bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal Awake Respiratory Patterns Are Common in Chronic Heart Failure and May Prevent Evaluation of Autonomic Tone by Measures of Heart Rate Variability
Authors: Mortara Andrea , Sleight Peter , Pinna Gian Domenico , Maestri Roberto , Prpa Alexander , La Rovere Maria Teresa , Cobelli Franco , Tavazzi Luigi
Published: June 2012

Background
Reduced heart rate variability, particularly in the very-low-frequency (VLF) spectral band, has been found to be a marker for poor prognosis in patients after myocardial infarction, but the origin of the VLF oscillations is unclear. In this study, we demonstrate that the power of cardiovascular oscillations in the VLF band in awake patients with mild to severe chronic heart failure is greatly increased by the common occurrence of unrecognized irregularity of breathing, which may confound the use of heart rate variability measures as indexes of autonomic tone or prognosis.

Methods and Results
Among 110 consecutive patients referred for consideration of transplantation, 90 were in sinus rhythm, of whom 10 were excluded as unstable. The remaining 80 patients underwent recordings of ECG, beat-to-beat arterial oxygen saturation (Sa
o
2
), and respiration during both spontaneous and controlled breathing. During spontaneous awake breathing, 64% showed periodic breathing or Cheyne-Stokes respiration (CSR), which was associated with dominant power in the VLF band of all signals. This VLF power accounted for 55%, 77%, and 87% of heart rate variability, respectively, in patients with normal breathing, periodic breathing, and CSR. It was reduced by 48% and 62%, respectively, during controlled breathing in patients with periodic breathing or CSR. Controlled ventilation also improved oxygen saturation and markedly reduced its variability.

Conclusions
Breathing disorders are surprisingly common in awake patients with poor left ventricular function and produce large VLF oscillations in heart rate variability. If measures of heart rate variability are used for prognostic purposes during both short-term and long-term recordings, the confounding effects of variable respiratory patterns should be excluded. Respiratory rehabilitation might help control potentially hazardous surges in sympathetic tone.
Glucocorticoid Receptor Regulates Expression of L-Selectin and CD11/CD18 on Human Neutrophils
Authors: Filep János G. , Delalandre Aline , Payette Yves , Földes-Filep Éva
Published: June 2012

Background
Recent studies have raised the hypothesis that glucocorticoids could diminish the ability of endothelial cells to direct leukocyte traffic into inflamed tissues by inhibiting expression of the adhesion molecules endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. The aim of the present study was to investigate whether glucocorticoids also regulate the expression of L-selectin and CD11/CD18 integrins on human neutrophil granulocytes.

Methods and Results
Incubation of human whole blood with platelet-activating factor (PAF, 1 μmol/L) evoked downregulation of L-selectin and upregulation of CD11/CD18 adhesion receptors on neutrophils as measured by flow cytometry. While dexamethasone (0.1 nmol/L to 100 μmol/L) did not affect expression of adhesion molecules on resting neutrophils, it attenuated the PAF-induced changes in L-selectin and CD18 expression in a time- and concentration-dependent fashion with IC
50
values of 31 and 13 nmol/L, respectively. These effects of dexamethasone were completely aborted by RU-486 (10 μmol/L), which blocks transcriptional activation of the glucocorticoid receptor, and by the protein synthesis inhibitor cycloheximide (35.5 μmol/L). Dexamethasone, up to a concentration of 1 μmol/L, neither affected significantly the release of granule enzymes nor interfered with PAF binding to its membrane receptors.

Conclusions
Our results show that glucocorticoids at clinically relevant concentrations exert specific actions on expression of adhesion molecules on activated neutrophils, which are mediated through ligation of glucocorticoid receptors and induction of protein synthesis, and suggest a novel mechanism by which anti-inflammatory corticosteroids may inhibit leukocyte accumulation.
Prevention of Bacterial Endocarditis
Authors: Dajani Adnan S. , Taubert Kathryn A. , Wilson Walter , Bolger Ann F. , Bayer Arnold , Ferrieri Patricia , Gewitz Michael H. , Shulman Stanford T. , Nouri Soraya , Newburger Jane W. , Hutto Cecilia , Pallasch Thomas J. , Gage Tommy W. , Levison Matthew E. , Peter Georges , Zuccaro Gregory
Published: June 2012

Objective
To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease.

Participants
An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy.

Evidence
The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words
endocarditis, bacteremia,
and
antibiotic prophylaxis.
Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence.

Consensus Process
The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment.

Conclusions
Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.
Total, LDL, and HDL Cholesterol Decrease With Age in Older Men and Women
Authors: Ferrara Assiamira , Barrett-Connor Elizabeth , Shan Jun
Published: June 2012

Background
The purpose of the present study was to study the effects of age, weight change, and covariates on lipid and lipoprotein levels cross-sectionally and prospectively in an elderly population.

Methods and Results
A community-based sample of 1041 men and 1303 women aged 50 to 93 years was studied cross-sectionally in 1984 to 1987, with follow-up of 372 men and 545 women 8 years later. In the cross-sectional study, levels of total cholesterol (TC) and LDL cholesterol (LDL-C) decreased and levels of HDL cholesterol (HDLC) increased with age in men (all
P
<.001) but not in women. In the prospective study, TC, LDL-C, and HDL-C levels all decreased in both men and women, in all age groups (50 to 64 years, 65 to 74 years, and ≥75 years) and in all weight change groups (>2.5-kg loss, change within 2.5 kg, and >2.5-kg gain) and in all waist girth change groups, for an overall decrement of ≈1% per year. In multiple linear regression models, change in weight was the most important independent and consistent predictor of changes in TC, LDL-C, and HDL-C. Similar results were obtained in analyses excluding subjects taking lipid-lowering drugs or estrogen and in analyses adjusted for changes in cigarette smoking, alcohol intake, physical activity, medication use, and incident myocardial infarction, cancer, or diabetes.

Conclusions
Cross-sectional decrements in TC and LDL-C with age in men are not explained by survivor bias because they are also observed prospectively. Although weight change was the most important explanatory variable, TC, LDL-C, and HDL-C levels also decreased in those who lost or gained weight. Age was not an independent predictor of change. Other prospective studies are recommended to better define the causes and consequences of cholesterol and lipoprotein changes in old age.
Intermittent Claudication
Authors: Murabito Joanne M. , D’Agostino Ralph B. , Silbershatz Halit , Wilson Peter W. F.
Published: June 2012

Background
Intermittent claudication identifies persons at increased risk for death and disability.

Methods and Results
Using 38-year follow-up data for the original cohort in the Framingham Heart Study, we developed an intermittent claudication risk profile. Intermittent claudication occurred in a total of 381 men and women. Age, sex, serum cholesterol, hypertension, cigarette smoking, diabetes, and coronary heart disease were associated with an increased risk for claudication and were included in the profile. A pooled logistic regression model was used to compute the probability of intermittent claudication for specified levels of risk factors.

Conclusions
The intermittent claudication risk profile allows physicians to identify high-risk individuals during a routine office visit and can be used to educate patients about modifiable risk factors, particularly smoking and blood pressure. Improved compliance with risk factor modification strategies may result in a beneficial impact on survival.
Comparison of Low-Molecular-Weight Heparin With Unfractionated Heparin Acutely and With Placebo for 6 Weeks in the Management of Unstable Coronary Artery Disease
Authors: Klein Werner , Buchwald Arnd , Hillis Stuart E. , Monrad Scott , Sanz Ginés , Turpie A. Graham G. , van der Meer Jan , Olaisson Eric , Undeland Sven , Ludwig Karin
Published: June 2012

Background
Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease.

Method and Results
Patients with unstable angina or non–Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 IU/kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 IU once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin-treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively.

Conclusions
Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non–Q-wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.
Redifferentiation of Smooth Muscle Cells After Coronary Angioplasty Determined via Myosin Heavy Chain Expression
Authors: Aikawa Masanori , Sakomura Yasunari , Ueda Makiko , Kimura Kenjiro , Manabe Ichiro , Ishiwata Sugao , Komiyama Nobuyuki , Yamaguchi Hiroshi , Yazaki Yoshio , Nagai Ryozo
Published: June 2012

Background
The pathophysiology of phenotypic modulation of smooth muscle cells (SMCs) involved in restenosis after angioplasty is not well understood. Smooth muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs. SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated in immature or activated SMC.

Methods and Results
To determine SMC phenotypes in neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA), we performed immunohistochemistry on human coronary arteries with antibodies against α-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six autopsied patients and from atherectomy specimens from 16 patients who had undergone PTCA. Medial SMCs were positive for α-actin, SM1, and SM2. Expression of SM1 and SM2 in the neointima varied with the time after intervention, whereas α-actin was constitutively expressed in all cases studied. Neointimal cells at 16 and 20 days after PTCA contained α-actin but little or no SM1 or SM2, indicating that these cells modulated their phenotype to the immature state. Neointimal SMCs recovered SM MHC expression, first SM1 and then SM2, by 6 months after PTCA. Increased expression of SMemb was found in the neointima but without apparent relationship to the time after PTCA.

Conclusions
Neointimal SMCs show features of an undifferentiated state, indicated by altered expression of SM MHC, and undergo redifferentiation in a time-dependent manner. The expression of SM MHC isoforms provides insight into the biology of healing after angioplasty and furnishes useful tools for the understanding of the roles of differentiation and phenotypic modulation of SMCs in human vascular lesions.
Randomized Comparison of Angioplasty of Complex Coronary Lesions at a Single Center
Authors: Reifart Nicolaus , Vandormael Michel , Krajcar Mladen , Göhring Stefan , Preusler Wolfgang , Schwarz Franz , Störger Hans , Hofmann Manfred , Klöpper Johann , Müller Stefan , Haase Jürgen
Published: June 2012

Background
The purpose of this study was to test whether coronary revascularization with ablation of either excimer laser or rotational atherectomy can improve the initial angiographic and clinical outcomes compared with dilatation (balloon angioplasty) alone.

Methods and Results
At a single center, a total of 685 patients with symptomatic coronary disease warranting elective percutaneous revascularization for a complex lesion were randomly assigned to balloon angioplasty (n=222), excimer laser angioplasty (n=232), or rotational atherectomy (n=231). The primary end point was procedural success (diameter stenosis <50%, absence of death, Q-wave myocardial infarction, or coronary artery bypass surgery). The patients who underwent rotational atherectomy had a higher rate of procedural success than those who underwent excimer laser angioplasty or conventional balloon angioplasty (89% versus 77% and 80%,
P=
.0019), but no difference was observed in major in-hospital complications (3.2% versus 4.3% versus 3.1%,
P=
.71). At the 6-month follow-up, revascularization of the original target lesion was performed more frequently in the rotational atherectomy group (42.4%) and the excimer laser group (46.0%) than in the angioplasty group (31.9%,
P=
.013).

Conclusions
Procedural success of rotational atherectomy is superior to laser angioplasty and balloon angioplasty; however, it does not result in better late outcomes. The role of plaque debulking before balloon dilatation in percutaneous coronary revascularization remains to be fully defined.
Impact of Respiratory Maneuvers on Cardiac Volume Within Left-Breast Radiation Portals
Authors: Chen Ming Hui , Chuang Michael L. , Bornstein Bruce A. , Gelman Rebecca , Harris Jay R. , Manning Warren J.
Published: June 2012

Background
Late cardiac morbidity and mortality have been reported among left-breast cancer survivors treated with radiation therapy. Radiation-induced cardiotoxicity is affected by the volume of myocardium included in the radiation portals. We hypothesize that simple respiratory maneuvers may alter the position of the heart relative to the portals without altering the radiation dose delivered to the breast.

Methods and Results
Fourteen healthy female adult volunteers underwent cardiac MRI to determine the cardiac volume included in the typical left-breast radiation field during respiratory maneuvers. Cardiac volume within the radiation portals was assessed from a transverse stack of 14 1-cm-thick contiguous slices covering the entire heart, obtained during breath holding at end-tidal volume (baseline), deep inspiration, and forced expiration. Thirteen subjects (92%) had inclusion of a portion of the heart within the radiation portals at end-tidal volume (median, 20.9 cm
3
; range, 1.3 to 88.4 cm
3
). In these subjects, inspiration decreased the cardiac volume included within the radiation portals (median change: −10.7 cm
3
[−40.2%],
P
<.001 versus end-tidal volume), whereas expiration increased the cardiac volume included (median change: 4.0 cm
3
[21.5%];
P
<.001 versus end-tidal volume).

Conclusions
Inclusion of a portion of the heart in the left-breast radiation field is common. The use of simple inspiratory maneuvers significantly decreases cardiac volume within the radiation portals. Such an approach during delivery of radiation therapy may allow for preservation of radiation dosage to the breast while reducing cardiac involvement and subsequent mortality.
Albumin Excretion Rate Increases During Acute Myocardial Infarction and Strongly Predicts Early Mortality
Authors: Berton Giuseppe , Citro Tiziana , Palmieri Rosa , Petucco Stefania , Renzo De Toni  , Palatini Paolo
Published: June 2012

Background
This study was undertaken to assess whether albumin excretion rate (AER) increases during acute myocardial infarction (AMI) and whether it predicts in-hospital mortality.

Methods and Results
The study was carried out in 496 subjects admitted to hospital for suspected AMI. Of these, 360 had evidence of AMI. The other 136 were studied as control subjects. AER was assessed by radioimmunoassay in three 24-hour urine collections performed on the first, third, and seventh days after admission. Left ventricular ejection fraction was measured by two-dimensional echocardiography in 254 subjects. AER adjusted for several confounders was higher in the AMI than the non-AMI group on the first (69.2±5.2 versus 27.3±8.5 mg/24 h,
P
<.0001) and third (30.3±2.7 versus 12.5±4.4 mg/24 h,
P
=.001) days, whereas no difference was present on the seventh day. When the subjects with heart failure were excluded, the difference between the two groups remained significant (first day,
P
<.0001; third day,
P
=.001). On the basis of classification of the 26 AMI patients who died in hospital according to whether they had normal AER, microalbuminuria, or overt albuminuria, mortality rate progressively increased with increasing levels of AER (
P
<.0001). In a Cox’s proportional hazards model, AER was a better predictor of in-hospital mortality than Killip class or echocardiographic left ventricular ejection fraction. A cutoff value of 50 mg/24 h for first-day AER and 30 mg/24 h for third-day AER yielded a sensitivity of 92.3% and of 88.5% and a specificity of 72.4% and of 79.3%, respectively, for mortality. Adjusted relative risks for the two cutoff values were 17.3 (confidence limits, 4.6 to 112.7) and 8.4 (confidence limits, 2.4 to 39.3), respectively.

Conclusions
These data show that AER increases during AMI and that it yields prognostic information additional to that provided by clinical or echocardiographic evaluation of left ventricular performance.
Effects of Dobutamine at Maximally Tolerated Dose on Myocardial Blood Flow in Humans With Ischemic Heart Disease
Authors: Skopicki Hal A. , Abraham Stephen A. , Picard Michael H. , Alpert Nathaniel M. , Fischman Alan J. , Gewirtz Henry
Published: June 2012

Background
This study tests the hypothesis in humans with ischemic heart disease that myocardial blood flow response to dobutamine is linearly correlated with blood flow response to adenosine.

Methods and Results
PET with [
13
N]ammonia was used to measure myocardial blood flow at rest and during adenosine and dobutamine at the maximally tolerated dose. Myocardial segments were defined physiologically on the basis of blood flow response to adenosine: normal, ≥2 mL · min
−1
· g
−1
; abnormal, <2 mL · min
−1
· g
−1
; and “steal,” decline versus baseline ≥0.15 mL · min
−1
· g
−1
. The patient population consisted of 11 men and 2 women. Dobutamine increased heart rate (79±22 to 115±28 bpm) and rate-pressure product (9748±2862 to 15 157±3433 mm Hg/min) significantly (both
P
<.01). Myocardial blood flow at rest in abnormal segments (0.50±0.23 mL · min
−1
· g
−1
) was reduced (
P
<.001) versus normal (0.90±0.45) and steal (0.92±0.60). Nevertheless, in abnormal segments, blood flow increased versus rest (
P
<.001) with dobutamine (0.83±0.43) and adenosine (0.90±0.49). In steal segments, myocardial blood flow declined versus baseline (
P
<.001) with dobutamine (0.68±0.46) and adenosine (0.50±0.45). In normal segments, myocardial blood flow increased (
P
<.001) with dobutamine (2.16±0.99) and adenosine (3.10±0.90). Over the range of flows, the correlation between adenosine and dobutamine was good (
r
=.78,
P
<.0001). Although flow with dobutamine in normal segments correlated with rate-pressure product (
r
=.81,
P
<.05), the slope of the line was 2.7±0.8 (
P
<.02), and normalized blood flow (3.3±2.5 ×rest) exceeded normalized rate-pressure product (1.9±0.8 ×rest;
P
<.05).

Conclusions
In humans with ischemic heart disease, myocardial blood flow responses to dobutamine and adenosine are linearly correlated over a wide range. The hyperemic response to dobutamine is in excess of that predicted by rate-pressure product and reflects the unmeasured inotropic, oxygen-wasting, and β
2
-agonist effects of the drug. Dobutamine induces coronary steal with a frequency approaching that of adenosine.
Endothelium-Dependent Dilatation Is Impaired in Young Healthy Subjects With a Family History of Premature Coronary Disease
Authors: Clarkson Peter , Celermajer David S. , Powe Amanda J. , Donald Ann E. , Henry Ronald M. A. , Deanfield John E.
Published: June 2012

Background
A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk factor for coronary disease. Both genetic and environmental influences are likely to be responsible and may interact, but their relative importance is unclear.

Methods and Results
We studied endothelial function in 50 first-degree relatives (31 men, 19 women; mean age, 25±8 years) of patients (men ≤45years, women ≤55years) with proven CAD. All subjects were well, lifelong nonsmokers, not diabetic, and not hypertensive and took no medications. Using high-resolution external vascular ultrasound, we measured brachial artery diameter at rest and in response to reactive hyperemia (with increased flow causing an endothelium-dependent vasodilatation) and to sublingual glyceryltrinitrate (GTN, an endothelium-independent dilator). Vascular responses were compared with those of 50 healthy control subjects matched for age and sex. Flow-mediated dilatation (FMD) was impaired in the family history group (4.9±4.6% versus 8.3±3.5% in control subjects,
P
<.005). In contrast, GTN caused dilatation in all subjects (family history, 17.1±8.8%; control subjects, 19.0±6.3%;
P
=NS), suggesting that reduced FMD was due to endothelial dysfunction. When the family history subjects were subdivided, those found to have a serum cholesterol >4.2 mmol/L (group A, n=10) had mildly impaired FMD compared with control subjects (5.5±5.1% versus 8.3±3.5%). In others whose affected relative had coronary risk factors (group B, n=24), FMD was also only slightly reduced (6.2±4.8% versus 8.3±3.5%). In contrast, subjects with no risk factors and whose affected relative had a normal cardiovascular risk factor profile (group C, n=16) had markedly impaired FMD (2.9±3.7% versus 8.3±3.5%). Although ANOVA of the three family history subgroups did not reach statistical significance (F=2.55,
P
=.09), pairwise analysis showed that FMD in group C was significantly impaired compared with group B (
P
=.026).

Conclusions
Healthy young adults with a family history of premature coronary disease may have impaired endothelium-dependent dilatation, even in the absence of other cardiovascular risk factors. Those subjects, who were free of risk factors and whose affected first-degree relative was free of risk factors, had the most impaired endothelial function, suggesting a genetic influence on early arterial physiology that may be relevant to later clinical disease.
Effect of Nadroparin, a Low-Molecular-Weight Heparin, on Clinical and Angiographic Restenosis After Coronary Balloon Angioplasty
Authors: Lablanche Jean-Marc , McFadden Eugène P. , Meneveau Nicolas , Lusson Jean René , Bertrand Bernard , Metzger Jean-Philippe , Legrand Victor , Grollier Gilles , Macaya Carlos , de Bruyne Bernard , Vahanian Alec , Grentzinger Alain , Masquet Christiane , Wolf Jean-Eric , Tobelem Gerard , Fontecave Sylvie , Vacheron André , d’Azemar Pascal , Bertrand Michel E.
Published: June 2012

Background
Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty.

Methods and Results
In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10 250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37±0.66 mm, 51.9±21.0%) did not differ from the corresponding values in the control group (1.48±0.59 mm, 48.8±18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%).

Conclusions
Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.
Aortic Valve Replacement in Patients 80 Years of Age and Older
Authors: Asimakopoulos George , Edwards Maria-Benedicta , Taylor Kenneth M.
Published: June 2012

Background
Aging of the population and advances in preoperative and postoperative care are reflected in an increasing number of patients ≥80 years of age undergoing aortic valve replacement (AVR) in the United Kingdom. The present study presents data on postoperative 30-day mortality, actuarial survival, and cause of death based on a large collective patient population.

Methods and Results
Data were extracted from the UK Heart Valve Registry. From January 1986 to December 1995, 1100 patients ≥80 years of age underwent AVR and were reported to the registry. Six hundred eleven patients (55.5%) were women. The mean follow-up time was 38.9 months. The 30-day mortality was 6.6%. Of the 73 early deaths, 42 were due to cardiac reasons. The actuarial survival was 89%, 79.3%, 68.7%, and 45.8% at 1, 3, 5, and 8 years, respectively. After the first 30 postoperative days, 144 of the 205 deaths were due to noncardiac reasons. Malignancy, stroke, and pneumonia were the most common causes of late death. Bioprosthetic valves were implanted in 969 patients (88%) and mechanical valves in 131 (12%) patients. There was no difference in early mortality and actuarial survival between the two groups (
P
>.05).

Conclusions
The above results suggest that under the selection criteria for AVR currently applied in the United Kingdom, patients ≥80 years of age show a satisfactory early postoperative outcome and moderate medium-term survival benefit.
Left Ventricular Contractile Effects of Inducible Nitric Oxide Synthase in the Human Allograft
Authors: Paulus Walter J. , Kästner Stefanie , Pujadas Pénélope , Shah Ajay M. , Drexler Helmut , Vanderheyden Marc
Published: June 2012

Background
Myocardial expression of inducible (i) nitric oxide (NO) synthase (iNOS) gene has been reported in transplant recipients and in dilated cardiomyopathy. NO derived from NO donor or from coronary endothelium has previously been shown in the human heart to reduce end-systolic left ventricular (LV) pressure, especially during β-adrenoreceptor stimulation, because of earlier onset of LV relaxation. The present study investigated in transplant recipients whether a similar cardiodepressant effect could be attributed to NO derived from iNOS.

Methods and Results
In 16 transplant recipients who were free of rejection or graft vasculopathy, microtip LV pressure recordings, LV angiograms, and endomyocardial biopsies were obtained at annual coronary angiography. In 8 transplant recipients, microtip LV pressure recordings were obtained during intravenous dobutamine(5 μg · kg
−1
· min
−1
). Competitive reverse transcription–polymerase chain reaction of iNOS mRNA was performed on the endomyocardial biopsies, and the intensity of iNOS mRNA expression was quantified on a scale ranging from 0 to 5+. All measures of baseline LV function were comparable in transplant recipients with low (≤2+) or high myocardial iNOS mRNA. During intravenous dobutamine infusion, there was a significant correlation between the abbreviation of LV electromechanical systole time (LVEST is the time from onset of QRS to dP/dt
min
) and the rise of LV dP/dt
max
(
r
=.79;
P
<.02). By use of a multiple regression analysis, addition of the intensity of iNOS mRNA expression as an independent variable significantly (
P
<.005) improved the correlation between ΔLVEST and ΔLV dP/dt
max
(
P
<.001;
r
=.97), implying a larger abbreviation of LV contraction for a similar rise in LV dP/dt
max
, when myocardial iNOS mRNA was higher. The larger abbreviation of LV contraction in-patients with high iNOS mRNA was associated with a decrease in LV end-systolic pressure (−31±16 mm Hg).

Conclusions
Myocardial iNOS gene expression in the human allograft influences the LV contractile response to β-adrenergic stimulation through earlier onset of LV relaxation and reduction of LV end-systolic pressure. These effects are similar to the LV contractile effects of NO derived from NO donor or from coronary endothelium.
Arterial Baroreflex Modulation of Heart Rate in Chronic Heart Failure
Authors: Mortara Andrea , La Rovere Maria Teresa , Pinna Gian Domenico , Prpa Alexander , Maestri Roberto , Febo Oreste , Pozzoli Massimo , Opasich Cristina , Tavazzi Luigi
Published: June 2012

Background
In chronic heart failure (CHF), arterial baroreflex regulation of cardiac function is impaired, leading to a reduction in the tonic restraining influence on the sympathetic nervous system. Because baroreflex sensitivity (BRS), as assessed by the phenylephrine technique, significantly contributes to postinfarction risk stratification, the aim of the present study was to evaluate whether in CHF patients a depressed BRS is associated with a worse clinical hemodynamic status and unfavorable outcome.

Methods and Results
BRS was assessed in 282 CHF patients in sinus rhythm receiving stable medical therapy (age, 52±9 years; New York Heart Association [NYHA] class, 2.4±0.6; left ventricular ejection fraction [LVEF], 23±6%). The BRS of the entire population averaged 3.9±4.0 ms/mm Hg (mean±SD) and was significantly related to LVEF and hemodynamic parameters (LVEF,
P
<.005; cardiac index and pulmonary wedge pressure,
P
<.001 by regression analysis). Patients in NYHA classes III or IV and those with severe mitral regurgitation had markedly depressed vagal reflexes. The association of BRS with survival was described after its categorization in three groups: below the lowest quartile (<1.3 ms/mm Hg), between the lowest quartile and the median (1.3 to 3 ms/mm Hg), and above the median (>3 ms/mm Hg). During a mean follow-up of 15±12 months, 78 primary events (cardiac death, nonfatal cardiac arrest, and status 1 priority transplantation) occurred (27.6%). BRS was significantly related to outcome (log rank, 9.1;
P
<.01), with a relative risk of 2.7 (95% confidence interval, 1.6 to 4.7) for patients with the major derangement in BRS (<1.3 ms/mm Hg). At multivariate analysis, BRS was an independent predictor of death after adjustment for noninvasive known risk factors but not when hemodynamic indexes were also considered. In CHF patients with severe mitral regurgitation, however, BRS remained a strong prognostic marker independent of hemodynamic function.

Conclusions
In moderate to severe CHF, a depressed sensitivity of vagal reflexes parallels the deterioration of clinical and hemodynamic status and is significantly associated with poor survival. Particularly in patients with severe mitral regurgitation the baroreceptor modulation of heart rate provides prognostic information of incremental value to hemodynamic parameters.
Instant Power Spectrum Analysis of Heart Rate Variability During Orthostatic Tilt Using a Time-/Frequency-Domain Method
Authors: Jasson Sylvain , Médigue Claire , Maison-Blanche Pierre , Montano Nicola , Meyer Laurent , Vermeiren Christophe , Mansier Pascale , Coumel Philippe , Malliani Alberto , Swynghedauw Bernard
Published: June 2012

Background
Spectral analysis of heart rate (HR) variability (HRV) requires, as a rule, some level of stationarity and, as a result, is inadequate to quantify biological transients. A time-/frequency-domain method (TF) was developed to obtain an instant spectral power (SP) of HRV during tilt.

Methods and Results
HR was recorded by Holter monitoring in volunteers and analyzed with a TF, the smoothed pseudo–Wigner-Ville transformation (SPWVT), with the table inclination randomly set or continuously increased while the table rotated in head-up position. (1) The SPWVT assesses, beat by beat, the instant center frequency (ICF) of the SP. ICF correlates better with instant HR than the ratio of low- (LF) to high-frequency (HF) oscillations. The transient effect of tilt is better characterized as a shift of SP toward lower frequencies than by changes in amplitudes. (2) The method evidences variations of HR from one second to another. During the passage to head-up position, the vagal withdrawal and the sympathetic activation occur nearly simultaneously, as indicated by the instant changes in both LF and HF amplitudes and ICF. (3) The averaged results of the SPWVT give results similar to those previously obtained with autoregressive algorithms.

Conclusions
The SPWVT is a new tool to explore HR transitions such as periods before episodes of arrhythmias on a time scale of one beat and allows quantification of an instant frequency index (ICF) that closely reflects the instantaneous relationship between sympathetic and vagal modulations.
Cell-Derived Microparticles Generated in Patients During Cardiopulmonary Bypass Are Highly Procoagulant
Authors: Nieuwland Rienk , Berckmans René J. , Rotteveel-Eijkman Reni C. , Maquelin Kyra N. , Roozendaal Klaas J. , Jansen Piet G. M. , Have Klaas ten , Eijsman León , Hack C. Erik , Sturk Augueste
Published: June 2012

Background
Microparticles from platelets and other cells have been extensively studied and characterized in vitro. Although the level of platelet-derived microparticles is elevated in a variety of diseases, including cardiac surgery, virtually nothing is known about their functions in vivo. The aim of the present study was to investigate the procoagulant properties of microparticles generated in vivo.

Methods and Results
In 6 patients at the end of cardiopulmonary bypass, 14.8×10
9
/L (median; range, 9.7 to 27.4×10
9
/L) platelet-derived microparticles were present in pericardial blood, whereas blood obtained from the systemic circulation contained 1.6×10
9
/L (median; range, 0.4 to 8.9×10
9
/L) of such microparticles, as determined by flow cytometry. Microparticles stained positively for phosphatidylserine as determined with labeled annexin V. In contrast to systemic blood, pericardial blood contained not only microparticles of platelet origin but also microparticles that originated from erythrocytes, monocytes, or granulocytes, and other hitherto unknown cellular sources. Plasma prepared from pericardial blood and to a lesser extent plasma from systemic blood obtained at the same time, stimulated formation of thrombin in vitro. This activity of pericardial plasma was lost after removal of its microparticles by high-speed centrifugation, whereas the corresponding microparticle pellet was strongly procoagulant. The generation of thrombin in vitro involved a tissue factor/factor VII–dependent and factor XII–independent pathway.

Conclusions
This study is the first to demonstrate that microparticles generated in vivo can stimulate coagulation.
Differential Effect of Hydrogen Peroxide and Superoxide Anion on Apoptosis and Proliferation of Vascular Smooth Muscle Cells
Authors: Li Pei-Feng , Dietz Rainer , von Harsdorf Rüdiger
Published: June 2012

Background
Proliferation and apoptosis of vascular smooth muscle cells (VSMCs) are two important components of atherosclerosis, restenosis, and hypertension. Although reactive oxygen species have been demonstrated to participate in the pathogenesis of these diseases, their precise involvement has not been fully understood. We hypothesized that different reactive oxygen species exert distinct effects on proliferation and apoptosis of VSMCs.

Methods and Results
Cultured rat VSMCs were exposed to xanthine oxidase/xanthine (XO/X) or H
2
O
2
-Fe(II). A single exposure to XO/X predominantly resulted in cell proliferation, whereas frequent exposures to high levels of XO/X predominantly resulted in cell death. Administration of superoxide dismutase and catalase revealed that O
2
−
but not H
2
O
2
was mitogenic to VSMCs, whereas H
2
O
2
was responsible for VSMC death. Treatment with H
2
O
2
-Fe(II) alone or in the presence of different hydroxyl radical scavengers showed that VSMC death occurred in a dose-dependent manner and was mediated by the formation of hydroxyl radicals. Cell death caused by XO/X or H
2
O
2
-Fe(II) occurred by apoptosis as revealed by condensation of nuclei, appearance of a “DNA ladder,” increases in DNA fragmentation, and positive in situ nick-end labeling. Northern blot analysis indicated that bcl-2 and c-
fos
but not p53 and c-
myc
may participate in mediating H
2
O
2
-Fe(II)–induced VSMC apoptosis.

Conclusions
Different reactive oxygen species exert distinct effects on VSMCs, with O
2
−
inducing proliferation and H
2
O
2
causing apoptosis. Thus, reactive oxygen species might participate in atherosclerosis, restenosis, and hypertension in a dual manner by stimulating proliferation and triggering apoptosis of VSMCs.
Physiological Concentrations of Estradiol Attenuate Endothelin 1–Induced Coronary Vasoconstriction In Vivo
Authors: Sudhir Krishnankutty , Ko Eitetsu , Zellner Christian , Wong Hubert E. , Hutchison Stuart J. , Chou Tony M. , Chatterjee Kanu
Published: June 2012

Background
Estrogens are cardioprotective hormones and are reported to have antianginal properties. We examined the effect of physiological concentrations of 17β-estradiol on coronary reactivity in anesthetized female farm pigs.

Methods and Results
Epicardial coronary cross-sectional area (CSA) was assessed by two-dimensional intravascular ultrasound, average coronary peak flow velocity (APV) by intravascular Doppler velocimetry, and coronary blood flow (CBF) was calculated. Dose-response curves to intracoronary endothelin-1 (ET-1, 1 pmol/L to 10 nmol/L), the selective ET
B
receptor agonist sarafotoxin (1 pmol/L to 10 nmol/L), and serotonin (0.1 nmol/L to 1 μmol/L) were assessed before and after a 10-minute infusion of intracoronary estradiol (1 nmol/L). Before estradiol administration, ET-1 induced significant dose-dependent decreases in CSA, APV, and CBF. Estradiol attenuated ET-1–induced epicardial vasoconstriction (
P
<.001) as well as ET-1–induced decreases in APV (
P
=.05) and CBF (
P
=.012). In an additional five pigs, vehicle (DMSO) had no effect on ET-1–induced coronary vasoconstriction. Before estradiol administration, sarafotoxin induced no net change in CSA but induced increases in APV and CBF, the extent of which did not change significantly after estradiol. Serotonin induced small decreases in CSA but increased APV and CBF. Estradiol did not influence serotonin-induced changes in CSA, APV, or CBF.

Conclusions
We conclude that estradiol attenuates ET-1–induced vasoconstriction, possibly through effects on the ET
A
receptor, because selective ET
B
receptor-induced stimulation with sarafotoxin remained unchanged. Such an effect on the ET
A
receptor may relate to the antianginal properties of estrogens.
Bimodal Distribution of Angiographic Measures of Restenosis Six Months After Coronary Stent Placement
Authors: Schömig Albert , Kastrati Adnan , Elezi Shpend , Schühlen Helmut , Dirschinger Josef , Dannegger Felix , Wilhelm Manfred , Ulm Kurt
Published: June 2012

Background
Restenosis has been perceived as the tail end of a normal distribution of the response of the vessel to the intervention. However, recent studies have described a bimodal distribution for de novo lesions after percutaneous transluminal coronary angioplasty. This finding suggests that some lesions may be more susceptible for restenosis. Whether this holds true for a wider spectrum of lesions undergoing stent placement is not yet known. The present study analyzes the frequency distribution of angiographic indexes of restenosis 6 months after coronary stent implantation.

Methods and Results
Quantitative angiographic evaluation was performed in 1084 lesions of 1084 patients before, immediately after, and 6 months after successful Palmaz-Schatz stent placement; this represented 80.4% of patients eligible for follow-up angiography. Principal end points of the analysis were angiographic indexes of restenosis at 6 months. Twenty-two lesions that became totally occluded at follow-up were excluded from most parts of the analysis. Diameter stenosis, minimal luminal diameter (MLD), and lumen loss at 6 months did not follow a normal pattern; the bimodal pattern was demonstrated through deconvolution that yielded two separate normal components delineating two lesion populations, which developed distinctively different degrees of lumen renarrowing. The first and larger subgroup of lesions, which was less prone to restenosis, was centered around a mean value of 27% for diameter stenosis and 2.19 mm for MLD, whereas the second subgroup, with a greater tendency for restenosis, was situated around a mean value of 68% for diameter stenosis and 0.76 mm for MLD. The intersection point between the two theoretical normal distribution components was 53.5% for diameter stenosis and 1.09 mm for MLD at follow-up.

Conclusions
Frequency-distribution curves of angiographic indexes of restenosis after coronary stent placement have a bimodal pattern, suggesting the existence of two distinct populations with different propensity to restenosis. These findings may encourage future efforts for the timely identification of the subset with a higher risk as the target of specific antirestenotic strategies.
Cardiopulmonary Interactions After Fontan Operations
Authors: Shekerdemian Lara S. , Bush Andrew , Shore Darryl F. , Lincoln Christopher , Redington Andrew N.
Published: June 2012

Background
The low-output state is the chief cause of morbidity and mortality after Fontan operations. An alternative hemodynamic tool would be a welcome addition for these patients, who are typically resistant to conventional therapeutic measures.

Methods and Results
The hemodynamic effects of conversion from conventional intermittent positive pressure ventilation (IPPV) to cuirass negative pressure ventilation (NPV) was investigated in nine acute postoperative Fontan patients on the pediatric intensive care unit and nine anesthetized patients undergoing cardiac catheterization in the convalescent phase after Fontan operations. Pulmonary blood flow was measured using the direct Fick method during IPPV and after a brief period of NPV. In one subgroup of patients, pulmonary blood flow was measured again after reinstitution of IPPV, and in a second subgroup, pulmonary blood flow was measured after an extended period of NPV. A brief period of NPV increased pulmonary blood flow from 2.4 to 3.5 L · min
−1
· /m
−2
, with a mean increase of 42%. Pulmonary blood flow continued to improve, with a total increase of 54% after an extended period of NPV. Values fell toward baseline after reinstitution of IPPV. Heart rate was unchanged during NPV, and the improvement in pulmonary blood flow was achieved by an increase in stroke volume from 25 mL/m
2
to 37 mL/m.
2

Conclusions
Through improvement of the stroke volume alone, NPV brought about a marked increase in the pulmonary blood flow and, hence, cardiac output of Fontan patients. An improvement in cardiac output of this order, and by this mechanism, is currently unmatched by any therapeutic alternatives.
Insulin as a Vascular and Sympathoexcitatory Hormone
Authors: Scherrer Urs , Sartori Claudio
Published: June 2012

Abstract
The past several years have witnessed a major surge of interest in the cardiovascular actions of insulin. This interest has stemmed on the one hand from epidemiological studies that demonstrated an association between obesity, insulin resistance, and hypertension, leading to the so-called insulin hypothesis of hypertension. On the other hand, this interest has been stimulated by experimental evidence suggesting that the vascular actions of insulin may play a role in its main action, namely the promotion of glucose uptake in skeletal muscle tissue. Two tenets have emerged about how insulin may exert its cardiovascular actions. First, it is now firmly established that acute insulin administration stimulates sympathetic nerve activity in both animals and humans. Second, there is increasing evidence that insulin stimulates muscle blood flow, an effect that appears to be mediated at least in part by an endothelium-dependent mechanism. This review summarizes the current understanding and gaps in knowledge on cardiovascular actions of insulin in humans and pathophysiological consequences of derangements of such actions.