bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Recovery in Bileaflet Heart Valve Prostheses
Authors: Vandervoort Pieter M. , Greenberg Neil L. , Pu Min , Powell Kimerly A. , Cosgrove Delos M. , Thomas James D.
Published: June 2012

Background
We investigate pressure recovery in central and side orifices of St Jude valves and the effect of mitral versus aortic position on the relation between Doppler- and catheter-derived pressure gradients.

Methods and Results
Maximum, transvalvular, and net pressure gradients are calculated and compared with Doppler-derived gradients in an in vitro model. Pressure recovery and pressure loss coefficients are calculated. Simultaneous Doppler and catheter gradients are obtained intraoperatively in five patients undergoing mitral valve replacement. Centerline Doppler gradients correspond closely with maximum catheter gradients but are higher than transvalvular and net pressure gradients. Thirty-six percent of the initial pressure drop is recovered between the valve leaflets and is independent of valve size or configuration. A variable amount of postvalvular pressure recovery is observed depending on aortic or mitral configuration. Side orifice velocities are 85±4% of the centerline velocities. Incorporation of the pressure loss coefficient in the simplified Bernoulli equation shows close agreement between centerline Doppler gradients and transvalvular gradients (
r
=.99,
y
=1.11
x
−0.19).

Conclusions
Gradients across the St Jude valve measured by Doppler ultrasound are higher than transvalvular or net catheter gradients due to downstream pressure recovery. This is more marked for Doppler gradients based on centerline velocities than side orifice velocities and is more pronounced for valves in an aortic than a mitral configuration. Therefore, to be comparable with invasive transvalvular catheter gradients, either Doppler gradients should be calculated based on side orifice velocity measurements or the Doppler gradient calculation should include the pressure loss coefficient when based on central orifice velocities.
Catheter Ablation of the Mitral Isthmus for Ventricular Tachycardia Associated With Inferior Infarction
Authors: Wilber David J. , Kopp Douglas E. , Glascock DO Dennis N. , Kinder Charles A. , Kall John G.
Published: June 2012

Background
Intraoperative mapping studies suggest that an isthmus of myocardium between the mitral valve annulus and the border of inferior myocardial infarction may play a role in the genesis of ventricular tachycardia. We examined the frequency with which a slow conduction zone within the mitral isthmus was critical to the maintenance of ventricular tachycardia associated with remote inferior infarction in patients undergoing catheter ablation.

Methods and Results
In 4 of 12 patients, a critical zone of slow conduction was identified within the mitral isthmus. In each of these patients, two characteristic and morphologically distinct tachycardias were induced: a left bundle (rS in V
1
, R in V
6
), left superior axis morphology and a right bundle (R in V
1
, QS in V
6
), right superior axis morphology (cycle length, 610 to 320 ms). In each patient, a zone of slow conduction, shared by both morphologies, was characterized by diastolic potentials with electrogram-QRS intervals of 85 to 161 ms (21% to 47% of tachycardia cycle length) and entrainment with concealed fusion during pacing associated with stimulus-QRS intervals of 81 to 400 ms (20% to 91% of tachycardia cycle length). In each patient, a single radiofrequency energy application at the shared site of slow conduction eliminated inducibility of both morphologies. During follow-up of 1 to 11 months, no patient had recurrent tachycardia.

Conclusions
The mitral isthmus contains a critical region of slow conduction in some patients with ventricular tachycardia after inferior myocardial infarction, providing a vulnerable and anatomically localized target for catheter ablation. Characteristic tachycardia morphologies may provide clinical markers for this underlying mechanism.
Effects of ACE Inhibitors on Circulating Versus Cardiac Angiotensin II in Volume OverloadInduced Cardiac Hypertrophy in Rats
Authors: Ruzicka Marcel , Skarda Vaclav , Leenen Frans H.H.
Published: June 2012

Background
Cardiac volume overload by an aortocaval shunt increases left ventricular end-diastolic pressure (LVEDP) and plasma and cardiac renin activity and results in LV hypertrophy. To a similar extent, the angiotensin-converting enzyme (ACE) inhibitors enalapril and quinapril prevent the increase in LVEDP. However, only quinapril attenuates the development of LV hypertrophy. We hypothesize that a low affinity of enalapril for cardiac ACE results in continuing generation of cardiac angiotensin II and thus hypertrophic growth of cardiomyocytes.

Methods and Results
In the present study, we assessed plasma and cardiac angiotensins I and II 1 and 7 days after aortocaval shunt and the effects of enalapril and quinapril started 3 days before surgery on plasma and cardiac angiotensin I and II at the same time points. Aortocaval shunt increased plasma angiotensin II at 1 day by 180%, but only a small increase (by 40%) persisted at 7 days. Aortocaval shunt increased LV angiotensin II by 100% and 65% at 1 and 7 days, respectively. Both blockers similarly prevented the increase in plasma angiotensin II by aortocaval shunt at both time points. In contrast, only quinapril prevented the rise in LV angiotensin II induced by shunt at 1 and 7 days.

Conclusions
Aortocaval shunt increases LVEDP and plasma and cardiac angiotensin II and results in LV hypertrophy. Only prevention of the increase in LVEDP and in plasma and cardiac angiotensin II attenuates the development of LV hypertrophy, consistent with the concept that angiotensin II is involved in the development of cardiac hypertrophy by aortocaval shunt by both hemodynamic and cardiac trophic effects. This study is the first to show that differences in affinity for cardiac ACE may determine the effect of ACE inhibitors on cardiac angiotensin II and therefore cardiac hypertrophy.
Metabolic Adaptation to a Gradual Reduction in Myocardial Blood Flow
Authors: Arai Andrew E. , Grauer Susan E. , Anselone Cheryl G. , Pantely George A. , Bristow J. David
Published: June 2012

Background
Studies during 20% to 50% reductions in regional coronary blood flow have revealed a number of metabolic and functional adaptations that suggest the heart downregulates energy requirements and contractility in response to ischemia. In contrast to prior studies of sudden changes in coronary blood flow, we tested whether the heart could reduce ATP consumption commensurate with a gradual decrease in coronary blood flow or whether transient metabolic abnormalities are a necessary trigger in this process.

Methods and Results
From 0 to 35 minutes, mean left anterior descending coronary artery blood flow was reduced by ≈1% per minute in 10 acutely anesthetized and instrumented swine. Coronary blood flow then was held constant between 35 and 60 minutes at the resulting 35% net blood flow reduction. Although systemic hemodynamics remained stable, a significant decrease in regional left ventricular systolic wall thickening developed (from control value of 45±11% to 18±11% at 60 minutes,
P
<.001) without a sustained decrease in the phosphorylation potential (as assessed by a <2% decrease in either the transmural or subendocardial phosphocreatine-to-ATP ratio) and with minimal myocardial lactate production (4±44 μmol · min
−1
· 100 g
−1
).

Conclusions
Metabolic markers of ischemia such as ratio of phosphocreatine to ATP, ATP content, lactate content, and lactate production were blunted during this protocol of gradually worsening ischemia. Thus, contractile abnormalities of mild ischemia can develop with minimal metabolic evidence of ischemia. The downregulation of myocardial energy requirements can almost keep pace with the gradual decline in coronary blood flow.
Human Heart–Infiltrating T-Cell Clones From Rheumatic Heart Disease Patients Recognize Both Streptococcal and Cardiac Proteins
Authors: Guilherme L. , Cunha-Neto E. , Coelho V. , Snitcowsky R. , Pomerantzeff P. M. A. , Assis R. V. , Pedra F. , Neumann J. , Goldberg A. , Patarroyo M. E. , Pileggi F. , Kalil J.
Published: June 2012

Background
β-Hemolytic streptococcal infection in developing countries still causes thousands of cases of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal–M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte–dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions.

Methods and Results
We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein–derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4
+
, and one is CD8
+
.

Conclusions
The presence of heart–M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.
Coronary Sinus Morphology in Patients With Atrioventricular Junctional Reentry Tachycardia and Other Supraventricular Tachyarrhythmias
Authors: Doig J. Colin , Saito Junichi , Harris Louise , Downar Eugene
Published: June 2012

Background
Coronary sinus access by electrode catheters is easier in patients with atrioventricular junctional reentry tachycardia (AVJRT) than in patients with other supraventricular tachyarrhythmias. The reason for this has not been addressed.

Methods and Results
The size and shape of the proximal coronary sinus were measured in 15 patients with AVJRT and 14 control subjects after angiographic visualization. Coronary sinus dimensions, morphology, and angle of origin from the right atrium were measured. The proximal coronary sinus in patients with AVJRT was larger than in the control population. The mean ostium diameter was 12.2±2 mm compared with control dimensions of 8.5±1.5 mm,
P
=.00001. At a distance of 5 mm from the ostium, the coronary sinus measured 10.2±1.8 mm compared with 8.1±1.9 mm,
P
=.007. The dilatation persisted 10 mm into the coronary sinus, with a measurement of 9±1.4 mm compared with 7.6±2 mm,
P
=.04. In 73% of AVJRT patients, the proximal coronary sinus had the appearance of a wind sock. This morphology was seen only in 7% of control patients, in whom the coronary sinus was tubular (in 93%). There was considerable interindividual variability in the angle of origin.

Conclusions
The proximal coronary sinus in patients with AVJRT was significantly different from a control population. The ostium was 44% larger and remained more dilated to at least 10 mm from the ostium. The appearance was like a wind sock in AVJRT patients and tubular in the control patients. These findings may have important implications for arrhythmia pathogenesis in such patients.
Isolated Congenital Complete Atrioventricular Block in Adult Life
Authors: Michaëlsson Magnus , Jonzon Anders , Riesenfeld Tomas
Published: June 2012

Background
The prognosis of congenital complete atrioventricular block (CCHB) is usually considered favorable in adults. This belief is based on studies comprising a limited number of patients and with rather short observation times. In the present study, the natural history of the disease was investigated by a prospective follow-up through decades of adult life of patients with a large group having well-defined CCHB without structural heart disease.

Methods and Results
The diagnostic criteria of CCHB proposed by Yater were applied. Patients registered as having CCHB in 1964, supplemented by younger patients all without symptoms during their first 15 years of life, were selected. The study was limited to patients with isolated, complete, permanent block. An interview was conducted with all patients and clinical follow-up data obtained. There were finally 102 patients, 61 women and 41 men. In November 1994, the time of observation, after the age of 15 years in survivors, was between 7 and 30 years. The mean age at follow-up or at death was 38 years, median age 37 years, and range 16 to 66 years. Stokes-Adams (SA) attacks occurred in 27 patients, in 8 with a fatal outcome. The first attack was fatal in 6 of these 8 patients. Nineteen survived and a pacemaker (PM) was implanted thereafter. Another 8 patients received a PM because of repeated fainting spells, and 27 others have had a PM implanted for other reasons such as fatigue, effort dyspnea, dizziness, ectopies during exercise tests, mitral regurgitation, and a low ventricular rate (VR). VR decreased with age, with a mean rate at 15 years of 46 beats per minute (bpm), at 16 to 20 years of 43 bpm, at 21 to 30 years of 41 bpm, at 31 to 40 years of 40 bpm, and after 40 years of age of 39 bpm. SA attacks occurred in all 7 patients with prolonged QT
c
time. Low VR at rest or at work, presence of bundle-branch block pattern, low working capacity, and ectopies at rest and/or during effort were not statistically significant risk factors. SA attacks occurred in 6 patients without any of these signs. Mitral regurgitation developed in 16 patients and 4 died. A PM reduced the risk of death. A change to a lower degree of block occurred in 6 patients.

Conclusions
Prophylactic PM treatment is recommended even for symptom-free adults with CCHB because of the high incidence of unpredictable SA attacks with considerable mortality from first attacks, a gradually decreasing VR, significant morbidity, and a high incidence of “acquired” mitral insufficiency.
Antithrombotic Effects of Orally Active Synthetic Antagonist of Activated Factor X in Nonhuman Primates
Authors: Yokoyama Toru , Kelly Andrew B. , Marzec Ulla M. , Hanson Stephen R. , Kunitada Satoshi , Harker Laurence A.
Published: June 2012

Background
Since activated factor X (FXa) has a central role in hemostasis and thrombosis, it is an attractive target for antithrombotic strategies. Accordingly, we evaluated the relative antihemostatic and antithrombotic effects of an orally active amidinoaryl propanoic acid inhibitor of FXa, APAP, in baboons.

Methods and Results
With a two-component thrombogenic device that induced the concurrent formation of both arterial-type platelet-rich and venous-type fibrin-rich thrombus when interposed in chronic exteriorized arteriovenous (AV) femoral shunts flowing at 40 mL/min, thrombus formation was compared for oral versus parenteral APAP by measurement of
111
In-platelet deposition,
125
I-fibrin accumulation, thrombotic obstruction of flow, and circulating levels of blood biochemical markers of thrombosis. The direct infusion of APAP (120 μg/min) into AV shunts proximal to thrombogenic devices for 1 hour achieved local drug levels of 4.3±0.4 mg/L and substantially reduced the accumulation of platelets and fibrin in the formation of venous-type fibrin-rich thrombus (
P
<.01) but not in the formation of platelet-rich arterial-type thrombus (
P
>.1). APAP was subsequently removed from plasma with plasma clearance rates of T
50
α of 6.3 minutes and T
50
β of 99 minutes. The oral administration of APAP (50 mg/kg) produced peak plasma levels of 3.7±1.4 μg/mL at 30 minutes and gradually declining plasma levels over about 6 to 8 hours, with bioavailability estimated to be approximately 5% to 12%. Oral APAP decreased platelet deposition (
P
<.01) and fibrin accumulation (
P
<.05) in venous-type thrombus but failed to decrease platelet or fibrin accumulation in arterial-type thrombus (
P
>.1 in both cases). Oral and infused APAP prolonged the activated partial thromboplastin time and prevented thrombus-dependent elevations in plasma fibrinopeptide A, thrombin–antithrombin III complex, β-thromboglobulin, and platelet factor 4 levels. Additionally, APAP produced dose-dependent inhibition of FXa bound to thrombus on segments of vascular graft interposed in exteriorized AV shunts for 15 minutes.

Conclusions
An oral synthetic antagonist of FXa, APAP, inhibits the formation of venous-type fibrin-rich thrombus by inactivating bound and soluble FXa without impairing platelet hemostatic function.
Electrical Resistances of Interstitial and Microvascular Space as Determinants of the Extracellular Electrical Field and Velocity of Propagation in Ventricular Myocardium
Authors: Fleischhauer Johannes , Lehmann Lilly , Kléber André G.
Published: June 2012

Background
In myocardial ventricular tissue, extracellular electrical resistance (r
o
) is an important determinant of propagation velocity (Θ) and the magnitude of the extracellular bipolar electrogram (ΔV
o
). The extracellular space is composed of two compartments, the vascular space and the interstitial space. To assess the electrical equivalent of this compartmentation in the ventricular myocardium and its effect on r
o
, Θ, and ΔV
o
, electrical cable analysis was performed in an arterially perfused rabbit papillary muscle.

Methods and Results
Vascular resistivity was changed from 75 to 86 to 143 and to 221 Ω/cm by variation of hematocrit in the perfusate from 0% to 10% to 40% and to 60%. As a means to vary the volume of the interstitial space and with this as its resistivity, colloid osmotic pressure (COP) in the perfusate was changed from 9 to 36 and to 94 mm Hg by altering the dextran concentration in the perfusate from 10 to 40 to 80 g/L. Decreasing COP had a marked effect on r
o
(56% decrease), ΔV
o
(decrease from 61 to 42 mV), Θ (increase from 48 to 59 cm/s), and the diameter of the muscle fiber (increase of 12%). If COP was increased from 36 to 94 mm Hg, r
o
(by 35%) and ΔV
o
(from 62 to 75 mV) increased; Θ and diameter showed no significant changes. In contrast, alterations of intravascular electrical resistivity in a range from 75 to 221 Ω/cm did not induce any significant changes in r
o
, ΔV
o
, Θ, and diameter of the preparations.

Conclusions
We conclude from our data that (1) the microvascular tree in ventricular myocardium is electrically insulated to a large degree from the interstitial space and that (2) electrical current flow in the extracellular space during excitation is confined to the narrow, anisotropic interstitial space.
Automated Echocardiographic Measures of Right Ventricular Area as an Index of Volume and End-Systolic Pressure-Area Relations to Assess Right Ventricular Function
Authors: Oe Masahiro , Gorcsan John , Mandarino William A. , Kawai Akihiko , Griffith Bartley P. , Kormos Robert L.
Published: June 2012

Background
On-line determination of right ventricular (RV) volume to assess its function is clinically difficult. Echocardiographic automated border detection measures of left ventricular (LV) cavity area have been shown to reflect changes in volume, and pressure-area relations have been used to estimate LV contractility. The potential for RV cavity area to estimate changes in volume and to assess RV function, however, has not been evaluated. Accordingly, the objective of this study was to determine the relation between echocardiographic automated border-detected RV cross-sectional area and true volume and to assess the potential for end-systolic pressure-area relations to estimate RV function in an isovolumically contracting isolated canine heart preparation.

Methods and Results
Eight excised dog hearts with both right and left intraventricular balloons were perfused in an ex vivo apparatus in which both ventricular volumes were controlled independently. RV area data from the level of the left midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. RV volumes were varied from 9.4±3.9 to 43.8±6.9 mL at each of three different LV volume ranges (low range, 12.5±3.8 mL; medium range, 23.9±5.6 mL; and high range, 37.5±5.4 mL). The variation of RV area during isovolumic contraction, which we called deformational area change, was considerable (1.49±0.68 cm
2
mean±SD) but did not change significantly with changing RV and LV volumes. Linear regression analysis correlated the maximum, minimum, and mean automated border-detected RV area during isovolumic contraction with absolute volume. A predominantly linear relation was observed, with the group mean
r
=.98 (
y
=0.16
x
+0.97; SEE=0.21 cm
2
). The effect of LV volume on RV area-volume relation was a significant parallel downward shift (
P
<.05) by increases in LV volume. End-systolic pressure-area and pressure-volume relations using simultaneously RV pressure were both highly linear and covaried with changing LV volume.

Conclusions
Echocardiographic automated border-detected RV area reflects changes in RV volume under a constant LV volume, and the derived end-systolic pressure-area relation has potential for on-line assessment of RV function.
Relation Between Ischemia Time, Infarct Size, and Left Ventricular Function in Humans
Authors: Hasche Edmund T. , Fernandes Clyne , Freedman S. Ben , Jeremy Richmond W.
Published: June 2012

Background
Experimental studies indicate that duration of ischemia is a major determinant of myocardial infarct size, but only limited information is available about the relation between ischemia time and infarct size in individual patients. This prospective study sought to document the role of ischemia time as a determinant of infarct size in humans.

Methods and Results
We studied 61 patients (50 men, 11 women) 57±11 years old admitted with a first infarct (31 anterior, 30 inferior) who underwent continuous 12-lead ECG monitoring to document ischemia time. Infarct size (32-point QRS score on day 7) and changes in regional myocardial wall motion (echocardiography) during the following month were related to ischemia time. Among patients with <3 hours of ischemia (n=16), mean infarct size on day 7 was 21±13% of potential infarct size; in patients with 3 to 6 hours of ischemia (n=23), infarct size was 38±18% of potential (
P
<.05 versus 0 to 3 hours of ischemia); and in patients with 6 to 9 hours of ischemia (n=10), infarct size was 66±14% of potential (
P
<.05 versus 3 to 6 hours). In contrast, the 12 patients with an ischemia time >9 hours had a final infarct size of 77±10% of potential (
P
<.01 versus 3 to 6 hours). Multivariate regression identified size of risk region, duration of ischemia, and degree of initial ST-segment elevation as independent predictors of infarct size, of which the most important variable was ischemia time. The regression models accurately predicted both individual absolute infarct size (
R
2
=.83) and individual infarct/risk ratio (
R
2
=.74). Patients with <6 hours of ischemia exhibited significant recovery of myocardial wall motion by day 7 (wall motion score, 2.1±1.4 versus 5.7±3.2 on day 1,
P
<.01). Patients with 6 to 9 hours of ischemia had some recovery by 1 month (score, 6.3±4.4 versus 10.9±3.8 on day 1,
P
<.01), but patients with >9 hours of ischemia had little recovery of wall motion by 1 month (score, 10.3±4.5 versus 12.8±3.1 on day 1,
P
<.05).

Conclusions
Measurement of ischemia time allows improved prediction of infarct size in humans. Significant myocardial salvage and functional recovery may be achieved by reperfusion up to 9 hours after coronary occlusion. Continuous ST-segment monitoring should be used to measure ischemia time and guide interventions to reperfuse the infarct artery.
Subclinical Disease as an Independent Risk Factor for Cardiovascular Disease
Authors: Kuller L.H. , Shemanski L. , Psaty B.M. , Borhani N.O. , Gardin J. , Haan M.N. , O’Leary D.H. , Savage P.J. , Tell G.S. , Tracy R.
Published: June 2012

Background
The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study.

Methods and Results
A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes.

Conclusions
The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.
Long-term (5-Year) Changes in HDL Cholesterol in Cardiac Rehabilitation Patients
Authors: Warner James G. , Brubaker Peter H. , Zhu Ying , Morgan Timothy M. , Ribisl Paul M. , Miller Henry S. , Herrington David M.
Published: June 2012

Background
It is unknown whether the benefits of a cardiac rehabilitation program on HDL cholesterol (HDL-C) are equally achieved in men and women. To study this, we compared changes in HDL-C and other lipids in a large group of men and women participating in a cardiac rehabilitation program for up to 5 years.

Methods and Results
We compared changes in HDL-C and other fasting lipids in 553 men and 166 women participating in a cardiac rehabilitation program at baseline and then annually for up to 5 years. Patients exercised 3 days a week at 70% to 85% of their maximum heart rate predetermined by a symptom-limited treadmill test. Aerobic capacity was estimated in metabolic equivalents (METs), and percent body fat was determined by skin-fold measurements. Baseline HDL-C, LDL cholesterol (LDL-C), and total cholesterol were significantly higher in women, whereas the ratio of total cholesterol to HDL-C was lower. Although both men and women showed an increase in HDL-C after 1 year (10% and 7%, respectively), only the women’s level continued to increase over 5 years (20% versus 5% for men,
P
=.03). The sex difference in change in HDL-C remained after adjustment for age and smoking. A nonsignificant trend toward a greater change in HDL-C in women existed after adjustment for baseline percent body fat and estimated METs. The change in the ratio of total cholesterol to HDL-C was also more favorable in women, with a 38% decrease over 5 years compared with a 14% decrease in men (
P
=.01). Total cholesterol decreased by 20% in women and 8% in men (
P
=.0001), whereas LDL-C dropped by 34% in women and 15% in men (
P
=.0001). There was no sex difference in change in triglycerides.

Conclusions
Women with heart disease who participate in a cardiac rehabilitation program may achieve greater lipid benefits over longer periods of time than previously demonstrated in men.
Alterations of Sarcoplasmic Reticulum Proteins in Failing Human Dilated Cardiomyopathy
Authors: Meyer Markus , Schillinger Wolfgang , Pieske Burkert , Holubarsch Christian , Heilmann Claus , Posival Herbert , Kuwajima Goro , Mikoshiba Katsuhiko , Just Hanjörg , Hasenfuss Gerd
Published: June 2012

Background
Previous studies provide considerable evidence that excitation-contraction coupling may be disturbed at the level of the sarcoplasmic reticulum (SR) in the failing human heart. Disturbed SR function may result from altered expression of calcium-handling proteins.

Methods and Results
Levels of SR proteins involved in calcium release (ryanodine receptor), calcium binding (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban) were measured by Western blot analysis in nonfailing human myocardium (n=7) and in end-stage failing myocardium due to dilated cardiomyopathy (n=14). The levels of the ryanodine receptor, calsequestrin, and calreticulin were not significantly different in nonfailing and failing human myocardium. Phospholamban protein levels (pentameric form) normalized per total protein were decreased by 18% in the failing myocardium (
P
<.05). However, phospholamban protein levels were not significantly different in failing and nonfailing myocardium when normalization was performed per calsequestrin. Protein levels of SR calcium ATPase, normalized per total protein or per calsequestrin, were decreased by 41% (
P
<.001) or 33% (
P
<.05), respectively, in the failing myocardium. Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by 37% (
P
<.05) and relative to phospholamban by 28% (
P
<.05).

Conclusions
Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban. These findings support the concept that reduced capacity of the SR to accumulate calcium may reflect a major defect in excitation-contraction coupling in human heart failure.
Endovascular Stents in the Pulmonary Circulation
Authors: Fogelman Rami , Nykanen David , Smallhorn Jeffrey F. , McCrindle Brian W. , Freedom Robert M. , Benson Lee N.
Published: June 2012

Background
The use of endovascular stents to relieve obstructions in the setting of non–balloon dilatable pulmonary artery stenosis has been encouraging. The benefits in management and the potential for restenosis, however, have not been defined. This study attempts to assess the impact of such implants on clinical outcomes and the pattern of stent incorporation within the vessel wall.

Methods and Results
Fifty-five balloon-expandable stents were implanted in 42 patients 6.1±4.7 years of age. Patients were followed prospectively (median, 15 months) and recatheterized 1 year after implantation. Thirty-eight patients had the implants positioned percutaneously (49 implants), while 4 patients (6 implants) had intraoperative implantations. There was a diameter increase in the stenotic area of 109±79% (
P
<.0001) and a gradient reduction of 74±26% (
P
<.0001). Twelve stents straddled the orifice of side-branch pulmonary arteries and reduced flow to the branch vessel acutely in 7 patients. Twenty-nine patients underwent recatheterization, and various degrees and locations of acquired intraluminal narrowing were observed in all cases, particularly in areas of diameter mismatch between the stented and nonstented vessels. Eleven patients had further dilation with diameter improvement. Of the 38 patients who underwent percutaneous implantation, planned surgery for pulmonary artery stenosis was avoided in 33 and deferred in 4 patients. One patient who was considered inoperable had stent implantation as a palliative procedure. Symptomatic improvement was reported in 27 patients, and 15 patients remained asymptomatic.

Conclusions
Endovascular stents have a role in the treatment of pulmonary artery stenoses and positively affect clinical care. The stenosis relief, however, may be tempered by the development of intraluminal stent obstruction, which may require redilation (15 of 55 stents) and mandates long-term follow-up.
Accumulation of Fetal Fibronectin mRNAs After Balloon Denudation of Rabbit Arteries
Authors: Bauters Christophe , Marotte Francoise , Hamon Martial , Oliviéro Patricia , Farhadian Farah , Robert Valérie , Samuel Jane Lyse , Rappaport Lydie
Published: June 2012

Background
Fibronectin (FN), a component of the extracellular matrix, influences cellular migration and differentiation. It is a prominent component of the extracellular matrix of normal arteries and is thought to play an important role in the pathogenesis of restenosis after angioplasty. FN exists in multiple forms that arise from a single RNA transcript that can be alternatively spliced. EIIIA- and EIIIB-containing FN mRNAs predominate in the embryo, whereas in the adult, most of the normal tissue FN lacks these domains. Since few data were available concerning pattern of expression of the different alternatively spliced forms of FN mRNA in arteries after endoluminal injury, we analyzed the expression of EIIIA and EIIIB FN isoforms at different times after experimental angioplasty.

Methods and Results
The spatial and temporal alterations in FN expression were studied in an in vivo model of endothelial denudation in the rabbit aorta and iliac artery by a combination of immunochemistry and in situ hybridization methods. Alternatively spliced forms of FN EIIIA and EIIIB were detected in the media and the adventitia of both types of vessels 24 to 48 hours after injury. Two weeks after injury, EIIIA and EIIIB mRNAs were found to accumulate within the luminal layers of the neointima. The cellular form of FN protein was not found until 2 weeks after the injury and accumulated in the inner part of the neointima.

Conclusions
These data demonstrate that FN upregulation is an early and long-lasting process after arterial injury. These results suggest that the induction of the embryonic FN isoforms may be involved in the restenotic process that follows balloon denudation of arteries.
Role of Thrombin Compared With Factor Xa in the Procoagulant Activity of Whole Blood Clots
Authors: Prager Nelson A. , Abendschein Dana R. , McKenzie Clark R. , Eisenberg Paul R.
Published: June 2012

Background
Thrombi are known to induce activation of the coagulation system, which may be a mechanism for progression of thrombosis and its recurrence after thrombolysis. This study was designed to characterize the relative role of thrombin and activated factor X (factor Xa) as mediators of procoagulant activity of whole blood clots in blood and plasma.

Methods and Results
Clots formed from human blood were incubated in recalcified (25 mmol/L CaCl
2
) citrated plasma or nonanticoagulated blood with increasing concentrations of recombinant desulfatohirudin (hirudin) to inhibit thrombin activity, recombinant tick anticoagulant peptide (TAP) or recombinant tissue factor pathway inhibitor (TFPI) to inhibit factor Xa, or heparin. Fibrinopeptide A (FPA) was assayed serially as an index of procoagulant (thrombin) activity. FPA generation was greatly accelerated by addition of clots to recalcified plasma (from 1251±211 ng/mL after 15 minutes without clot to 5916±1412 ng/mL with clot, n=7,
P
<.01) or whole blood (4803±761 ng/mL with clot compared with 546±233 without clot, n=5,
P
<.05) and was attenuated by inhibitors of thrombin (>90% inhibition of FPA with 0.05 μmol/L hirudin and 1.0 U/mL heparin) and factor Xa (>90% inhibition of FPA with 1.0 μmol/L TAP and 0.15 μmol/L TFPI) in a concentration-dependent manner. Preincubation of clots with tissue-type plasminogen activator sufficient to induce partial clot lysis increased the rate of thrombin-induced FPA generation by increasing the surface area of clot exposed to plasma. However, procoagulant activity induced by partially lysed clots was attenuated by lower concentrations of both thrombin and Xa inhibitors, presumably because access of the inhibitors to bound procoagulant molecules was facilitated. Comparable results were obtained with incubations in nonanticoagulated blood.

Conclusions
These results indicate that factor Xa is primarily responsible for the procoagulant activity of clots in vitro and suggest a potential molecular mechanism for the observed efficacy of inhibitors of factor Xa in preventing recurrent thrombosis after coronary thrombolysis.
Hemodynamic Mechanisms Responsible for Reduced Subendocardial Coronary Reserve in Dogs With Severe Left Ventricular Hypertrophy
Authors: Hittinger Luc , Mirsky Israel , Shen You-Tang , Patrick Thomas A. , Bishop Sanford P. , Vatner Stephen F.
Published: June 2012

Background
Reduced subendocardial coronary reserve is a hallmark of left ventricular hypertrophy (LVH). The goal of this study was to determine whether hemodynamic, as opposed to structural, mechanisms were responsible for the reduced subendocardial coronary reserve.

Methods and Results
The effects of near-maximal vasodilation with adenosine were examined in 10 conscious dogs with LVH (79% increase in ratio of LV weight to body weight) induced by aortic banding in puppies with and without preload reduction. At baseline, LV end-diastolic pressure, LV end-diastolic circumferential and compressive radial wall stresses, and LV myocardial blood flow were similar in dogs with LVH and sham-operated controls, while LV end-systolic circumferential wall stress tended to be greater in the LVH group compared with the control group. In control dogs, adenosine reduced LV circumferential end-systolic and end-diastolic wall stresses and compressive radial subendocardial wall stress; LV subendocardial blood flow increased (from 1.41±0.16 to 3.58±0.27 mL · min
−1
· g
−1
) and the ratio of subendocardial to subepicardial blood flow decreased from 1.30±0.07 to 0.69±0.05. In dogs with LVH, during adenosine infusion, LV circumferential end-systolic and end-diastolic wall stresses and LV radial subendocardial wall stresses remained elevated, the increase in LV subendocardial blood flow was significantly smaller (from 1.11±0.11 to 2.27±0.24 mL · min
−1
· g
−1
,
P
<.05), and the subendocardial/epicardial ratio fell to a lower level (from 1.22±0.17 to 0.35±0.03,
P
<.05). When LV wall stresses during adenosine were reduced in a subgroup of 5 dogs with LVH, the endocardium/epicardium ratio during adenosine infusion was no longer different from that in control dogs (0.63±0.11), nor was the level of subendocardial blood flow different (3.42±0.60 mL · min
−1
· g
−1
).

Conclusions
These data suggest that hemodynamic factors, eg, compressive forces, are an important component of the reduced subendocardial coronary reserve as opposed to structural alterations, even in the presence of severe LVH.
Genetic Variation on Chromosome 1 Associated With Variation in Body Fat Distribution in Men
Authors: Hegele Robert A. , Brunt J. Howard , Connelly Philip W.
Published: June 2012

Background
Interindividual variation in fat deposition in swine is determined by loci on porcine chromosome 4, which are contained in a region that is syntenic with part of the long arm of human chromosome 1. We hypothesized that genomic variation of chromosome 1q would be associated with variation in the ratio of waist-to-hip circumference in male North American Hutterites, a genetic isolate characterized by significant relatedness and sharing of environmental factors.

Methods and Results
In 316 male Hutterites, we tested for phenotype-genotype association of two DNA polymorphisms on chromosome 1q and the ratio of waist-to-hip circumference. We included control loci on 10 other chromosomes in the multivariate model. We observed that DNA variation on chromosome 1q was significantly associated with variation in the ratio of waist-to-hip circumference in men (
P
=.0029).

Conclusions
The association of DNA variation chromosome 1q with the ratio of waist-to-hip circumference in male Hutterites suggests that there are important structural elements in this genomic region that have a functional impact on body fat distribution.
Association of Coronary Disease With Segment-Specific Intimal-Medial Thickening of the Extracranial Carotid Artery
Authors: Crouse John R. , Craven Timothy E. , Hagaman Amy P. , Bond M. Gene
Published: June 2012

Background
Several investigators have evaluated relations between risk factors and intimal-medial thickness (IMT) of the extracranial carotid arteries and between IMT and clinical cardiovascular disease. Different indexes of IMT have been used as referents. We compared the strength of association of various IMT measurements with coronary artery disease as measured at coronary angiography.

Methods and Results
We quantified the mean of the IMT for 12 sites of the extracranial carotid arteries (common carotid, bifurcation, internal carotid, near and far walls, and left and right sides [mean aggregate]) as well as for various combinations of sites (eg, segment-specific means, far walls only, maximum of any site) in 270 patients with or free of coronary artery disease. Models including age and all the indexes of IMT identified the mean aggregate as the only variable independently associated with the status of coronary atherosclerosis for the group as a whole. Next most strongly correlated was the mean common plus bifurcation. When classification algorithms were tested for ability to correctly classify case patients and control subjects, the mean bifurcation, mean common plus bifurcation, and mean aggregate were most strongly related to case-control status; however, the predictive power of the mean common was also strong.

Conclusions
These data support use of the mean aggregate extracranial carotid IMT for correlation with the status of coronary atherosclerosis; however, the data also support use of the mean common plus bifurcation, since there is little increase in predictive power of the mean aggregate over this index. Use of the common carotid alone is also justifiable and may be preferable for certain analyses.
Magnetic Resonance Imaging Assessment of the Severity of Mitral Regurgitation
Authors: Hundley W. Gregory , Li Hong F. , Willard John E. , Landau Charles , Lange Richard A. , Meshack Benjamin M. , Hillis L. David , Peshock Ronald M.
Published: June 2012

Background
In the patient with mitral regurgitation who is being considered for valvular surgery, cardiac catheterization is usually performed to quantify the severity of regurgitation and to determine its influence on left ventricular volumes and systolic function. Magnetic resonance imaging (MRI) potentially provides a rapid, noninvasive method of acquiring these data. Thus, this study was done to determine whether MRI can reliably measure the magnitude of mitral regurgitation and evaluate the effect of regurgitation on left ventricular volumes and systolic function.

Methods and Results
Twenty-three subjects (14 women and 9 men 15 to 72 years of age) with (n=17) or without (n=6) mitral regurgitation underwent MRI scanning followed immediately by cardiac catheterization. The presence (or absence) of valvular regurgitation was determined, and left ventricular volumes and regurgitant fraction were quantified during each procedure. There was excellent correlation between invasive and MRI assessments of left ventricular end-diastolic (
r
=.95) and end-systolic (
r
=.95) volumes and regurgitant fraction (
r
=.96). All MRI examinations were completed in <28 minutes.

Conclusions
In the patient with mitral regurgitation, MRI compares favorably with cardiac catheterization for assessment of the magnitude of regurgitation and its influence on left ventricular volumes and systolic function.
Morning Peak in Ventricular Tachyarrhythmias Detected by Time of Implantable Cardioverter/Defibrillator Therapy
Authors: Tofler Geoffrey H. , Gebara Otavio C. E. , Mittleman Murray A. , Taylor Peter , Siegel William , Venditti Ferdinand J. , Rasmussen Carl A. , Muller James E. , Investigators for the CPI
Published: June 2012

Background
A morning peak in occurrence of sudden cardiac death has been identified in epidemiological studies, but the studies are subject to selection bias, with the exclusion of unwitnessed deaths, which are more likely to occur at night. The recent availability of implantable cardioverter/defibrillators that record the time of ventricular tachyarrhythmias requiring either pacing or shock therapy provides an opportunity to clarify the timing of ventricular tachyarrhythmias predisposing to sudden cardiac death. Analysis of the timing of arrhythmias in different patient subgroups, such as patients with poor left ventricular function, may provide further insight into the mechanism of onset of sudden cardiac death.

Methods and Results
We studied patients in whom a cardioverter/defibrillator (Ventak PRx) was implanted between September 1990 and September 1993 in US centers. Events that could be timed occurred in 483 patients. With an RR cycle length of 240 ms as a cutoff, corresponding to a heart rate of 250 beats per minute, episodes were categorized as rapid (n=1217) or less rapid (n=9266) ventricular tachyarrhythmias. A higher proportion of both rapid and less rapid ventricular tachyarrhythmias began in the late morning compared with other times of the day. The subgroup of patients with ejection fraction <20% at the time of implantation demonstrated a more uniform 24-hour distribution of tachycardias ≤250 beats per minute than patients with higher left ventricular ejection fraction.

Conclusions
Further investigation of the late morning peak and of precipitants of ventricular tachyarrhythmias by use of data from the implantable cardioverter/defibrillator may provide insight into the pathophysiological mechanisms causing sudden cardiac death.