bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Imaging in Coronary Artery Disease
Authors: van der Wall Ernst E. , Vliegen Hubert W. , de Roos Albert , Bruschke Albert V.G.
Published: June 2012

Abstract
The cardiovascular applications of nuclear magnetic resonance (MR) techniques in coronary artery disease have increased considerably in recent years. Technical advantages of MR imaging in comparison with other techniques are the excellent spatial resolution, the characterization of myocardial tissue, and the potential for three-dimensional imaging. This allows the accurate assessment of left ventricular mass and volume, the differentiation of infarcted tissue from normal myocardial tissue, and the determination of systolic wall thickening and regional wall motion abnormalities. Myocardial perfusion, metabolism, and inducible myocardial ischemia with the use of pharmacological stress also can be assessed by MR techniques. Future technical improvements in real-time imaging and development of noninvasive visualization of the coronary arteries and coronary artery bypasses will constitute a tremendous progress in clinical cardiology. Early detection and flow assessment of stenosed coronary arteries by MR angiography with the use of flow velocity measurements may outweigh the cost inherent to the MR imaging procedure. A particular strength of the MR technique is the potential to encompass cardiac anatomy, perfusion, function, metabolism, and coronary angiography in a single test. The replacement of multiple diagnostic tests with one MR test may have major effects on cardiovascular healthcare economics.
Preoperative Selection of Patients With Severely Impaired Left Ventricular Function for Coronary Revascularization
Authors: Vanoverschelde Jean-Louis J. , Gerber Bernhard L. , D'Hondt Anne-Marie , De Kock Martine , Dion Robert , Wijns William , Melin Jacques A.
Published: June 2012

Background
Both thallium imaging and low-dose dobutamine echocardiography have been proposed to predict the reversibility of left ventricular (LV) dysfunction in patients with coronary disease. The present study was designed to evaluate whether the use of these techniques during the preoperative assessment of coronary patients with depressed LV function can improve our ability to identify those likely to have improved LV function after surgery.

Methods and Results
Forty consecutive patients (age, 60±10 years) with coronary disease and an ejection fraction ≤35% underwent dobutamine echocardiography (10 μg/kg per minute) and exercise-redistribution-reinjection thallium single photon emission computed tomography (SPECT) before coronary revascularization by bypass surgery (n=33) or angioplasty (n=7). Recovery of LV function was evaluated by echocardiography 5.3±2.4 months after revascularization. According to the changes in end-systolic volume and ejection fraction after revascularization, the patients were categorized into groups with (n=19) and without (n=21) postoperative functional improvement, defined as a >5% increase in ejection fraction and >10 mL decrease in end-systolic volume. Before revascularization, patients with improved postoperative function had smaller end-diastolic volume and less wall motion abnormalities than those with persistent dysfunction. They also showed greater improvement of wall motion score with dobutamine (6.1±2.4 versus 1.8±4.2 grades,
P
<.001) and smaller thallium defect score after exercise (38±12 versus 47±14 grades,
P
=.04). Discriminant analysis selected the improvement in wall motion score with dobutamine and baseline end-diastolic volume as independent predictors of postoperative recovery. Consideration of both parameters allowed prediction of functional outcome in 84% of the patients with and 81% of those without postoperative improvement.

Conclusions
Among the parameters commonly available before surgery in coronary patients with depressed LV function, the maintenance of significant inotropic reserve, the severity of LV remodeling, and the magnitude of the perfusion defect after exercise can predict the reversal of LV dysfunction after revascularization.
Isoflurane Attenuates cAMP-Mediated Vasodilation in Rat Microvessels
Authors: Park K.W. , Dai H.B. , Lowenstein E. , Darvish A. , Sellke F.W.
Published: June 2012

Background
Endothelium-dependent vasodilation mediated by cGMP is known to be attenuated by the inhalational anesthetic isoflurane. The present study examines the effect of isoflurane on β-adrenergic and cAMP-mediated vasodilation.

Methods and Results
Fifty-three subepicardial coronary arteries (diameter, 103±13 μm) from Wistar rats were studied in vitro in a pressurized (40 mm Hg), no-flow state with use of optical density video detection system. After preconstriction of vessels with the thromboxane A
2
analogue U46619 10
−6
mol/L, concentration response curves to the nonselective β-adrenergic agonist isoproterenol, the G
S
protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase inhibitor RO20-1724 were obtained either in the presence or absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls.

Conclusions
Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.
Effects of Aortopulmonary Collaterals on Cerebral Cooling and Cerebral Metabolic Recovery After Circulatory Arrest
Authors: Kirshbom Paul M. , Skaryak Lynne A. , DiBernardo Louis R. , Kern Frank H. , Greeley William J. , Gaynor J. William , Ungerleider Ross M.
Published: June 2012

Background
Aortopulmonary collaterals (APC) have been associated with an increased risk of choreoathetosis after deep hypothermic circulatory arrest (DHCA). To study the effects of APC on cerebral hemodynamics and metabolism before and after DHCA, a piglet model was developed.

Methods and Results
Protocol 1: Eight 4- to 6-week-old piglets underwent placement of a left subclavian–to–main pulmonary artery shunt. Control shunts (n=4) were ligated, APC shunts (n=4) were left patent. All animals were placed on cardiopulmonary bypass (CPB) and cooled in identical fashion for 20 minutes. Temperature probes were placed in the nasopharynx, cortex, and deep brain. Control animals achieved significantly lower temperatures in all three areas by the end of cooling (17.5°C versus 20.1°C, 19.0°C versus 22.3°C, and 17.5°C versus 21.0°C, respectively,
P
<.005). Protocol 2: Six control and six APC animals were instrumented as described. All were placed on CPB, cooled to 18°C, arrested for 90 minutes, and rewarmed to 37°C. Cerebral blood flow (CBF) was measured with radioactive microspheres while warm on CPB, after cooling, and after rewarming. Arterial and sagittal sinus blood gases and CBF were used to calculate the cerebral metabolic rate of oxygen consumption (CMRO
2
). Both CBF and CMRO
2
were significantly higher after rewarming to 37°C in control versus APC animals (28±3 versus 14±2 mL/100 g per minute and 1.72±0.21 versus 1.04±0.14 mL O
2
/100 g per minute, respectively,
P
<.05).

Conclusions
APC decrease the rate of cerebral cooling on CPB and even if temperature is controlled result in increased cerebral metabolic derangement after DHCA. Patients with such collaterals may need additional measures to optimize cerebral protection.
In-Hospital and Long-term Outcome After Reoperative Coronary Artery Bypass Graft Surgery
Authors: Weintraub William S. , Jones Ellis L. , Craver Joseph M. , Grosswald Ralph , Guyton Robert A.
Published: June 2012

Background
Increasingly over the past several years, patients have returned after coronary surgery for reoperative procedures, and the experience has become substantial. In this report, we describe immediate- and long-term outcomes after reoperative coronary artery bypass graft surgery.

Methods and Results
The source of data was the clinical database at Emory University. The surgical procedure and statistical methods were standard. Data were collected prospectively and entered into a computerized database. Follow-up was by letter, telephone, or hospital records documenting additional events resulting in readmission. In-hospital correlates of survival were determined by logistic regression, and long-term correlates were determined by Cox model analysis. There were 2030 patients with a mean age of 61 and a mean of 7.8±4.1 years since the first surgery. The mean ejection fraction was close to 50%, and the majority had three-vessel or left main disease. Urgent or emergency surgery was required in 16.6%. The internal mammary was used in 60.1%. Q-wave myocardial infarctions occurred in just over 5%. Neurological events increased from 1.2% at less than age 50 to 4.1% at more than age 70. The hospital mortality increased from 5.7% at less than age 50 to 10% at more than age 70, with an overall rate of 7.0%. Mortality was 5.7% for elective, 10.9% for urgent, and 16.4% for emergency cases. Angina was noted at follow-up in 41.3%. Urgent or emergency surgery, reduced ejection fraction, hypertension, older age, and female sex were univariate and multivariate correlates of in-hospital death. Diabetes was a univariate correlate only. Five- and 10-year survival rates were 76% and 55%, respectively. Five- and 10-year myocardial infarction–free survival rates were 63% and 40%, respectively. By 12 years, few patients were free of cardiac events. The univariate and multivariate correlates of long-term mortality were older age, reduced ejection fraction, hypertension, diseased vessels, presence of diabetes, congestive failure, and emergency surgery, with a strong trend for female sex. The use of the internal mammary artery was not a correlate for long-term mortality.

Conclusions
Patients undergoing reoperative procedures have higher mortality initially and at long term than patients undergoing a first procedure. Expected mortality based on covariates may help in the decision of whether to perform reoperative coronary artery bypass graft surgery.
Prevention of Arterial Thrombosis by Adenovirus-Mediated Transfer of Cyclooxygenase Gene
Authors: Zoldhelyi Pierre , McNatt Janice , Xu Xiao-Ming , Loose-Mitchell David , Meidell Robert S. , Clubb Fred J. , Buja L. Maximilian , Willerson James T. , Wu Kenneth K.
Published: June 2012

Background
Prostacyclin is an important vasoprotective molecule. It inhibits platelet aggregation, monocyte interaction with endothelium, and smooth muscle cell lipid accumulation. Vascular cyclooxygenase-1 (COX-1) is the rate-limiting step in prostacyclin synthesis. The objective of this study was to determine whether adenovirus-mediated transfer of COX-1 could restore COX-1 activity, augment prostacyclin synthesis, and prevent thrombus formation in a porcine carotid angioplasty model.

Methods and Results
Human COX-1 cDNA driven by a cytomegalovirus promoter was constructed into a replication-defective adenovirus 5 vector by homologous recombination. Recombinant adenovirus without a foreign gene (Ad-RR) and buffer were included as controls. Recombinant Ad-LacZ was used for marking the transfected cells in vivo. In the in vitro experiments, cultured human endothelial cells (ECs) and porcine arterial smooth muscle cells (SMCs) were incubated with Ad-COX-1 for 2 hours and 6-keto-PGF
1α
level and the transgene expression were determined 72 hours after infection. In the in vivo experiments, recombinant adenoviruses were directly instilled into angioplasty-injured porcine carotid arteries for 30 minutes. Cyclic flow changes were monitored for 10 days and thrombus formation was examined histologically thereafter. Transgene expression and prostaglandin I
2
(PGI
2
) synthesis by the injured arteries were determined. Cultured ECs infected with Ad-COX-1 produced a fivefold to eightfold increase in PGI
2
, and the transgene expression in cultured porcine SMCs was demonstrated by Northern analysis. Direct administration of Ad-COX-1 at a dose of 3×10
10
pfu completely inhibited carotid cyclic flow changes and thrombus formation accompanied by a fourfold increase in PGI
2
synthesis by the injured arteries 10 days after infection, whereas Ad-COX-1 at a lower dose, 5×10
9
pfu, had no antithrombotic effects when compared with Ad-RR vector and buffer controls.

Conclusions
Adenovirus-mediated transfer of COX-1 to angioplasty-injured carotid arteries was efficacious in augmenting PGI
2
synthesis and was associated with an inhibition of thrombosis when a relatively high titer of adenovirus was instilled.
Elaboration of Type-1 Plasminogen Activator Inhibitor From Adipocytes
Authors: Lundgren Craig H. , Brown Steven L. , Nordt Thomas K. , Sobel Burton E. , Fujii Satoshi
Published: June 2012

Background
Obesity is known to predispose to attenuated fibrinolysis attributable to increased concentrations in plasma of type-1 plasminogen activator inhibitor (PAI-1), the primary physiological inhibitor of endogenous fibrinolysis. PAI-1 is present in neointimal vascular smooth muscle cells and lipid-laden macrophages.

Methods and Results
The present study was designed to determine whether PAI-1 expression occurs in adipose tissue as well, thereby potentially contributing to increased cardiovascular risk associated with obesity. 3T3-L1 preadipocytes were differentiated into adipocytes by exposing them to isobutylxanthine (0.5 mmol/L) and dexamethasone (0.25 μmol/L) over 7 days and incubated for 24 hours with transforming growth factor-β (TGF-β), known to augment PAI-1 synthesis in several cell types and to be released from platelets when they are activated. TGF-β increased PAI-1 activity in the conditioned media of the 3T3-L1–derived cells in a concentration-dependent fashion without significantly affecting cell proliferation. Western blotting and immunoprecipitation of
35
S-labeled PAI-1 showed that the increased PAI-1 activity paralleled increased PAI-1 protein. Northern blotting showed that increased PAI-1 mRNA preceded increased accumulation of PAI-1 activity and protein in the conditioned media. Furthermore, TGF-β (10 ng/g body wt) administered in vivo increased PAI-1 activity in mouse plasma and PAI-1 mRNA expression in mouse adipose tissue.

Conclusions
Increased plasma PAI-1 activity in obese human subjects may result from PAI-1 release from an increased mass of adipose tissue, particularly in association with thrombosis and elaboration of TGF-β from platelet α-granules into the circulation. The increased PAI-1 may exacerbate vascular disease by shifting the balance between thrombosis and thrombolysis toward thrombosis and consequently exposing luminal surfaces of vessels to mitogens associated with microthrombi over protracted intervals.
Lysis of Adult Ventricular Myocytes by Cells Infiltrating Rejecting Murine Cardiac Allografts
Authors: Wagoner Lynne E. , Zhao Liping , Bishop D. Keith , Chan Sherri , Xu Shixuan , Barry William H.
Published: June 2012

Background
Immunologic mechanisms that mediate myocardial cell injury during rejection are not fully understood. We therefore investigated whether cells that infiltrate rejecting cardiac allografts are capable of directly injuring myocytes and whether this injury resembles that produced by cytotoxic T lymphocytes (CTLs) that are generated in a mixed lymphocyte reaction (MLR).

Methods and Results
Heart-infiltrating cells (HICs) were isolated from murine heterotopic BALB/c cardiac allografts undergoing rejection 6 to 8 days after transplantation into C57BL/6 mice. An in vitro model system of cultured adult murine ventricular myocytes was developed to facilitate investigation of cell-mediated myocyte injury. Isolated adult myocytes were incubated with either HICs or MLR effector cells, and myocyte death was quantified by counting the number of rod-shaped myocytes excluding trypan blue. The frequency of donor-reactive CTLs was similar in the HIC and MLR populations, as assessed by limiting dilution analysis. However, HICs were less efficient at killing donor-strain myocytes than were MLR cells. CTL-mediated cell lysis occurred by 6 hours, whereas myocyte injury produced by HICs was more gradual, with considerable cytotoxicity occurring between 12 and 24 hours. Furthermore, whereas MLR cells lysed only donor-strain myocytes, HIC lysed donor, third-party, and syngeneic myocytes. Treatment of MLR cells and HICs with anti-CD8 antibody plus complement produced a much greater inhibition of MLR cytotoxicity than of HIC cytotoxicity.

Conclusions
These data demonstrate that only a small component of myocyte injury mediated by allograft-infiltrating cells can be ascribed to CTLs within the infiltrating cell population. These findings suggest that cell types associated with a delayed-type hypersensitivity response, as well as CTLs, cause myocyte injury during cardiac rejection.
Persistent Elevation of Plasma Insulin Levels Is Associated With Increased Cardiovascular Risk in Children and Young Adults
Authors: Bao Weihang , Srinivasan Sathanur R. , Berenson Gerald S.
Published: June 2012

Background
Hyperinsulinemia has been considered to be a potent cardiovascular risk factor. The present investigation examines persistently elevated fasting insulin levels from childhood to young adulthood and its influence on cardiovascular risk factors.

Methods and Results
A longitudinal cohort was constructed from two cross-sectional surveys in a community-based population over an 8-year period: 1606 individuals (39% were black) aged 5 to 23 years participated in the first survey. Stability in rankings (persistence) of insulin levels was shown by the presence of significant correlations between year 1 and year 8 values (
r
=.23 to .36,
P
<.0001), with a greater magnitude in older subjects. Compared with subjects with levels of insulin consistently in the lowest quartile, those with levels always in the highest quartile showed higher (
P
<.001) levels of body mass index (+9 kg/m
2
), triglycerides (+58 mg/dL), LDL cholesterol (+11 mg/dL), VLDL cholesterol (+8 mg/dL), glucose (+9 mg/dL), systolic blood pressure (+7 mm Hg), and diastolic blood pressure (+3 mm Hg); lower (
P
<.001) levels of HDL cholesterol (−4 mg/dL); and higher (
P
<.05) prevalence of parental history of diabetes (3.3-fold) and hypertension (1.2-fold). There were 739 young adults aged 20 to 31 years at follow-up. As adults, individuals with consistently elevated insulin versus those with consistently decreased insulin had increased (
P
<.05) prevalence of obesity (36-fold), hypertension (2.5-fold), and dyslipidemia (3-fold), which was attributed to both baseline insulin and change of insulin from baseline to follow-up. In addition, clustering of these risk factors was stronger (
P
<.05) in adults with persistent insulin elevation.

Conclusions
Elevated insulin levels persist from childhood through young adulthood, resulting in a clinically relevant adverse cardiovascular risk profile in young adults.
Low-Molecular-Weight Heparinoid Orgaran Is More Effective Than Aspirin in the Prevention of Venous Thromboembolism After Surgery for Hip Fracture
Authors: Gent M. , Hirsh J. , Ginsberg J.S. , Powers P.J. , Levine M.N. , Geerts W.H. , Jay R.M. , Leclerc J. , Neemeh J.A. , Turpie A.G.G.
Published: June 2012

Background
The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals.

Methods and Results
Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti–Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative
125
I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran (
P
=.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran (
P
=.137; 95% confidence interval, −30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin (
P
=.10). There was one major bleed in the Orgaran group compared with four in the aspirin group.

Conclusions
This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.
Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model
Authors: Sheridan Frank M. , Cole Paul G. , Ramage David
Published: June 2012

Background
Prompt reperfusion of ischemic myocardium or myocardium that is in the process of becoming infarcted is a cornerstone of current therapy for coronary artery disease. Paradoxically, experimental evidence suggests that cardiac damage may be caused by the reperfusion itself. Leukocyte attachment to the coronary vascular endothelium during reperfusion may be an initiating step in this detrimental process. Leukocyte adhesion to microvascular endothelium has never been demonstrated directly in a cardiac model of ischemia and reperfusion.

Methods and Results
Fluorescent videomicroscopy through a special “floating” objective that allows a series of lenses to move in unison with the beating dog heart was used on the left ventricular surface of open-chest dogs. Epicardial microvessels (25 to 130 μm), in focus throughout the cardiac cycle, were recorded after infusion of acridine orange (to fluorescently label leukocytes) during either 1 hour of ischemia followed by 2 hours of reperfusion, 3 hours of ischemia, or 3 hours of no ischemia. The amount of net fluorescence recorded along microvessel walls, which represented leukocyte accumulation, significantly increased in dogs during reperfusion (n=8) compared with the same time period in the animals that were kept ischemic (n=5) (21.0±3.8 versus 10.9±4.5 gray scale;
P
=.0001). The rapid increase in fluorescence during reperfusion was also significantly different from values in the same group during the preceding period of ischemia (21.0±3.8 versus 5.1±2.1 gray scale;
P
=.0001), whereas no significant increase was seen over the same time periods in the animals that remained ischemic throughout the protocol.

Conclusions
Reperfusion, compared with ischemia alone, promotes the rapid accumulation of leukocytes in the coronary microvasculature of dogs.
Cycle Length Dynamics and Spatial Stability at the Onset of Postinfarction Monomorphic Ventricular Tachycardias Induced in Patients and Canine Preparations
Authors: Vinet Alain , Cardinal René , LeFranc Pierre , Hélie François , Rocque Pierre , Kus Teresa , Pagé Pierre
Published: June 2012

Background
The aim of this study was to determine whether cycle length (CL) variations at the onset of monomorphic ventricular tachycardias follow distinctive patterns.

Methods and Results
We retrospectively analyzed 59 monomorphic ventricular tachycardias induced in 40 patients in whom intraoperative mapping was performed with 63 epicardial and 64 endocardial electrograms recorded simultaneously. Activation times and CL were determined at each electrode site over several beats (36±10 beats, mean±SD) starting with the first after programmed stimulation. In the majority of the tachycardias, CL variations were accounted for by fitting to an exponential function: CL=CL
s
+A
e

−
b/τ

, where CL
s
is the stable CL, b is beat number, τ is the time constant (in beat number), and A is the magnitude of CL relaxation. A decelerating trend (with reference to rate) (negative A) accounted for 21 tachycardias, an accelerating trend in rate (positive A) accounted for 12 tachycardias, and 4 others displayed a double dynamic behavior, with an initial acceleration followed by a decelerating trend in rate. Among the ventricular tachycardias that were not fitted to exponential models, 12 showed a constant trend and 10 others showed irregular CL fluctuations. The monomorphic character of the tachycardias was established by principal-component analysis, which also indicated that CL dynamics associated with the accelerating and decelerating trends may be related to shortening or prolongation of activation times, respectively, occurring in equal proportion at all recording sites. In canine preparations in which reentry circuits could be mapped with high resolution, CL showed an accelerating trend in rate when circus movement of excitation occurred around a transmural scar in muscle generating unipolar electrograms with relatively high −dV/dt
max
, and a decelerating trend in rate occurred when functional reentry occurred in muscle generating unipolar electrograms with depressed −dV/dt
max
.

Conclusions
Beat-to-beat CL variations may occur at the onset of sustained monomorphic ventricular tachycardia as a result of uniform acceleration or deceleration of activation times while the overall activation pattern remains constant. The associated initial trends in the rate of sustained monomorphic ventricular tachycardia follow typical patterns that might provide “signatures” corresponding to reentry substrates with distinctive functional properties.
Quantification of Volumetric Coronary Blood Flow With Dual-Energy Digital Subtraction Angiography
Authors: Molloi Sabee , Ersahin Atila , Tang Jerry , Hicks James , Leung Cyril Y.
Published: June 2012

Background
As a solution to the well-documented problems associated with visual interpretation of coronary arteriograms, more physiological methods of assessing coronary artery stenosis are being investigated. Volumetric coronary blood flow (BF) can be a valuable aid in the analysis of functional significance of arterial obstruction.

Methods and Results
The left anterior descending coronary artery (LAD) of 15 anesthetized pigs (40 to 50 kg) was dissected free from the epicardium in its proximal portion, and a transit-time ultrasound flow probe of the appropriate size was applied. A vascular occluder was positioned distal to the flow probe for flow adjustments. Contrast injections (2 to 4 mL/s for 3 seconds) were made into the left main coronary artery during image acquisition with a motion-immune dual-energy digital subtraction angiography (DE DSA) system. Tissue-suppressed energy-subtracted images were used to generate time-density curves. BF measurements were made in the LAD vascular bed with use of the time-density curve, with consideration that blood was momentarily replaced with contrast during the injection. In 19 comparisons, the mean BF, measured with the use of DE DSA, correlated extremely well with the mean ultrasound flow (DE DSA=0.90 ultrasound+3.10 mL/min,
r
=.96). Also, contrast injection increased the BF by an average of only 15% during the image-acquisition time interval.

Conclusions
Accurate BF measurements can be made with motion-immune DE DSA. The BF measurements can be completed before the onset of significant changes in BF due to contrast injection. Furthermore, it is possible to make the BF measurements during routine coronary arteriography.
Myocardial Perfusion Patterns Related to Thrombolysis in Myocardial Infarction Perfusion Grades After Coronary Angioplasty in Patients With Acute Anterior Wall Myocardial Infarction
Authors: Ito Hiroshi , Okamura Atsunori , Iwakura Katsuomi , Masuyama Tohru , Hori Masatsugu , Takiuchi Shin , Negoro Shinji , Nakatsuchi Yoshiaki , Taniyama Yoshiaki , Higashino Yorihiko , Fujii Kenshi , Minamino Takazo
Published: June 2012

Background
Epicardial coronary flow is occasionally reduced even after coronary intervention despite the absence of vessel obstruction in patients with acute myocardial infarction. Our aim was to clarify the cause and outcomes of radiocontrast slow filling in patients with reperfused acute anterior myocardial infarction by assessing microvascular damage with the use of myocardial contrast echocardiography (MCE) and functional outcomes.

Methods and Results
We carefully reviewed the cineangiograms of 86 patients who achieved coronary revascularization within 12 hours of the onset and underwent MCE before and soon after recanalization with the intracoronary injection of sonicated microbubbles. Antegrade coronary flow after recanalization was graded by two observers based on Thrombolysis in Myocardial Infarction (TIMI) trial flow grades. Left ventricular ejection fraction was measured on the day of infarction and 1 month later. TIMI grade 2 was observed in 18 patients (21%), and the other 68 patients manifested TIMI grade 3 after recanalization. All patients with TIMI 2 showed substantial MCE no reflow, whereas only 11 patients (16%) with TIMI 3 showed MCE no reflow. Functional improvement was worse in patients with TIMI 2 than in those with TIMI 3 (TIMI 2, 38±8% versus 40±8%,
P
=NS [acute versus late]; TIMI 3, 44±13% versus 55±13%,
P
<.001). Among patients with TIMI 3, significant functional improvement was observed only in patients with MCE reflow (MCE reflow, 46±13% versus 57±12%,
P
<.001; MCE no reflow, 35±11% versus 45±12%,
P
=NS).

Conclusions
Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.
Long-term Angiotensin-Converting Enzyme Inhibition With High-Dose Enalapril Retards Nitrate Tolerance in Large Epicardial Arteries and Prevents Rebound Coronary Vasoconstriction In Vivo
Authors: Münzel Thomas , Bassenge Eberhard
Published: June 2012

Background
Rebound myocardial ischemia develops in patients with unstable or stable angina pectoris after sudden cessation of nitroglycerin therapy. Long-term nitroglycerin infusion is associated with increases in plasma renin activity and catecholamine release rates, both of which may lead to excess angiotensin II and α-adrenergic–mediated vasoconstriction, particularly on withdrawal of nitroglycerin.

Methods and Results
Chronically instrumented dogs were treated for 5 days with nitroglycerin (1.5 μg·kg
−1
·min
−1
IV) alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor enalapril (0.1 mg/kg two times daily or 1 mg/kg). With long-term nitroglycerin therapy, the left anterior circumflex artery was maximally dilated 4 hours after the start of nitroglycerin infusion (9.5±0.6%) and returned to baseline levels within the third day of treatment (baseline, 2.52±0.07 mm; day 3, 2.55±0.07 mm;
P
=NS), indicating a complete loss of nitroglycerin-induced coronary vasodilatation. Nitroglycerin infusion also was accompanied by a transient increase in plasma renin activity. Sudden withdrawal of nitroglycerin infusion caused a progressive constriction of the left anterior circumflex artery, which peaked 4 hours after nitroglycerin infusion cessation (−7.8±0.2%). This occurred in the absence of elevated plasma renin activity. Concomitant treatment with high-dose enalapril (1 mg·kg
−1
·d
−1
) markedly reduced the degree of tolerance and prevented the rebound constriction on cessation of nitroglycerin therapy.

Conclusions
Long-term ACE inhibition with high-dose enalapril reduces nitroglycerin tolerance and prevents rebound vasoconstriction in coronary arteries. These phenomena were not associated with an activated circulating renin-angiotensin system. This observation suggests that during long-term nitroglycerin treatment, intrinsic abnormalities of the vascular smooth muscle may have developed that are suppressed by concomitant ACE inhibitor therapy. The present study also favors a combination of nitroglycerin and ACE inhibitors to maintain nitrate sensitivity of the vasculature during long-term nitroglycerin treatment.
Six-Month Clinical and Angiographic Outcome of the New, Less Shortening Wallstent in Native Coronary Arteries
Authors: Ozaki Yukio , Keane David , Ruygrok Peter , van der Giessen Willem J. , de Feyter Pim , Serruys Patrick W.
Published: June 2012

Background
The new, less shortening, self-expanding Wallstent is characterized by longitudinal flexibility, a protective membrane, a low profile, and a customized range of diameters (3.5 to 6.0 mm). The recent modification of the braiding angle of the Wallstent has resulted in a new device with less shortening on expansion and a concomitant reduction in radial force. We hypothesized that the enforced mechanical remodeling produced by the selection of an oversized Wallstent might result in improved accommodation of subsequent reactive intimal hyperplasia and prevention of chronic recoil of the vessel.

Methods and Results
To prove this hypothesis, we recently implanted 44 new, less shortening Wallstents in 35 native coronary arteries in 35 patients with acute or threatened closure after balloon angioplasty, according to a strategy of oversizing of Wallstent diameter and complete coverage of the lesion length. The initial and 6-month follow-up angiograms were analyzed with a computer-based quantitative coronary angiography (QCA) system. Acute gain (minimal luminal diameter [MLD] post minus MLD pre) and late loss (MLD post minus MLD at follow-up) were examined. Stent deployment was successful in 44 of 44 attempts (100%). Nominal stent diameter used was 1.40 mm larger than the maximal vessel diameter. One patient (3%) with a dilated but unstented lesion proximal to the stented segment sustained a subacute occlusion on day 1 associated with myocardial infarction. Event-free survival at 30 days after stent implantation was 97% (34 of 35 patients). Of the 34 patients eligible for 6-month angiographic follow-up, 3 who were asymptomatic declined repeat angiography. MLD (and percent diameter stenosis [% DS]) changed from 0.83±0.50 mm (72%) pre through 3.06±0.48 mm (15%) post to 2.27±0.74 mm (28%) at follow-up. Acute gain was 2.23±0.63 mm, and late loss was 0.78±0.61 mm. Angiographic restenosis (>50% DS) was observed in 5 of 31 patients (16%) at 6 months, all of whom underwent repeat angioplasty. Thus, the overall event-free survival at 6-month follow-up was 83% (29 of 35 patients).

Conclusions
The oversized Wallstent implantation with complete coverage of the lesion length conveyed a favorable 6-month clinical and angiographic outcome. The large acute gain obtained by the Wallstent afforded greater accommodation of the subsequent late loss. The enforced mechanical remodeling by oversized new Wallstents may result in prevention of acute and chronic recoil of the vessel wall and subsequently a lower restenosis rate at follow-up.
Power Law Behavior of RR-Interval Variability in Healthy Middle-Aged Persons, Patients With Recent Acute Myocardial Infarction, and Patients With Heart Transplants
Authors: Bigger J. Thomas , Steinman Richard C. , Rolnitzky Linda M. , Fleiss Joseph L. , Albrecht Paul , Cohen Richard J.
Published: June 2012

Background
The purposes of the present study were (1) to establish normal values for the regression of log(power) on log(frequency) for RR-interval fluctuations in healthy middle-aged persons, (2) to determine the effects of myocardial infarction on the regression of log(power) on log(frequency), (3) to determine the effect of cardiac denervation on the regression of log(power) on log(frequency), and (4) to assess the ability of power law regression parameters to predict death after myocardial infarction.

Methods and Results
We studied three groups: (1) 715 patients with recent myocardial infarction; (2) 274 healthy persons age and sex matched to the infarct sample; and (3) 19 patients with heart transplants. Twenty-four–hour RR-interval power spectra were computed using fast Fourier transforms and log(power) was regressed on log(frequency) between 10
−4
and 10
−2
Hz. There was a power law relation between log(power) and log(frequency). That is, the function described a descending straight line that had a slope of ≈−1 in healthy subjects. For the myocardial infarction group, the regression line for log(power) on log(frequency) was shifted downward and had a steeper negative slope (−1.15). The transplant (denervated) group showed a larger downward shift in the regression line and a much steeper negative slope (−2.08). The correlation between traditional power spectral bands and slope was weak, and that with log(power) at 10
−4
Hz was only moderate. Slope and log(power) at 10
−4
Hz were used to predict mortality and were compared with the predictive value of traditional power spectral bands. Slope and log(power) at 10
−4
Hz were excellent predictors of all-cause mortality or arrhythmic death. To optimize the prediction of death, we calculated a log(power) intercept that was uncorrelated with the slope of the power law regression line. We found that the combination of slope and zero-correlation log(power) was an outstanding predictor, with a relative risk of >10, and was better than any combination of the traditional power spectral bands. The combination of slope and log(power) at 10
−4
Hz also was an excellent predictor of death after myocardial infarction.

Conclusions
Myocardial infarction or denervation of the heart causes a steeper slope and decreased height of the power law regression relation between log(power) and log(frequency) of RR-interval fluctuations. Individually and, especially, combined, the power law regression parameters are excellent predictors of death of any cause or arrhythmic death and predict these outcomes better than the traditional power spectral bands.
A Randomized Comparison of Combined Ticlopidine and Aspirin Therapy Versus Aspirin Therapy Alone After Successful Intravascular Ultrasound–Guided Stent Implantation
Authors: Hall Patrick , Nakamura Shigeru , Maiello Luigi , Itoh Akira , Blengino Simonetta , Martini Giovanni , Ferraro Massimo , Colombo Antonio
Published: June 2012

Background
Previous studies have shown that it is feasible to withhold anticoagulation after a successful intracoronary stent procedure with a low incidence of stent thrombosis. The importance of specific antiplatelet agents when stenting is performed without anticoagulation is unknown.

Methods and Results
After successful intravascular ultrasound–guided stenting, 226 patients were randomly assigned to receive either aspirin therapy alone (n=103) or a combination of ticlopidine and short-term aspirin therapy (n=123). Primary angiographic and clinical end points were stent thrombosis, death, myocardial infarction, the need for postprocedure coronary artery bypass surgery or repeated angioplasty, and significant medication side effects requiring termination of the medication within the first month of a successful procedure. At 1 month, the rate of stent thrombosis was 2.9% in the aspirin only group and 0.8% in the ticlopidine-aspirin group (
P
=.2). Cumulative major clinical events after successful stenting occurred in 3.9% of the patients in the aspirin group and in 0.8% in the ticlopidine-aspirin group (
P
=.1). There were no medication side effects in the aspirin group; in the combined ticlopidine-aspirin group, medication side effects occurred in 3 patients (
P
=.2).

Conclusions
At 1 month, there was no difference in the incidence of stent thrombosis or other clinical end points between the two poststent antiplatelet regimens. However, the relatively small size of the study and the low incidence of thrombosis events may have contributed to the failure to detect differences in angiographic and clinical end points between the two groups.
Myocardial Rubidium-82 Tissue Kinetics Assessed by Dynamic Positron Emission Tomography as a Marker of Myocardial Cell Membrane Integrity and Viability
Authors: vom Dahl Juergen , Muzik Otto , Wolfe Edwin R. , Allman Christine , Hutchins Gary , Schwaiger Markus
Published: June 2012

Background
Recent reports have demonstrated the clinical use of rubidium-82 chloride (Rb-82) in combination with positron emission tomography (PET) not only as a tracer of myocardial blood flow but also as a marker of cell membrane integrity using static imaging early and late after tracer injection. The purpose of this study was to compare myocardial Rb-82 kinetics assessed by dynamic PET imaging as a marker for tissue viability with regional fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with coronary artery disease.

Methods and Results
Twenty-seven patients with angiographically proven coronary artery disease and 5 subjects with a low likelihood for coronary artery disease underwent dynamic PET imaging under resting conditions using Rb-82 and FDG. Both image sequences served as input data for a semiautomated regional analysis program. This program generated polar maps representing Rb-82 tissue half-life and FDG utilization assessed by Patlak’s approach. Myocardial tissue viability was visually determined from static Rb-82 and FDG images. Regions were categorized as normal, ischemically compromised, and scar tissue. Their coordinates were subsequently copied to the functional polar maps for further analyses. In normal subjects, Rb-82 tissue half-life was homogeneous throughout the left ventricle (90±11 seconds). In coronary patients, differences between Rb-82 tissue half-lives in normal and scar tissue were highly significant (95±10 and 57±15 seconds, respectively;
P
<.0001). FDG uptake in these two tissue groups was 78±12% and 40±13%, respectively (
P
<.0001). Ischemically compromised tissue with reduced perfusion but maintained FDG uptake displayed an Rb-82 half-life of 75±9 seconds, indicating active cellular tracer retention, which was significantly different from scar tissue. Overall agreement of tissue categorization as either viable or scar was 86% between Rb-82 kinetics and FDG utilization. In a subgroup of 11 patients with all three tissue types within one image set, Rb-82 tissue half-life discriminated between normal, ischemic, and scar tissue (97±9, 75±9, and 60±15 seconds, respectively;
P
<.01).

Conclusions
This study demonstrated a significant relationship between cell membrane integrity as assessed by dynamic Rb-82 PET imaging and myocardial glucose utilization as a marker for tissue viability. In regions with reduced perfusion, Rb-82 kinetics was different in compromised but metabolically active and irreversibly injured myocardium. The predictive value of this approach must be evaluated in follow-up studies.
Midwall Left Ventricular Mechanics
Authors: de Simone Giovanni , Devereux Richard B. , Koren Michael J. , Mensah George A. , Casale Paul N. , Laragh John H.
Published: June 2012

Background
An appreciable proportion of asymptomatic hypertensive patients have depressed left ventricular (LV) performance that is identified by midwall shortening/end-systolic stress relations but not by indexes that use endocardial shortening. It has not been established, however, whether depressed midwall ventricular performance has prognostic implications.

Methods and Results
Echocardiographic endocardial and midwall LV fractional shortening/circumferential end-systolic stress relations in 294 hypertensive patients were analyzed as predictors of the occurrence of cardiovascular morbid events that occurred in 50 patients (including 14 deaths) during a 10-year mean follow-up. Patients with initially lower midwall but not endocardial shortening, either in absolute terms or as a percentage of predicted from observed end-systolic stress, were more likely to suffer morbid events than those with initially normal values (
P
<.004). Cardiovascular events occurred in 29 of 100 patients (29%) and death in 10 of 100 patients (10%) among those who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 21 of 194 (11%) and 4 of 194 (2.1%) of the remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3;
P
<.0001; and odds ratio, 5.3; 95% CI, 1.6 to 17.3;
P
<.006, respectively). In logistic analysis, increasing age, high LV mass, high systolic blood pressure, and low values for an interaction term between LV mass index and midwall shortening independently predicted cardiovascular events (.04<
P
<.001); increasing age, low midwall LV shortening as a percentage of predicted, and high value of the interaction term predicted the occurrence of cardiac death (.004<
P
<.0002). Survival analysis controlling for age confirmed that low midwall shortening independently predicted cardiac morbidity or death, especially in the subgroup of patients with LV hypertrophy.

Conclusions
Depressed midwall shortening is a predictor of adverse outcome in arterial hypertension; the combination of higher LV mass and lower midwall shortening identifies individuals at markedly increased risk.
Effect of Slow Pathway Ablation on Ventricular Rate During Atrial Fibrillation
Authors: Kreiner Gerhard , Heinz Gottfried , Siostrzonek Peter , Gössinger Heinz David
Published: June 2012

Background
Catheter ablation of the posteroseptal right atrium has been proposed for control of ventricular rate in patients with tachycardic atrial fibrillation (AF). However, the exact mechanism of rate control is unclear. Because the ablation site corresponds to the location of the slow pathway in patients with AV nodal reentry tachycardia (AVNRT), we investigated whether selective ablation of this posterior AV nodal input can provide a sufficient reduction in heart rate during AF.

Methods and Results
In 30 patients with AVNRT, conduction properties of the AV nodal pathways were determined before and after slow pathway ablation. AF was induced by burst pacing at baseline and after ablation, and the mean ventricular cycle length was determined. After slow pathway ablation, the mean ventricular cycle length during AF increased (449±98 versus 515±129 milliseconds,
P
<.01). At baseline, the mean ventricular cycle length correlated with the Wenckebach cycle length of both the slow (
r
=.90) and fast (
r
=.86) pathways. After ablation, the mean ventricular cycle length was extremely well determined by the Wenckebach cycle length of the fast pathway (
r
=.94). However, the slope of the regression line was significantly steeper compared with baseline (1.50 versus 0.77,
P
<.0001), illustrating that the reduction in ventricular rate was not as evident if the fast pathway had a short Wenckebach cycle length.

Conclusions
Selective elimination of the slow pathway reduces ventricular rate during AF. However, in patients with a short Wenckebach cycle length of the anterior AV nodal input that causes tachycardic AF, this effect may be insufficient to provide adequate control of ventricular rate.