher incidence of ventricular fibrillation during reperfusion.

Conclusions
Cardiac ATP-sensitive potassium channels are activated by ischemia, and a fraction of these channels remains activated during the early reperfusion phase. The resulting shortening of the APD prevents the heart from developing myocardial stunning.
Intra-arterial Beta Irradiation Prevents Neointimal Hyperplasia in a Hypercholesterolemic Rabbit Restenosis Model
Authors: Verin Vitali , Popowski Youri , Urban Philip , Belenger Jacques , Redard Mireille , Costa Manuel , Widmer Marie-Claude , Rouzaud Michel , Nouet Philippe , Grob Eugène , Schwager Michael , Kurtz John M. , Rutishauser Wilhelm
Published: June 2012

Background
Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems.

Methods and Results
Flexible 90-yttrium (
90
Y) coils inside a centering balloon were used to allow homogeneous intra-arterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245±93 cells/cm in control, 42±27 in 6 Gy, 72±107 in 12 Gy, and 2±2 in 18 Gy groups;
P
<.001) and in total neointimal cells (891±415 cells/cm in control, 79±43 in 6 Gy, 192±264 in 12 Gy and 22±13 in 18 Gy groups;
P
<.0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26±10% in the control group to 1±1.3% in the 18 Gy group (
P
<.0001), but lower doses had no significant effect.

Conclusions
Administration of intra-arterial beta irradiation with a
90
Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.
Effect of the Implantable Left Ventricular Assist Device on Neuroendocrine Activation in Heart Failure
Authors: James Karen B. , McCarthy Patrick M. , Thomas James D. , Vargo Rita , Hobbs Robert E. , Sapp Shelly , Bravo Emmanuel
Published: June 2012

Background
The HeartMate left ventricular assist device has been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement in their heart failure after HeartMate implantation, we studied the physiological effect of this device on the neurohormonal axis.

Methods and Results
In 13 patients awaiting transplant (mean cardiac index, 1.7±0.3 L · min
−1
· m
−2
) who underwent HeartMate implantation, venous atrial natriuretic peptide, epinephrine, norepinephrine, plasma renin activity, angiotensin, and arginine vasopressin were measured immediately before insertion and at explant/transplantation. Mean time to explant was 86±40 days. All patients were taken off inotropic medications within 1 month. Mean cardiac index on support before explant was 3.1±0.9 L · min
−1
· m
−2
. Plasma renin activity decreased from 57±56 ng · mL
−1
· h
−1
at baseline (before insertion) to 3±3 ng · mL
−1
· h
−1
at explant (mean percent change, 92%;
P
<.001). Angiotensin II level decreased from 237±398 U/L at baseline to 14±14 U/L at explant (mean percent change, 73%;
P
<.001). Plasma epinephrine level fell from 6800±1323 pg/mL at baseline to 46±46 pg/mL at explant (mean percent change, 86%;
P
<.001). Norepinephrine level decreased from 2953±1457 pg/mL at baseline to 518±290 pg/mL at explant (mean percent change, 79%;
P
<.001). Atrial natriuretic peptide fell from baseline values of 227±196 to 168±40 pg/mL at explant (mean percent change, −49%;
P
=.519); and arginine vasopressin level decreased from 6±6 pg/mL at baseline to 0.8±0.5 pg/mL (mean percent change, 69%;
P
=.002).

Conclusions
We provide data supporting that the neurohormonal axis markedly improves after HeartMate implantation, providing biochemical confirmation of the improvement in hemodynamic status.
Determinants of Length of Stay After Coronary Artery Bypass Graft Surgery
Authors: Lazar Harold L. , Fitzgerald Carmel , Gross Stacy , Heeren Tim , Aldea Gabriel S. , Shemin Richard J.
Published: June 2012

Background
Rising healthcare costs have prompted limitations in the length of stay (LOS) for patients undergoing coronary artery bypass graft surgery (CABG). Because not all patients are candidates for early discharge, in the present study our aim was to determine factors that prolong LOS.

Methods and Results
In 194 consecutive patients undergoing CABG procedures, LOS was >7 days in 37%. Stepwise multiple regression procedures and χ
2
testing were used to determine what factors prolonged LOS for >7 days. Preoperative factors that significantly (
P
<.05) prolonged LOS included repeat CABG, CABG plus valve surgery, congestive heart failure, preoperative coronary care unit stay, renal failure, and insulin-dependent diabetes mellitus. Patients with at least one risk factor had a significantly higher incidence of LOS of >7 days (47% versus 17%;
P
<.001). Significant (
P
<.05) postoperative factors prolonging LOS included arrhythmias, respiratory insufficiency, pneumonia, and wound infection. Of patients with at least one risk factor, 83% had LOS of >7 days (
P
<.001).

Conclusions
The presence of certain preoperative and postoperative risk factors can be predicted to prolong LOS after CABG surgery. This should be taken into consideration when defining reimbursement policies.
Clinical Study of the Effects of Latissimus Dorsi Muscle Flap Stimulation After Cardiomyoplasty
Authors: Hagège Albert Alain , Desnos Michel , Fernandez Francisco , Besse Bruno , Mirochnik Nikolaı̈ , Castaldo Monica , Chachques Juan Carlos , Carpentier Alain , Guérot Claude
Published: June 2012

Background
Beneficial hemodynamic effects after dynamic cardiomyoplasty have been inconsistently demonstrated, and the effects seen may be due to the wrap itself, to flap stimulation, or both. The aim of this study was to determine whether flap stimulation per se acts as a systolic active process after cardiomyoplasty.

Methods and Results
Catheterizations were performed in 13 patients 14.4±7 months after cardiomyoplasty. New York Heart Association functional class decreased from 3.3 to 2.1 after the procedure (
P
=.0005). Hemodynamic evaluations were first performed with the stimulator on in the 2:1 mode and then after the stimulator had been off for at least 24 hours. Left ventricular (LV) ejection fraction increased from 25.1±6% before surgery to 28.2±6.7% with the stimulator on after cardiomyoplasty (
P
=.04). When stimulation was stopped, there was no change (
P
>.05) in indexes of systolic or diastolic LV function (peak systolic LV pressure, LV ejection fraction, peak positive dP/dt, peak negative dP/dt, or τ). Pulmonary capillary wedge pressure and cardiac index were unchanged when stimulated and nonstimulated settings were compared (
P
>.05). However, a remarkable heterogeneity of individual responses was observed. Ejection fraction and cardiac index decreased with the stimulator off in 3 patients, but peak positive dP/dt decreased in 6 patients; diastolic function deteriorated in 2 patients, but a slight improvement was noted in 3 patients. Cardiothoracic ratio, echocardiographic LV end-diastolic dimension, and fractional shortening remained unchanged between immediate (<1 month) and long-term (36.7±25.9 months) postoperative evaluations.

Conclusions
In the majority of our patients, there was no short-term hemodynamic benefit of flap stimulation; therefore, we conclude that the efficacy of cardiomyoplasty may be a consequence of a passive “girdling effect,” which limits the progression of ventricular enlargement and further deterioration of ejection fraction.
Sensitization of Human Atrial 5-HT
4
Receptors by Chronic β-Blocker Treatment
Authors: Sanders Louise , Lynham James A. , Bond Brian , del Monte Federica , Harding Sian E. , Kaumann Alberto J.
Published: June 2012

Background
Chronic treatment of patients with β-blockers induces β
2
-adrenergic receptor hyperresponsiveness in atrium and sinoatrial node. To investigate whether other atrial G
s
protein–coupled receptors also become hyperresponsive after chronic treatment with β-blockers, we investigated 5-HT
4
receptors in tissues and myocytes, which mediate serotonin-evoked increases of both contractile force and cAMP levels.

Methods and Results
Isolated right atrial strips from patients who had been chronically treated or not treated with a β-blocker were set up to contract. In tissues from β-blocker–treated patients (n=27), the maximum inotropic response to serotonin was 56±3% (mean±SEM) of the effect elicited by (−)-isoproterenol (200 μmol/L) compared with a response of 19±6% in tissues from non–β-blocker–treated patients (n=13) (
P
<.001). The responsiveness of the tissues to Ca
2+
was unchanged by chronic β-blocker treatment. Serotonin (1 and 10 μmol/L) increased tissue cAMP levels, the increase with 10 μmol/L being significantly greater (
P
<.05) in tissues from β-blocker–treated (n=9) than in non–β-blocker–treated (n=7) patients. In paced atrial myocytes, serotonin caused concentration-dependent increases in contraction. Myocytes obtained from atria of β-blocker–treated patients were more sensitive (
P
<.01) to the effects of serotonin (−log EC
50
, 7.9±0.2 mol/L; n=12) than myocytes obtained from non–β-blocker–treated patients (−log EC
50
, 7.3±0.2 mol/L, n=12). Chronic β-blocker treatment had no effect on forskolin-evoked myocyte responses. Carbachol (1 μmol/L) suppressed the effects of both serotonin (n=6) and (−)-isoproterenol (n=6) in the same atrial myocyte.

Conclusions
Chronic treatment of patients with β-blockers causes atrial 5-HT
4
receptor inotropic hyperresponsiveness and enhanced serotonin-evoked increases in cAMP levels. This may be due to modified cross talk between 5-HT
4
receptors, β-adrenergic receptors, and muscarinic receptors.
Primary Ventricular Fibrillation Is Associated With Increased Paced Right Ventricular Electrogram Fractionation
Authors: Saumarez R.C. , Heald S. , Gill J. , Slade A.K.B. , de Belder M. , Walczak F. , Rowland E. , Ward D.E. , Camm A.J.
Published: June 2012

Background
The mechanisms of spontaneous ventricular fibrillation (primary VF) in patients without structural heart disease are obscure. A new technique has shown that in patients with hypertrophic cardiomyopathy conduction of fractionated ventricular paced beats, recorded at several right ventricular sites, is prolonged in individuals who have suffered a VF arrest, and this may reveal one component of a reentrant substrate. Patients with primary VF were studied with the same methods to determine whether similar abnormalities are present in this group.

Methods and Results
Nine patients with primary VF were studied by pacing one right ventricular (RV) site by use of a constant drive train with an extrastimulus inserted every third beat and reducing the extrastimulus coupling interval (S1S2 interval) by 1 ms on each occasion while recording at three other sites. The delay of each fractionated potential in the high-pass–filtered electrograms in response to the extrastimulus was determined and used to form conduction curves of delay versus the S1S2 interval. These curves were repeated by pacing each RV site in turn and recording from the other three sites. The curves were characterized by determining the S1S2 interval at which electrogram components increased in delay by 0.75 ms/20 ms reduction in S1S2 interval and the increase in electrogram duration between a coupling interval of 350 ms and 1 ms above refractoriness. Seven control patients were studied using the same method. The mean increase in electrogram duration in VF patients was 13 ms (range, 3 to 23 ms) compared with 4 ms (range, −2 to 14 ms) in unaffected control patients. The extrastimulus coupling interval at which delay increased was 318 ms (range, 293 to 334 ms) in VF patients and 274 ms (range, 265 to 284 ms) in control patients (
P
<.01). There was no difference between the number of fractionated potentials in VF patients and control patients.

Conclusions
In primary VF patients, the individual potentials within fractionated electrograms have increased delays when compared with control patients. This may identify one component of a reentrant arrhythmic substrate.