bluuebunny/crossref_metadata_2025 huggingface dataset:
The Münster Heart Study (PROCAM)
Authors: Cullen Paul , Schulte Helmut , Assmann Gerd
Published: June 2012

Background
Some large epidemiological studies have shown an increase in mortality at low levels of total and LDL cholesterol. It has been speculated that low cholesterol levels may play a causative role in this association. To investigate this question, we analyzed all deaths occurring among middle-aged men in the Münster Heart Study (PROCAM), one of the largest prospective epidemiological studies of coronary heart disease risk markers in Europe.

Methods and Results
In the Münster Heart Study, 10 856 men aged 36 to 65 years at study entry (46.8±7.3 years [mean±SD]) were followed for 4 to 14 years (7.1±2.4 years). During this period, 313 deaths occurred−46 from myocardial infarction, 48 from suspected or definite sudden cardiac death, 14 from cerebrovascular disease, and 10 from other diseases of the circulatory system. There were 121 deaths from cancer and 33 deaths from violent causes (injuries in 16, suicide in 14, and homicide in 3 cases). Death in 29 cases occurred from other causes and was unexplained in 12 cases. Total cholesterol, LDL cholesterol, and the LDL/HDL ratio showed a J-shaped relationship with total mortality. At high total and LDL cholesterol concentrations, increased mortality was due to increased coronary deaths. At low total and LDL cholesterol concentrations, increased mortality was seen in smokers only and was explained by an increase in smoking-related cancer deaths.

Conclusions
The increase in mortality at low levels of total and LDL cholesterol among middle-aged men in the Münster Heart Study is explained by an increase in smoking-related cancer deaths among smokers.
Myocardial Infarction and Cardiac Mortality in the Bypass Angioplasty Revascularization Investigation (BARI) Randomized Trial
Authors: Chaitman Bernard R. , Rosen Allan D. , Williams David O. , Bourassa Martial G. , Aguirre Frank V. , Pitt Bertram , Rautaharju Pentti M. , Rogers William J. , Sharaf Barry , Attubato Michael , Hardison Regina M. , Srivatsa Sanjay , Kouchoukos Nicholas T. , Stocke Karen , Sopko George , Detre Katherine , Frye Robert
Published: June 2012

Background
Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA.

Methods and Results
The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23;
P
=.022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR=1.04, 95% CI, 0.65 to 1.66;
P
=.908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 (
P
<.001). MIs were more common after CABG during index hospitalization (
P
=.004), but in the PTCA group, they were more common after discharge (
P
<.001).

Conclusions
The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery.
Treatment of In-Stent Restenosis With Excimer Laser Coronary Angioplasty
Authors: Mehran Roxana , Mintz Gary S. , Satler Lowell F. , Pichard Augusto D. , Kent Kenneth M. , Bucher Theresa A. , Popma Jeffery J. , Leon Martin B.
Published: June 2012

Background
This study determined the clinical safety, mechanisms, and 6-month results of excimer laser angioplasty (ELCA)+adjunct PTCA for the treatment of in-stent restenosis and (via lesion matching) compared the results of ELCA+PTCA to PTCA alone.

Methods and Results
Using quantitative angiography (QCA) and intravascular ultrasound (IVUS), we studied 107 restenotic previously stented lesions in 98 patients before and after intervention. QCA measurements included minimum lumen diameter (MLD) and diameter stenosis (DS). IVUS measurements included stent, lumen, and intimal hyperplasia (IH=stent−lumen) cross-sectional areas (CSA) and volumes. In the 54 lesions treated with ELCA+PTCA, the MLD increased from 0.73±0.38 mm before ELCA to 2.10±0.47 mm after ELCA+PTCA (
P
<.0001); the DS decreased from 70±14% to 25±12% (
P
<.0001). By IVUS, the minimum lumen CSA increased from 1.58±0.78 mm
2
before ELCA to 6.34±1.75 mm
2
after ELCA+PTCA (
P
<.0001) as a result of an increase in minimum stent CSA from 7.70±2.41 to 9.10±2.60 mm
2
(
P
<.0001) and a decrease in IH CSA from 5.25±2.84 to 2.63±1.41 mm
2
(
P
<.0001). Volumetric analysis showed that tissue ablation (during ELCA) contributed 29±15%, tissue extrusion (during adjunct PTCA) contributed 31±14%, and additional stent expansion (during adjunct PTCA) contributed 40±16% to the overall lumen gain. There were no ELCA-related complications. Matched to lesions treated with PTCA alone, ELCA+PTCA resulted in greater lumen gain, more IH ablation/extrusion, larger final lumen CSA (IVUS), and a tendency for less frequent need for subsequent target vessel revascularization (TVR, 21% versus 38%,
P
=.0823).

Conclusions
ELCA safely and effectively ablates in-stent neointimal tissue. Adjunct PTCA extrudes neointimal tissue out of the stent and also further expands the stent. Compared with PTCA alone, ELCA+PTCA achieves better short-term and, potentially, better long-term results.
Prognostic Value of Bisoprolol-Induced Hemodynamic Effects in Heart Failure During the Cardiac Insufficiency BIsoprolol Study (CIBIS)
Authors: Lechat P. , Escolano S. , Golmard J. L. , Lardoux H. , Witchitz S. , Henneman J. A. , Maisch B. , Hetzel M. , Jaillon P. , Boissel J.-P. , Mallet A.
Published: June 2012

Background
To further evaluate the mechanism of β-blocker–induced benefits in heart failure, the relationships between bisoprolol-induced hemodynamic effects and survival were studied during the Cardiac Insufficiency BIsoprolol Study (CIBIS).

Methods and Results
In 557 patients studied, bisoprolol significantly reduced heart rate (−16.3±15.3 versus −1.6±13.4 bpm, respectively;
P
<.001) compared with placebo at 2 months after inclusion in the study. Heart rate change over time had the highest predictive value for survival (
P
<.01). Left ventricular fractional shortening (LVFS) significantly increased in the bisoprolol group compared with the placebo group 5 months after inclusion (+0.04±0.06 versus −0.001±0.05, respectively;
P
<.001; n=160). LVFS change over time was also significantly correlated with further survival (
P
<.02 by Cox analysis). Using a nonparametric approach, we demonstrated a significant interaction between study treatment group and LVFS over time. Patients who demonstrated improvement of LVFS over time (82% and 51% of patients in the bisoprolol and the placebo groups, respectively;
P
<.02) were at lower risk, but the hazard did not further decrease with a further increase of fractional shortening, and there was no significant difference between study treatment groups. Finally, it could be demonstrated that each of the three factors (heart rate change over time, LVFS change over time, and bisoprolol treatment) made a specific contribution to mortality rate.

Conclusions
Preservation of left ventricular function appears to play a key role in the bisoprolol-induced beneficial effects on prognosis in heart failure. Short-term β-blocker–induced cardiac effects could provide a means to identify those patients who will experience improved survival over the long term.
Antithrombin III Prevents and Rapidly Reverses Leukocyte Recruitment in Ischemia/Reperfusion
Authors: Ostrovsky Lena , Woodman Richard C. , Payne Derrice , Teoh Diane , Kubes Paul
Published: June 2012

Background
P-selectin has recently been shown to be essential for leukocyte rolling after the reperfusion of ischemic mesentery. However, the mediators responsible for neutrophil rolling in ischemic microvessels remain entirely unclear.

Methods and Results
Intravital microscopy was used to examine leukocyte kinetics in a feline mesentery ischemia/reperfusion model. Sixty minutes of ischemia followed by reperfusion caused a profound increase in leukocyte rolling and adhesion. Pretreatment with the endogenous antithrombotic agent antithrombin III (ATIII) infused as a bolus (250 U/kg) reduced neutrophil rolling and adhesion to preischemic levels during reperfusion. No effect was seen with heat-inactive ATIII. Importantly, ATIII posttreatment also significantly reduced neutrophil rolling and adhesion during reperfusion, suggesting that ATIII can reverse the leukocyte recruitment response induced by ischemia/reperfusion. Vascular permeability was also reduced by 50% after ATIII administration. To determine whether ATIII could reverse thrombin-induced rolling directly, neutrophil rolling was performed on human endothelium in flow chambers. Indeed, thrombin-induced rolling, but not histamine-induced rolling, could be rapidly reversed with ATIII on endothelium, suggesting that ATIII affects thrombin rather than directly affecting neutrophils or the endothelium.

Conclusions
This study demonstrates for the first time that thrombin plays an important role in ischemia-induced leukocyte rolling and adhesion and that ATIII can be used therapeutically postreperfusion to attenuate the leukocyte recruitment response in inflammation without the nonspecific effects associated with anti–adhesion molecule therapy.
Inhibition of Arterial Thrombosis by Recombinant Annexin V in a Rabbit Carotid Artery Injury Model
Authors: Thiagarajan Perumal , Benedict Claude R.
Published: June 2012

Background
The procoagulant effect of anionic phospholipid may play a major role in the development of arterial thrombosis.

Methods and Results
Annexin V, a calcium-dependent anionic-phospholipid–binding protein, was expressed and isolated from
Escherichia coli
and its antithrombotic effect examined in a rabbit carotid artery thrombosis model. A partially occlusive thrombus was formed in the left carotid artery by application of electric current to produce an ≈50% occlusion of the lumen. After the current was discontinued, flow ceased completely within 42±12 minutes (n=6) because of continuing platelet/fibrin thrombus formation. When annexin V was given at doses of 2.8 to 16.6 μg · kg
−1
· min
−1
for a period of 180 minutes, starting at the time the current was stopped, there was a dose-dependent inhibition of thrombus formation. At a dose of 5.6 μg · kg
−1
· min
−1
, blood flow remained patent throughout the infusion and for an additional 60 minutes after the infusion was stopped. In addition, there was a decrease in thrombus weight (16±7.4 versus 2.0±1.0 g),
125
I-fibrin deposition (≈45% reduction,
P
<.001), and
111
In-labeled platelet accumulation (≈43% reduction,
P
<.001). Prior mixing of annexin V with phosphatidylserine micelles abolished the antithrombotic effect of annexin V, whereas mixing with phosphatidylcholine micelles had no effect. The antithrombotic effect of annexin V was not associated with bleeding tendency, as judged by the amount of blood absorbed in a gauze pad placed in a surgical incision extending to the muscle tissue and by the standard template bleeding time.

Conclusions
These observations support a potentially important role for anionic phospholipid exposure in platelets in arterial thrombosis, and inhibition of this activity could be a novel target for therapy in coronary thrombosis and stroke and after angioplasty.
Coronary Risk Estimation and Treatment of Hypercholesterolemia
Authors: Simon Alain , Megnien Jean Louis , Levenson Jaime
Published: June 2012

Background
Evidence-based treatment of hypercholesterolemia currently recommended for rationalizing drug prescription requires justification of treatment by randomized trials, such as the West of Scotland Coronary Prevention Study (WOSCOPS) or the Scandinavian Simvastatin Survival Study (4S), and evaluation of its benefit from the estimation of the coronary risk of each patient.

Methods and Results
The latest European guidelines and Sheffield tables apply these principles and justify the decision to treat hypercholesterolemia if the Framingham coronary multivariate risk estimate is high enough, ie, >20% risk of coronary event at 10 years in the former and >1.5% risk of coronary death per year in the latter. Nevertheless, the practice of these two recent guidelines results in discrepancies in the decision to treat, because coronary morbidity was considered in one but mortality was considered in the other, and the risk required for treating may be extrapolated from different trials (4S or WOSCOPS).

Conclusions
Although the principle of targeting lipid-lowering treatment to high-risk subjects is unquestioned, further studies are needed to demonstrate that the Framingham risk profile is useful in selecting persons who are likely to benefit and to determine the place of newer risk factors and that of early noninvasive detection of atheroma in the risk estimation–based treatment.
Attenuated Progression of Coronary Artery Disease After 6 Years of Multifactorial Risk Intervention
Authors: Niebauer Josef , Hambrecht Rainer , Velich Tamás , Hauer Klaus , Marburger Christian , Kälberer Barbara , Weiss Claus , von Hodenberg Eberhard , Schlierf Günter , Schuler Gerhard , Zimmermann Rainer , Kübler Wolfgang
Published: June 2012

Background
It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease. At the beginning of the study, 113 male patients with coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57); 90 patients (80%) could be reevaluated after 6 years.

Methods and Results
Patients in the intervention group (n=40) showed a reduction in total serum cholesterol (6.03±1.03 versus 5.67±1.01 mmol/L;
P
<.03) and triglyceride levels (1.94±0.8 versus 1.6±0.89 mmol/L;
P
<.005) and maintained their initial body mass index (26±2 versus 27±2 kg/m
2
;
P
=NS), but results were not statistically different from the control group (n=50) (total serum cholesterol, 6.05±1.02 versus 5.79±0.88 mmol/L; triglycerides, 2.25±1.28 versus 1.85±0.96 mmol/L [both
P
=NS]; body mass index, 26±2 versus 28±3 kg/m
2
[
P
<.0001]). In the intervention group, there was a significant 28% increase in physical work capacity (166±59 versus 212±89 W;
P
<.001), whereas values remained essentially unchanged in the control group (165±51 versus 170±60 W;
P
=NS; between groups,
P
<.05). In the intervention group, coronary stenoses progressed at a significantly slower rate than in the control group (
P
<.0001). Energy expenditure during exercise was assessed in a subgroup; patients with regression of coronary stenoses spent an average of 1784±384 kcal/wk (≈4 hours of moderate aerobic exercise per week). Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes.

Conclusions
After 6 years of multifactorial risk intervention, there is significant and persistent improvement in lipoprotein levels and physical work capacity, which results in a significant retardation of disease progression. These beneficial effects appear to be largely due to chronic physical exercise.
Hyperhomocyst(e)inemia Is a Risk Factor for Arterial Endothelial Dysfunction in Humans
Authors: Woo K.S. , Chook P. , Lolin Y.I. , Cheung A.S.P. , Chan L.T. , Sun Y.Y. , Sanderson J.E. , Metreweli C. , Celermajer D.S.
Published: June 2012

Background
Hyperhomocyst(e)inemia is associated with premature peripheral vascular, cerebrovascular, and coronary artery disease. Because homocysteine has been found to be damaging to endothelial cells in animal and cell culture studies, we evaluated the association between hyperhomocysteinemia and arterial endothelial dysfunction (a marker of early atherosclerosis) in asymptomatic adult subjects.

Methods and Results
Using high-resolution ultrasound, we measured endothelium-dependent flow-mediated dilation (EDD) and endothelium-independent nitroglycerin-induced dilation (GTN) of the brachial artery in 14 prospectively defined hyperhomocysteinemic (mean plasma homocysteine, 34.8±8.5 μmol/L), nonsmoking, healthy subjects aged 53±9 years and 14 control subjects with low plasma homocysteine levels (9.9±3.2 μmol/L). The two groups were well matched for age; sex; body mass index; blood pressure, blood cholesterol, folate, and vitamin B
12
levels; and vessel diameter. EDD was significantly lower in hyperhomocysteinemic subjects (6.5±1.7%) than in subjects with low homocysteine levels (10.8±1.7%) (
P
<.001). GTN responses were similar in the two subject groups (
P
=.90). Multivariate analysis confirmed homocysteine level as the strongest predictor for impaired EDD, independent of age, sex, body mass index, or blood pressure, folate, vitamin B
12
, and cholesterol levels.

Conclusions
Hyperhomocysteinemia is an independent risk factor for arterial endothelial dysfunction in healthy middle-aged adults.
Relationship Between Diabetes Mellitus and Long-term Survival After Coronary Bypass and Angioplasty
Authors: Barsness Gregory W. , Peterson Eric D. , Ohman E. Magnus , Nelson Charlotte L. , DeLong Elizabeth R. , Reves Joseph G. , Smith Peter K. , Anderson R. David , Jones Robert H. , Mark Daniel B. , Califf Robert M.
Published: June 2012

Background
Recent subgroup analyses of randomized trials have suggested that percutaneous intervention in diabetic patients with multivessel disease results in higher mortality than coronary artery bypass graft surgery (CABG). We studied the relationship between diabetes and survival after revascularization in a large prospective cohort of patients with multivessel coronary artery disease.

Methods and Results
By analyzing data for 3220 patients (24% diabetic) with symptomatic two- or three-vessel coronary disease who were undergoing percutaneous transluminal coronary angioplasty (PTCA) or CABG at Duke University Medical Center between 1984 and 1990, we found that at 5 years, unadjusted survival in the group of patients undergoing CABG was 74% in diabetics and 86% in nondiabetics. Similarly, 5-year survival among PTCA patients was 76% in diabetics and 88% in patients without diabetes. After adjustment for baseline characteristics, diabetic patients receiving either PTCA or CABG had significantly poorer survival than nondiabetics (χ
2
=43.56,
P
<.0001). Unlike previous studies, however, there was no significant differential effect of diabetes on outcome between patients treated with PTCA and those treated with CABG (χ
2
=0.01,
P
=.91).

Conclusions
Although diabetes was associated with a worse long-term outcome after both PTCA and CABG in patients with multivessel coronary artery disease, the effect of diabetes on prognosis was similar in both treatment groups. Thus, our findings support the concept that the choice of initial revascularization strategy should not be based exclusively on a history of diabetes but rather should rely on other factors, such as angiographic suitability and clinical status.
Predictive Value of Cardiac Troponin T in Pediatric Patients at Risk for Myocardial Injury
Authors: Lipshultz Steven E. , Rifai Nader , Sallan Stephen E. , Lipsitz Stuart R. , Dalton Virginia , Sacks David B. , Ottlinger Michael E.
Published: June 2012

Background
Biochemical markers have not been routinely used in children at risk for myocardial damage. Yet, because of somatic growth and the duration of survival, a low level of myocardial damage may ultimately be of more consequence in children than in adults.

Methods and Results
We investigated the utility of cardiac troponin T (cTnT) blood levels (CARDIAC T ELISA Troponin T, Boehringer Mannheim Corp) in 51 consecutively sampled patients from 1 day to 34 years of age (median=5.7 years) undergoing cardiovascular (n=19) or noncardiovascular (n=17) surgery or who received doxorubicin for acute lymphoblastic leukemia (ALL) (n=15). Minimum detectable cTnT elevations were 0.03 ng/mL. cTnT was measurable in children of all ages with myocyte damage. In patients who underwent cardiovascular surgery, a correlation was noted between a score of increasing surgical severity and the mean level of postoperative cTnT (
r
=.79,
P
<.0001). Postoperative cTnT levels were elevated in children who completed cardiovascular surgery with an open chest compared with those with a closed chest (
P
=.0083). In addition, cTnT levels before cardiovascular surgery predicted postoperative survival (
P
=.007). cTnT elevations were observed after initial doxorubicin therapy for ALL. The magnitude of elevation predicted left ventricular dilatation (
r
=.80 when variables were treated as continuous,
P
=.003) and wall thinning (
r
=.61,
P
=.044) 9 months later.

Conclusions
Elevations of blood cTnT in children relate to the severity of myocardial damage and predict subsequent subclinical and clinical cardiac morbidity and mortality.
Protective Effect of Chronic Garlic Intake on Elastic Properties of Aorta in the Elderly
Authors: Breithaupt-Grögler Kerstin , Ling Michael , Boudoulas Harisios , Belz Gustav G.
Published: June 2012

Background
Epidemiological studies have suggested that garlic may have protective effects against cardiovascular diseases. We undertook this cross-sectional observational study to test the hypothesis that regular garlic intake would delay the stiffening of the aorta relating to aging.

Methods and Results
We studied healthy adults (n=101; age, 50 to 80 years) who were taking ≥300 mg/d of standardized garlic powder for ≥2 years and 101 age- and sex-matched control subjects. Pulse wave velocity (PWV) and pressure-standardized elastic vascular resistance (EVR) were used to measure the elastic properties of the aorta. Blood pressures, heart rate, and plasma lipid levels were similar in the two groups. PWV (8.3±1.46 versus 9.8±2.45 m/s;
P
<.0001) and EVR (0.63±0.21 versus 0.9±0.44 m
2
· s
−2
· mm Hg
−1
;
P
<.0001) were lower in the garlic group than in the control group. PWV showed significant positive correlation with age (garlic group,
r
=.44; control group,
r
=.52) and systolic blood pressure (SBP) (garlic group,
r
=.48; control group,
r
=.54). With any degree of increase in age or SBP, PWV increased less in the garlic group than in the control group (
P
<.0001). ANCOVA and multiple regression analyses demonstrated that age and SBP were the most important determinants of PWV and that the effect of garlic on PWV was independent of confounding factors.

Conclusions
Chronic garlic powder intake attenuated age-related increases in aortic stiffness. These data strongly support the hypothesis that garlic intake had a protective effect on the elastic properties of the aorta related to aging in humans.
Inotropic Effects of Glyceryl Trinitrate and Spontaneous NO Donors in the Dog Heart
Authors: Preckel Benedikt , Kojda Georg , Schlack Wolfgang , Ebel Dirk , Kottenberg Karin , Noack Eike , Thämer Volker
Published: June 2012

Background
In vitro, NO has a biphasic effect on myocardial inotropy. To determine the inotropic effect of NO in vivo, we investigated the activity of glyceryl trinitrate (GTN) and the NO donors
S
-nitroso-
N
-acetyl-
d,l
-penicillamine (SNAP) and sodium-(2)-1-(
N
,
N
-diethyl-amino)-diazen-1-ium-1,2-diolat (DEA/NO) in dogs.

Methods and Results
Eight anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressures (tip manometers) and coronary flow (ultrasonic flow probes). Regional myocardial function was assessed by sonomicrometry as systolic wall thickening (sWT), mean systolic thickening velocity (V
s
), and regional myocardial stroke work index (RSW). GTN, SNAP, and DEA/NO were infused into the left anterior descending coronary artery (LAD) to achieve defined coronary plasma concentrations of GTN, SNAP (both 10 to 100 μmol/L), and DEA/NO (2 to 20 μmol/L). All drugs increased LAD flow and myocardial contractile function in the LAD-dependent myocardium within the first 120 seconds. The greatest inotropic effect was noted after infusion of DEA/NO (20 μmol/L), which increased sWT by 9.7±3.1% from 28.5±2.2%, V
s
by 10.3±3.4% from 9.1±1.1 mm/s, and RSW by 7.1±2.1% from 200.0±22.1 mm Hg×mm (
P
<.05). At the same time, systemic hemodynamics remained unchanged. Prevention of the flow response to GTN by external narrowing of the LAD did not influence the inotropic effect of GTN.

Conclusions
Organic nitrates and NO donors evoke a small but constant positive inotropic effect in vivo that is not caused by coronary vasodilation.
Electrophysiological Effects of Long, Linear Atrial Lesions Placed Under Intracardiac Ultrasound Guidance
Authors: Olgin Jeffrey E. , Kalman Jonathan M. , Chin Michael , Stillson Carol , Maguire Mark , Ursel Philip , Lesh Michael D.
Published: June 2012

Background
A curative atrial fibrillation procedure will most likely rely on creating transmural linear ablative lesions. However, it is currently unknown whether endocardial radiofrequency lesions can create lines of conduction block.

Methods and Results
In six pigs, intracardiac echocardiography was used to guide the positioning of multiple coil array catheters to bridge endocardial structures in three right atrial locations: (1) from the crista terminalis to the tricuspid annulus; (2) from the fossa ovalis to the crista terminalis; and (3) from the inferior vena cava to the tricuspid annulus. Once the catheter was positioned, linear lesions were made by radiofrequency energy applied sequentially to each of the four coils. After 15 days, the chest was opened and a 112-electrode epicardial plaque was positioned over the atrial free wall lesion to determine activation patterns. Three lesions were placed in each animal, with a mean procedure time of 47±11 minutes. Once adequate contact was determined by intracardiac echocardiography, a single series of radiofrequency application was required to achieve tissue heating (65±4°C) with a power of 21±10 W. Epicardial mapping demonstrated complete conduction block across the lesions in all animals, with split potentials and disparate activation times (64±16 ms) across the lesion. At autopsy, all lesions were discrete, continuous, and without evidence of charring. The lesions were within 0.3±0.5 mm of their targeted anatomic locations and measured 21±4 mm long and 2.8±0.6 mm wide. Histology revealed transmural fibrosis throughout the length of each lesion.

Conclusions
Linear lesions that are electrophysiologically transmural and continuous can be placed in the right atrium of normal pigs. With intracardiac echocardiography, adequate tissue contact over several coil electrodes can be ensured, resulting in short procedure times, efficient energy application, and accurate anatomically linked lesion placement.
Continuous Infusion of Prostacyclin Normalizes Plasma Markers of Endothelial Cell Injury and Platelet Aggregation in Primary Pulmonary Hypertension
Authors: Friedman Ronit , Mears J. Gregory , Barst Robyn J.
Published: June 2012

Background
Primary pulmonary hypertension (PPH) is characterized by vascular injury of pulmonary arterioles, in which endothelial dysfunction may play a major role. Although continuous infusion of prostacyclin (prostaglandin I
2
, a potent vasodilator released by vascular endothelial cells) improves the clinical status and survival in PPH, its mechanism or mechanisms of action remain unclear.

Methods and Results
We measured endothelium-derived clotting factors and assayed platelet aggregation in 64 patients (26 adults and 38 children) with PPH before long-term PGI
2
therapy. Repeat studies were performed in 42 patients (18 adults, 24 children) after one year of PGI
2
therapy. At baseline, 87% of adults and 79% of children had abnormal platelet aggregation. In addition, factor VIII, von Willebrand (vW) antigen, and ristocetin cofactor levels were abnormally high in 92%, 72%, and 52%, respectively, of the adults versus 29%, 16%, and 16%, respectively, of the children (
P
<.005 adults versus children). With long-term PGI
2
, platelet aggregation normalized in 83% of the adults and 80% of the children who had platelet aggregation abnormalities at baseline (
P
<.01). Factor VIII, vW antigen, and ristocetin cofactor also decreased with long-term PGI
2
in both groups (
P
<.02). The ratio of ristocetin cofactor to vW antigen, which may reflect biological activity of vW factor, increased with long-term PGI
2
in adults from an abnormally low level (0.6±0.2) to normal level (1.1±0.4), and in children the ratio increased from 0.8±0.3 to 1.3±0.4 (normal, 0.8 to 1.4).

Conclusions
Alterations in the coagulation system may contribute to the pathogenesis of PPH; the normalization of these endothelial markers concomitant with improvement in hemodynamic parameters with long-term PGI
2
suggests that long-term PGI
2
remodels the pulmonary vascular bed with subsequent decreases in endothelial cell injury and hypercoagulability.
Differences in HDL Cholesterol Concentrations in Japanese, American, and Australian Children
Authors: Dwyer Terence , Iwane Hisao , Dean Kimberlie , Odagiri Yuko , Shimomitsu Teruichi , Blizzard Leigh , Srinivasan Sathanur , Nicklas Theresa , Wattigney Wendy , Riley Malcolm , Berenson Gerald
Published: June 2012

Background
Mortality from coronary heart disease is relatively low in Japan compared with other developed countries and has remained low despite an increasing standard of living and an apparent increase in mean plasma cholesterol concentration in adults over the past three decades. Important differences in childhood plasma lipoprotein profile might contribute to some of the difference in coronary heart disease mortality seen between Japan and both Australia and North America.

Methods and Results
Plasma HDL cholesterol and total cholesterol were surveyed in representative populations of schoolchildren in Australia, Japan, and Bogalusa, La. The mean concentration of plasma HDL cholesterol (but not total cholesterol) was higher for Japanese schoolchildren than for Australian or US schoolchildren (
P
<.001). In addition, the difference in plasma HDL cholesterol between the ages of 8 to 10 years and 12 to 15 years was much greater for Australian (boys, 15.2%; girls, 2.6%) and US (boys, 9.1%; girls, 2.7%) children than for their Japanese counterparts (boys, 4.2%; girls, 1.9%). An examination of potential explanatory factors revealed little difference in body mass index between samples, higher physical activity levels for the Japanese compared with the Australians, and substantial differences in dietary intake between Japanese and Australian schoolchildren.

Conclusions
The relatively high ratio of plasma HDL cholesterol to total cholesterol in Japanese schoolchildren and the relatively small negative difference of plasma HDL cholesterol with age may help to explain why the coronary heart disease mortality rate in Japan is low compared with that in other developed countries.
Short-term Anti-Ischemic Effect of 17β-Estradiol in Postmenopausal Women With Coronary Artery Disease
Authors: Rosano Giuseppe M.C. , Caixeta Adriano Mendes , Chierchia Sergio , Arie Siguemituzo , Lopez-Hidalgo Miguel , Pereira Wagner I. , Leonardo Filippo , Webb Carolyn M. , Pileggi Fulvio , Collins Peter
Published: June 2012

Background
Short-term administration of 17β-estradiol improves effort-induced myocardial ischemia in female patients with coronary artery disease. 17β-Estradiol also has direct and indirect coronary vascular smooth muscle relaxing properties. The aim of the present study was to evaluate the effect of short-term administration of 17β-estradiol on pacing-induced myocardial ischemia by means of continuous monitoring of coronary sinus pH in 16 postmenopausal female patients with coronary artery disease.

Methods and Results
Patients underwent incremental atrial pacing starting at a rate of 100 bpm and increments of 20 bpm every 2 minutes up to 160 bpm before and 20 minutes after either 17β-estradiol (1 mg sublingual, 9 patients) or placebo (sublingual, 7 patients). The time to the onset of myocardial ischemia during pacing was significantly increased by 17β-estradiol (mean±SD, 254±36 versus 298±23 seconds;
P
<.02) but not by placebo (262±45 versus 256±34 seconds;
P
=NS) The pH shift was significantly reduced by 17β-estradiol but not by placebo at every step of the pacing protocol. The maximum pH shift at peak pacing was significantly reduced by the administration of 17β-estradiol by 0.022 pH units (95% CI, 0.001, 0.043;
P
<.04) but not by sublingual placebo (−0.002 pH units; 95% CI, −0.0073, 0.0021;
P
=NS). The maximum pH shift at maximum comparable pacing was also reduced by 17β-estradiol by 0.015 pH units (95% CI, 0.012, 0.017;
P
<.001) but not by placebo (−0.0022 pH units; 95% CI, −0.006, 0.0015;
P
=NS).

Conclusions
17β-Estradiol reduces the degree of pacing-induced myocardial ischemia in postmenopausal patients with coronary artery disease. The reduction of pacing-induced coronary sinus pH shift is consistent with an anti-ischemic effect of the hormone and is not due to preconditioning, as evidenced by the absence of improvement after placebo.
Effect of a Heart Failure Program on Hospitalization Frequency and Exercise Tolerance
Authors: Hanumanthu Sai , Butler Javed , Chomsky Don , Davis Stacy , Wilson John R.
Published: June 2012

Background
Most patients with heart failure are currently managed by physicians with little specific expertise in heart failure. This management system has been associated with evidence of suboptimal care, such as high rates of hospital readmission and underuse of ACE inhibitors. The current study was undertaken to determine whether hospitalization rates and functional outcomes are improved when patients are managed by physicians with special expertise in heart failure working in a dedicated heart failure program.

Methods and Results
All patients with heart failure referred to the Vanderbilt Heart Failure and Heart Transplantation Program between July 1994 and June 1995 were identified. Annual hospitalization rates, medications, and peak exercise capacity before and after referral were compared in patients followed for >30 days. A total of 187 patients were referred during the index time period, of whom 134 (72%) were followed for >30 days. During the year before referral, 94% of the patients were hospitalized (210 cardiovascular hospitalizations) versus 44% of the patients during the year after referral (104 hospitalizations) (53% reduction) (
P
<.01). Hospitalizations for heart failure decreased from 164 to 60 for all patients regardless of follow-up duration and decreased from 97 to 30 (69% reduction) for patients followed at least 1 year after referral. Eighty-eight of the patients were able to exercise at the time of referral. Peak exercise V̇
o
2
in this group increased from 12.8±4.7 to 15.7±4.8 mL · min
−1
· kg
−1
(
P
<.01) by 6 months after referral. Loop diuretic doses were on averaged doubled during the first 6 months after referral.

Conclusions
These findings suggest that patients with heart failure have fewer hospitalizations for heart failure and are significantly more functional when managed by heart failure specialists working in a dedicated heart failure program rather than by physicians with limited expertise in heart failure.
Multislice MRI in Assessment of Myocardial Perfusion in Patients With Single-Vessel Proximal Left Anterior Descending Coronary Artery Disease Before and After Revascularization
Authors: Lauerma Kirsi , Virtanen Kari S. , Sipilä Leena M. , Hekali Pauli , Aronen Hannu J.
Published: June 2012

Background
Our purpose was to use multislice MRI for detection of reversible myocardial ischemia and assessment of the effect of revascularization on tissue perfusion in patients with coronary artery disease.

Methods and Results
Eleven patients with single-vessel proximal left anterior descending coronary artery disease were studied with MRI and thallium scintigraphy before and 3 months after revascularization. All patients had a reversible perfusion defect by scintigraphy before treatment. With a 1.5-T MR imager, IR-prepared turboflash images were acquired in three left ventricular short-axis planes during 0.05 mmol/kg Gd-DTPA bolus at rest and with dipyridamole-induced stress. Before treatment, stress increased enhancement slope in normal (6.4±4.4 to 7.4±5.0 s
−1
,
P
<.04) and decreased it in underperfused (5.4±3.7 to 2.6±1.4 s
−1
,
P
<.02) regions, resulting in a contrast-to-noise ratio of 6.87±3.09 in underperfused myocardium. Revascularization normalized enhancement patterns of the formerly underperfused myocardium and decreased defect size both in scintigraphy (66±53° to 8±12°,
P
<.001) and MRI sections (49±41° to 9±8°,
P
<.001). Agreement of 85% in detection and correlation of 0.86 (SEE, 21°,
P
<.001) in sizing perfusion defects was found between MRI and scintigraphy.

Conclusions
Multislice contrast-enhanced MRI can be used to detect myocardial perfusion defects in patients with coronary artery disease and in assessment of the effect of treatment on myocardial perfusion.
Differential Effects of Anticoagulants on the Activation of Platelets Ex Vivo
Authors: Schneider David J. , Tracy Paula B. , Mann Kenneth G. , Sobel Burton E.
Published: June 2012

Background
Because activation of platelets and of the coagulation system are interdependent mediators of thrombosis, platelet activation was characterized in whole blood in the presence of anticoagulants used to assess platelet function in vitro or as treatment for patients with occlusive arterial disease.

Methods and Results
Blood was anticoagulated alone or in combination with citrate, ethylenediaminetetraacetatic acid, corn trypsin inhibitor (CTI, an inhibitor of activated factor XII), heparin, enoxaparin, recombinant tick anticoagulant peptide (rTAP), or recombinant hirudin. Platelet activation in response to adenosine diphosphate (ADP) or collagen was detected by assay of P-selectin on the platelet surface delineated by flow cytometry. Although minimal activation was seen without ADP, the fraction of platelets expressing P-selectin in response to ADP was greatest in blood anticoagulated with citrate compared with CTI and all other anticoagulants. ADP-induced platelet activation was greater in blood anticoagulated with heparin compared with an equipotent anti-Xa concentration of enoxaparin. More variable results were seen with collagen, but platelet activation in the presence of citrate was greater than that with CTI.

Conclusions
Interpretation of assays of inhibition of platelet activation by potentially therapeutic agents in vitro requires consideration of the effects of anticoagulants used. In addition, anticoagulants other than standard heparin may potentiate efficacy of antiplatelet drugs.
Dependency of Contractile Reserve on Myocardial Blood Flow
Authors: Lee Hans H. , Dávila-Román Victor G. , Ludbrook Philip A. , Courtois Michael , Walsh John F. , Delano Deborah A. , Rubin Patricia J. , Gropler Robert J.
Published: June 2012

Background
Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow.

Methods and Results
We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([
15
O]water) and oxygen consumption ([
11
C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve–positive, and 89 were dysfunctional and contractile reserve–negative. Myocardial blood flow at rest was lower in contractile reserve–negative (0.41±0.18 mL · g
−1
· min
−1
) than in contractile reserve–positive (0.50±0.22 mL · g
−1
· min
−1
) and normal segments (0.55±0.20 mL · g
−1
· min
−1
,
P
<.009). After dobutamine infusion, blood flow increased less in contractile reserve–negative (0.63±0.38 mL · g
−1
· min
−1
) than in contractile reserve–positive (1.28±0.65 mL · g
−1
· min
−1
) and normal segments (1.93±0.83 mL · g
−1
· min
−1
,
P
<.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve–negative (clearance rate of [
11
C]acetate, 0.043±0.012 min
−1
) than in contractile reserve–positive (0.048±0.01 min
−1
) and normal segments (0.058±0.008 min
−1
,
P
<.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve–negative (0.060±0.013 min
−1
) than in contractile reserve–positive (0.077±0.016 min
−1
) and normal segments (0.092±0.024 min
−1
,
P
<.0001). Of segments defined as viable by PET, 54% were contractile reserve–negative and exhibited lower blood flow with dobutamine (0.72±0.36 mL · g
−1
· min
−1
) than with viable, contractile reserve–positive segments (1.29±0.70 mL · g
−1
· min
−1
,
P
<.0001).

Conclusions
Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.
Association Between Serum Amyloid A Proteins and Coronary Artery Disease
Authors: Fyfe Alistair I. , Rothenberg L.S. , DeBeer Frederick C. , Cantor Rita M. , Rotter Jerome I. , Lusis Aldons J.
Published: June 2012

Background
Serum amyloid A (SAA) proteins are a family of inflammatory apolipoproteins that may modify high-density lipoprotein structure and function. Elevations of SAA have been reported in unstable coronary syndromes, but the levels and types of SAA protein in humans with spontaneous or transplant-associated coronary artery disease are not known.

Methods and Results
SAA levels were analyzed using an ELISA in 76 sera from 36 patients after cardiac transplantation and in 346 other individuals, 85 patients with atherosclerotic coronary disease plus 261 of their relatives. The mean SAA level was 5-fold higher in transplant patients (203±181 μg/mL [23 to 934 μg/mL]) compared with normal subjects without coronary disease (36±16 μg/mL [2.8 to 193 μg/mL],
P
<.005). The mean SAA level was significantly elevated in patients with transplant coronary disease (206±160 μg/mL, n=23) compared with those without (140±104 μg/mL, n=12,
P
=.02). Elevated SAA levels were associated with increased mortality after transplantation. On multiple regression analysis, SAA levels were predicted by corticosteroid dose, pretransplant diagnosis of atherosclerotic coronary artery disease, and the presence of transplant coronary disease. SAA levels were elevated in patients with spontaneous atherosclerotic coronary disease (49±31 μg/mL) compared with unaffected relatives (39±36 μg/mL, mean±SD,
P
=.02). There was no evidence for a genetic contribution to SAA levels. All inducible human SAA protein types were documented by immunoblotting in both spontaneous and transplant coronary disease.

Conclusions
Environmentally determined elevations in SAA levels in patients with both spontaneous and transplant coronary artery disease provide further evidence for a potential pathophysiological link between inflammation, lipoprotein metabolism, and the development of atherosclerosis.
ECG-Gated Three-dimensional Intravascular Ultrasound
Authors: von Birgelen Clemens , de Vrey Evelyn A. , Mintz Gary S. , Nicosia Antonino , Bruining Nico , Li Wenguang , Slager Cornelis J. , Roelandt Jos R. T. C. , Serruys Patrick W. , de Feyter Pim J.
Published: June 2012

Background
Automated systems for the quantitative analysis of three-dimensional (3D) sets of intravascular ultrasound (IVUS) images have been developed to reduce the time required to perform volumetric analyses; however, 3D image reconstruction by these nongated systems is frequently hampered by cyclic artifacts.

Methods and Results
We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9±1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3±1.5 side branches per segment. The minimum lumen CSA measured 6.4±1.7 mm
2
, and the maximum and average CSA plaque+media burden measured 60.5±10.2% and 46.5±9.9%, respectively. The automated contour-detection required 34.3±7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD<6.8%). Intraobserver and interobserver differences in area measurements (n=3421;
r
=.97 to.99) were <1.6% (SD<7.2%); intraobserver and interobserver differences in volumetric measurements (n=30;
r
=.99) were <0.4% (SD<3.2%).

Conclusions
ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time.
Prospective Prognostic Assessment of Blood Pressure Response During Exercise in Patients With Hypertrophic Cardiomyopathy
Authors: Sadoul Nicolas , Prasad Krishna , Elliott Perry M. , Bannerjee Soma , Frenneaux Michael P. , McKenna William J.
Published: June 2012

Background
Previous studies revealed that an abnormal blood pressure response (ABPR) during exercise was common in young hypertrophic cardiomyopathy (HCM) patients and was associated with a family history of premature sudden cardiac death (SCD). This study was performed prospectively to assess the prognostic significance of blood pressure response during exercise in young patients with HCM.

Methods and Results
Maximum symptom-limited treadmill exercise testing with continuous blood pressure monitoring was performed in 161 consecutive patients 8 to 40 years old (27±9). A normal blood pressure response, defined as an increase in the systolic pressure of at least 20 mm Hg from rest to peak exercise in the absence of a fall of >20 mm Hg from peak pressure, was seen in 101 (63%). In 60 (37%), the blood pressure response was abnormal. There was no significant difference in patients with normal blood pressure response and ABPR in terms of age, sex, follow-up, or recognized risk factors for SCD. During the follow-up period (mean, 44±20 months), SCD occurred in 12 patients: 3 (3%) in the normal blood pressure response group versus 9 (15%) in the ABPR group (
P
<.009). ABPR had a sensitivity of 75%, a specificity of 66%, a negative predictive value of 97%, and a positive predictive value of 15% for the prediction of SCD. There was no significant difference in the incidence of other recognized risk factors between patients with SCD and the survivors.

Conclusions
A normal exercise blood pressure response identifies low-risk young patients with HCM. An ABPR identifies the high-risk cohort; the low positive predictive accuracy, however, indicates that further risk stratification is warranted.