bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Therapeutic Improvements and 28-Day Case Fatality in Patients Hospitalized With Acute Myocardial Infarction Between 1978 and 1993 in the REGICOR Study, Gerona, Spain
Authors: Gil M. , Marrugat J. , Sala J. , Masiá R. , Elosua R. , Albert X. , Pena A. , Vila J. , Pavesi M. , Pérez G.
Published: June 2012

Background
—The aim of this study was to analyze 28-day case fatality trends between 1978 and 1993 among hospitalized acute myocardial infarction (AMI) patients in the REGICOR registry, Gerona, Spain, and relate them to thrombolytic and antiplatelet drug use and changes in patient characteristics.

Methods and Results
—A total of 2053 consecutive patients 25 to 74 years of age with a first Q-wave AMI admitted to the reference hospital between 1978 and 1993 were registered. Clinical characteristics and patient management were recorded. Four 4-year periods were considered: 1978 to 1981, 1982 to 1985 (prethrombolytic therapy), 1986 to 1989 (thrombolytic and antiplatelet drugs introduced), and 1990 to 1993 (thrombolytic and antiplatelet drugs used routinely). The end point was death at 28 days. Case fatality at 28 days decreased 6% per year between 1978 and 1993. A logistic model adjusted for comorbidity and severity showed the last 3 periods to present a steep decrease in the OR of death at 28 days: 0.86 (95% CI, 0.52 to 1.41), 0.59 (95% CI, 0.35 to 0.99), and 0.40 (95% CI, 0.24 to 0.69), respectively, compared with the first period. After 1986, 85.7% of the 112 lives saved could be attributed to the use of antiplatelet and thrombolytic drugs. Adjusted relative risk reduction was 56.0% for antiplatelet drugs, 34.1% for thrombolytic drugs, and 77.9% for the 2 combined.

Conclusions
—Our results strongly suggest that new therapies introduced since 1986 have contributed to the decrease in 28-day case fatality of patients admitted with a first Q-wave AMI. This decrease could be attributable mainly to the use of antiplatelet and thrombolytic drugs. These findings should encourage the routine use of thrombolytic and antiplatelet drugs and particularly their combination in the acute phase of AMI.
Adenovirus-Mediated Delivery of Fas Ligand Inhibits Intimal Hyperplasia After Balloon Injury in Immunologically Primed Animals
Authors: Luo Zhengyu , Sata Masataka , Nguyen Thao , Kaplan Johanne M. , Akita Geoffrey Y. , Walsh Kenneth
Published: June 2012

Background
—Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explored the efficacy of adenovirus-mediated transfer of
Fas ligand
, a cytotoxic gene with immunomodulatory properties, in inhibiting injury-induced vascular lesion formation in both naive and immunologically primed animals.

Methods and Results
—Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or β-galactosidase (Ad-βgal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-βgal–treated vessels (
P
<0.05), whereas the cytostatic agent Ad-p21 decreased lesion size by 58% (
P
<0.05). In animals preimmunized with an adenoviral vector containing no transgene, Ad-FasL significantly inhibited neointima formation (73% reduction,
P
<0.05), but Ad-p21 failed to inhibit neointima formation relative to controls. Immunologically primed rats displayed robust T-cell infiltration in Ad-p21– and Ad-βgal–treated vessels, but T-cell infiltration was markedly attenuated in Ad-FasL–treated vessels.

Conclusions
—Our data demonstrate that adenovirus-mediated Fas ligand delivery can inhibit intimal hyperplasia in both immunologically primed and naive animals, whereas the efficacy of an adenovirus-mediated p21 delivery is limited to immunologically naive animals. This study documents, for the first time, the therapeutic efficacy of intravascular adenoviral gene transfer in animals with preexisting immunity to adenovirus.
ApoCIII Gene Variants Modulate Postprandial Response to Both Glucose and Fat Tolerance Tests
Authors: Waterworth Dawn M. , Ribalta Josep , Nicaud Viviane , Dallongeville Jean , Humphries Steve E. , Talmud Philippa
Published: June 2012

Background
—We investigated the relationship between variation in the apolipoprotein (apo) AI-CIII-AIV gene cluster and response to an oral glucose test (OGTT) and oral fat load test (OFTT) in the EARSII group of young, healthy male offspring whose fathers had had a myocardial infarction before the age of 55 years (cases, n=407) compared with age-matched controls (n=415). The apoCIII variations examined were C3238G (
Sst
I) in the 3′-UTR, C1100T in exon 3, C-482T in the insulin response element (IRE), and T-2854G in the apoCIII-AIV intergenic region.

Methods and Results
—The postprandial response was regulated by variation at the T-2854G and C3238G sites. After the OFTT, carriers of the rare alleles had delayed clearance of triglyceride (Tg) levels; G-2854 carriers showed the largest effect on Tg (AUC, 24% greater,
P
<0.002; peak, 19% greater,
P
<0.005), and G3238 carriers showed a smaller response (AUC, 13% greater,
P
<0.05; peak, 13% greater,
P
=0.03). However, after adjustment for fasting level of Tg, only the effect with the T-2854G remained significant. Variation at the C-482T (IRE) determined response to the OGTT, with carriers of the rare T-482 having significantly elevated glucose (28.7% AUC,
P
=0.013) and insulin (20.5% AUC,
P
<0.01) concentrations.

Conclusions
—These data suggest that specific genetic variants at the apoCIII gene locus differentially affect postprandial and response to OGTT and suggest a novel mechanism for the effects of variation at this locus on risk for atherosclerosis.
Atrioventricular Nodal Conduction During Atrial Fibrillation
Authors: Garrigue Stéphane , Mowrey Kent A. , Fahy Gerard , Tchou Patrick J. , Mazgalev Todor N.
Published: June 2012

Background
—Posteroseptal ablation of the atrioventricular node (AVN) has been proposed as a means to slow the ventricular rate during atrial fibrillation (AF). The suggested mechanism is elimination of the AVN “slow pathway.” On the basis of the unpredictable success of the procedure, we hypothesize that, in fact, the slow pathway is preserved. Therefore, the slowing of the ventricular rate results from reduced bombardment of the AVN.

Methods and Results
—In 8 rabbit heart atrial-AVN preparations, cooling of the posterior and/or the anterior AVN approaches revealed nonspecific effects on the slow and fast pathway portions of the AVN conduction curve. In 13 other preparations, simulated AF during posterior cooling (n=6) prolonged the His-His (H-H) intervals but did not reveal specific slow pathway injury. In the remaining 7 preparations, AF was applied before and after posteroseptal surgical cuts. During AF with posterior origin, the cuts resulted in longer mean H-H along with slowing of the AVN bombardment rate. However, there was no change in the minimum observed H-H, suggesting an intact slow pathway. During AF with anterior origin, the mean and the shortest H-H remained unchanged before and after the cuts in all preparations. This was associated with the maintenance of high-rate AVN bombardment.

Conclusions
—Posteroseptal ablation does not eliminate the slow pathway. Ventricular rate slowing can be obtained if the ablation procedure results in a posteroanterior intra-atrial block leading to a reduction of the rate of AV nodal bombardment.
Two-Year Follow-Up After Catheter-Based Radiotherapy to Inhibit Coronary Restenosis
Authors: Teirstein Paul S. , Massullo Vincent , Jani Shirish , Russo Robert J. , Cloutier David A. , Schatz Richard A. , Guarneri Erminia M. , Steuterman Stephen , Sirkin Kathleen , Norman Shela , Tripuraneni Prabhakar
Published: June 2012

Background
—Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis.

Methods and Results
—A double-blind, randomized trial was undertaken to compare
192
Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0.03-in) ribbon containing sealed sources of either
192
Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to
192
Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the
192
Ir group (15.4% versus 44.8%;
P
<0.01). Nontarget-lesion revascularization was similar in
192
Ir and placebo patients (19.2% versus 20.7%;
P
=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in
192
Ir-treated versus placebo-treated patients (23.1% versus 51.7%;
P
=0.03). No patient in the
192
Ir group sustained a target-lesion revascularization later than 10 months.

Conclusions
—At 2-year clinical follow-up, treatment with
192
Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the
192
Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.
Endothelin-1 and Blood Pressure After Inhibition of Nitric Oxide Synthesis in Human Septic Shock
Authors: Avontuur Jurgen A. M. , Boomsma Frans , van den Meiracker Anton H. , de Jong Frank H. , Bruining Hajo A.
Published: June 2012

Background
—The systemic hypotension during human sepsis has been ascribed to increased production of nitric oxide (NO). Therefore, inhibitors of NO synthesis have been used in the treatment of hypotension in patients with septic shock. In addition, NO production may inhibit the synthesis and vasoconstrictor effects of endothelin-1 (ET-1). In this study, we tested whether ET-1 contributed to the vasopressor action of the NO synthase inhibitor
N
G
-nitro-
l
-arginine methyl ester (L-NAME) in patients with severe septic shock.

Methods and Results
—Compared with healthy volunteers, patients with septic shock had increased plasma levels of nitrite/nitrate (37±5 [SEM] versus 12±5 mmol/L,
P
<0.01), the stable end products of NO metabolism, and ET-1 (45±7 versus 3±2 pg/mL,
P
<0.001). Plasma ET-1 concentration was not related to plasma nitrite/nitrate concentration or blood pressure. Continuous infusion of L-NAME (1 mg · kg
−1
· h
−1
IV) for 12 hours increased mean arterial pressure by 43±5% and systemic vascular resistance by 64±10% (both
P
<0.01). The increase in blood pressure and systemic vascular resistance correlated positively with the level of ET-1 (both
P
<0.005) but not with plasma nitrite/nitrate level. L-NAME infusion did not result in significant changes in the plasma concentrations of ET-1 or nitrite/nitrate.

Conclusions
—NO and ET-1 may both play a role in the cardiovascular derangements of human sepsis. Although L-NAME does not increase ET-1 concentration in patients with septic shock, the vasopressor response induced by L-NAME depends on the plasma level of ET-1. These findings may indicate that inhibitors of NO synthesis unmask a tonic pressor response of ET-1 in human septic shock.
Coronary Calcium Does Not Accurately Predict Near-Term Future Coronary Events in High-Risk Adults
Authors: Detrano Robert C. , Wong Nathan D. , Doherty Terence M. , Shavelle Robert M. , Tang Weiyi , Ginzton Leonard E. , Budoff Matthew J. , Narahara Kenneth A.
Published: June 2012

Background
—Prognostic risk models have had limited success in predicting coronary events in subjects with multiple risk factors. We and others have proposed an alternative approach using radiographically detectable coronary calcium. We evaluated and compared the predictive value of these 2 approaches for determining coronary event risk in asymptomatic adults with multiple coronary risk factors. In addition, we assessed the predictive value of a risk model that included calcium score and cardiac risk-factor data.

Methods and Results
—We recruited 1196 asymptomatic high-coronary-risk subjects who then underwent risk-factor assessment and cardiac electron-beam CT (EBCT) scanning and were followed up for 41 months with a 99% success rate. We applied the Framingham model and our data-derived risk model to determine the 3-year likelihood of a coronary event. The mean age of our cohort was 66 years, and mean 3-year Framingham risk was 3.3±3.6%. Sixty-eight percent (818 subjects) had detectable coronary calcium. There were 17 coronary deaths (1.4%) and 29 nonfatal infarctions (2.4%). The receiver operating characteristic (ROC) curve areas calculated from the Framingham model, our data-derived risk model, and the calcium score were 0.69±0.05, 0.68±0.05, and 0.64±0.05, respectively (
P
=NS). When calcium score was included as a variable in the data-derived model, the ROC area did not change significantly (0.68±0.05 to 0.71±0.04;
P
=NS).

Conclusions
—Neither risk-factor assessment nor EBCT calcium is an accurate event predictor in high-risk asymptomatic adults. EBCT calcium score does not add significant incremental information to risk factors, and its use in clinical screening is not justified at this time.
Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure
Authors: Baruch Lawrence , Anand Inder , Cohen Ira S. , Ziesche Susan , Judd Dianne , Cohn Jay N.
Published: June 2012

Background
—ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heart failure. An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects.

Methods and Results
—Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were randomly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their usual ACE inhibitor therapy. Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy. A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition. Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater reduction in pulmonary capillary wedge pressure at 3, 4, and 8 hours and during the prespecified 4- to 8-hour interval after the dose and in systolic blood pressure at 2, 3, 6, 8, and 12 hours and 4 to 8 hours after the dose. A pressure reduction from valsartan 80 mg did not achieve statistical significance. After 4 weeks of therapy, net reductions in 0-hour trough pulmonary capillary wedge pressure (−4.3 mm Hg;
P
=0.16), pulmonary artery diastolic pressure (−4.7 mm Hg;
P
=0.013), and systolic blood pressure (−6.8 mm Hg;
P
=0.013) were observed in the valsartan 160 mg group compared with placebo. After 4 weeks of therapy, plasma aldosterone was reduced by valsartan 80 mg BID (−52.1 pg/mL;
P
=0.001) and 160 mg BID (−47.8 pg/mL;
P
<0.001) compared with placebo, and there was a trend for a reduction in plasma norepinephrine (−97 pg/mL;
P
=0.10). Seventy-four of the 83 patients completed the trial.

Conclusions
—Physiologically active levels of angiotensin II persist during standard long-term ACE inhibitor therapy.
Central Pulse Pressure Is a Major Determinant of Ascending Aorta Dilation in Marfan Syndrome
Authors: Jondeau Guillaume , Boutouyrie Pierre , Lacolley Patrick , Laloux Brigitte , Dubourg Olivier , Bourdarias Jean-Pierre , Laurent Stéphane
Published: June 2012

Background
—In patients with Marfan syndrome (MFS), brachial pulse pressure (PP) has been recognized as a risk factor for aortic dilatation, leading to aortic dissection, the main cause of premature death. However, the relationships between aortic PP, aortic stiffness, and aortic root dilation have not been investigated. Our main objective was to determine whether central PP, which takes into account wave reflections and aortic stiffness, is a better determinant of ascending aorta diameter than brachial PP in MFS patients.

Methods and Results
—Twenty patients with confirmed MFS and 20 age- and sex-matched control subjects were included in this cross-sectional, noninvasive study. Elastic properties of the abdominal aorta and common carotid, common femoral, and radial arteries were calculated from the pulsatile changes in arterial diameter and pressure. The ascending aorta diameter, measured with conventional echocardiography, was 37% larger in MFS than in control subjects (
P
<0.001). Arterial distensibility was 38% lower in MFS than in control subjects at the site of the abdominal aorta (
P
<0.01) but not at other sites (common carotid, common femoral, and radial arteries). Independently of age and body surface area, ascending aorta diameter was positively correlated with carotid PP in MFS (
P
<0.01) and negatively in control subjects (
P
<0.01) but was not correlated with brachial PP and mean blood pressure.

Conclusions
—In patients with MFS, local PP, estimated from carotid PP, was a major determinant of ascending aorta diameter, whereas brachial PP was not. Increased arterial stiffness was confined to the aorta.
Copulsation Balloon for Right Ventricular Assistance
Authors: Trumble Dennis R. , Park Chong S. , Magovern James A.
Published: June 2012

Background
—Options for management of acute right ventricular (RV) failure are limited. This report describes preliminary testing of a temporary RV assist device that acts by direct compression of the RV. The system comprises a pancake-shaped silicone balloon (5 cm diameter) connected to a drive console that delivers a 65-mL pneumatic pulse during cardiac systole.

Methods and Results
—Initial in vivo tests were performed on 6 pigs (weight, 41±4 kg). RV wall motion and stroke volume were monitored via transesophageal echocardiography. Acute RV failure was created by graded right coronary ligation, which yielded a 63% reduction in RV stroke volume (39.9±8.2 to 14.7±1.9 mL;
P
<0.002). We secured the balloon over the RV free wall by attaching it to the edges of the opened pericardium. The sternum was then reapproximated, and data were collected with the device off and on (every beat). Device placement had no deleterious effect on RV function. Balloon activation returned RV stroke volumes to normal (37.8±9.2 mL) and increased mean pulmonary artery pressures from 13±2 to 16±3 mm Hg (
P
<0.01). RV compression did not induce or exacerbate tricuspid regurgitation. Mean aortic pressure improved from postinfarction levels but did not return to normal.

Conclusions
—We conclude that the pulmonary circulation can be supported in the short term via cardiac compression and that balloon copulsation techniques for short-term RV failure should be tested in long-term models.
High-Dose Heparin Impairs Nitric Oxide Pathway and Vasomotion in Rats
Authors: Bachetti Tiziana , Pasini Evasio , Clini Enrico , Cremona George , Ferrari Roberto
Published: June 2012

Background
—Platelet-activating effects have been reported with high-dose heparin in acute thrombotic disorders. Recent studies have shown that increased platelet aggregation is due to reduced nitric oxide (NO) production in endothelial cells cultured in the presence of high-dose heparin. The aim of this study was to determine whether heparin can affect the NO pathway and the regulation of the vascular tone in vivo.

Methods and Results
—Anesthetized and mechanically ventilated Sprague-Dawley rats were treated with high-dose heparin. After 4 hours, the endothelial constitutive NO synthase (ecNOS) protein content in the aorta decreased (36% reduction,
P
<0.05), as detected by immunoblotting, and NO-dependent vascular reactivity was impaired. In fact, the increase in mean arterial blood pressure after inhibition of ecNOS with
N
G
-nitro-
l
-arginine methyl ester (30 mg/kg) was smaller in heparin-treated animals than in controls (+26.9±4.8 versus +48.3±9.1 mm Hg,
P
<0.05), and further infusion of the biological ecNOS substrate
l
-arginine (0.5 g/kg) was ineffective in reversing systemic vasoconstriction (−1% versus 28% vasodilatation,
P
<0.001).

Conclusions
—High-dose heparin can significantly affect vascular reactivity in vivo by downregulation of ecNOS protein expression.
Effects of Acute Angiotensin II Type 1 Receptor Antagonism and Angiotensin Converting Enzyme Inhibition on Plasma Fibrinolytic Parameters in Patients With Heart Failure
Authors: Goodfield Nicholas E. R. , Newby David E. , Ludlam Christopher A. , Flapan Andrew D.
Published: June 2012

Background
—Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT
1
) receptor antagonism have similar effects in patients with heart failure.

Methods and Results
—Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%;
P
=0.003) and PAI-1 (38%;
P
<0.001) antigen concentrations, which was associated with increases in t-PA (29%;
P
=0.03) and decreases in PAI-1 (48%;
P
=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (
P
<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (
P
<0.05).

Conclusions
—Acute AT
1
antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT
1
antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.
G894T Polymorphism in the Endothelial Nitric Oxide Synthase Gene Is Associated With an Enhanced Vascular Responsiveness to Phenylephrine
Authors: Philip Ivan , Plantefeve Gaetan , Vuillaumier-Barrot Sandrine , Vicaut Eric , LeMarie Claude , Henrion Daniel , Poirier Odette , Levy Bernard I. , Desmonts Jean Marie , Durand Geneviève , Benessiano Joelle
Published: June 2012

Background
—Differences in vascular reactivity to phenylephrine (PE) responsiveness have been largely evidenced in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Because nitric oxide (NO) strongly affects modulation of the vascular tone in response to vasopressor agents, we hypothesized that the G894T polymorphism of the endothelial NO synthase gene (
eNOS
) could be related to changes in the pressor response to PE.

Methods and Results
—The protocol was performed in 68 patients undergoing coronary artery bypass grafting (n=33) or valve surgery (n=35) in whom mean arterial pressure decreased below 65 mm Hg during normothermic CPB. Under constant and nonpulsatile pump flow conditions (2 to 2.4 L · min
−1
· m
−2
), a PE dose-response curve was generated by the cumulative injection of individual doses of PE (25 to 500 μg). The G894T polymorphism of the
eNOS
gene was determined, and 3 groups were defined according to genotype (TT, GT, and GG). Groups were similar with regard to perioperative characteristics. The PE dose-dependent response was significantly higher in the allele 894T carriers (TT and GT) than in the homozygote GG group (
P
=0.02), independently of possible confounding variables.

Conclusions
—These results evidenced an enhanced responsiveness to α-adrenergic stimulation in patients with the 894T allele in the
eNOS
gene.
Prevention of Distal Embolization During Saphenous Vein Graft Lesion Angioplasty
Authors: Carlino Mauro , De Gregorio Joseph , Di Mario Carlo , Anzuini Angelo , Airoldi Flavio , Albiero Remo , Briguori Carlo , Dharmadhikari Aniruddha , Sheiban Imad , Colombo Antonio
Published: June 2012

Background
—Repeat coronary artery bypass graft surgery (CABG) is associated with a high morbidity and mortality, rendering percutaneous treatment of saphenous vein graft (SVG) lesions an attractive alternative. However, percutaneous interventions of degenerated SVGs carries high risk of distal embolization.

Methods and Results
—This study reports our initial experience with the PercuSurge GuardWire, a new device developed to prevent embolization during treatment of degenerated SVG. This device consists of a 190-cm-long, hollow 0.014-in guidewire with a central lumen connected to a distal occlusion balloon. A dedicated inflation device (the MicroSeal Adapter) was used to inflate the distal balloon and maintain complete lumen occlusion during balloon dilatation and stent implantation. A monorail aspiration catheter, connected to a vacuum syringe, was used to evacuate atherosclerotic and thrombotic debris. Angioplasty with stent implantation was performed in 15 degenerated SVGs (18 lesions). Procedural success was achieved in all patients with normal postprocedure flow (Thrombolysis in Myocardial Infarction grade 3). No distal embolization was observed. There were no major in-hospital adverse clinical events, including Q-wave or non–Q-wave myocardial infarction, emergency CABG, or death. All patients were asymptomatic at discharge.

Conclusions
—This preliminary series supports the feasible use of the PercuSurge GuardWire for retrieval of plaque debris and prevention of embolization in degenerated SVGs. The good tolerance of temporary occlusions without angiographic or clinical evidence of distal embolization represents encouraging early findings.
Additive Effects of Late Preconditioning Produced By Monophosphoryl Lipid A and the Early Preconditioning Mediated By Adenosine Receptors and K
ATP
Channel
Authors: Stambaugh Kristyne , Elliott Gary T. , Jacobson Kenneth A. , Liang Bruce T.
Published: June 2012

Background
—The cardioprotective effect of preconditioning can be exerted within 1 to 2 hours after initial ischemia, termed classical or early preconditioning, or can reappear 24 hours later as second window or late preconditioning. The objective of this study was to study the interaction between late and early preconditioning and to determine the potential underlying mechanism.

Methods and Results
—Adenosine receptor agonists and a K
ATP
channel opener were used to achieve early preconditioning, and Monophosphoryl lipid A (MLA) was used to induce late preconditioning. Cultured chick ventricular myocytes were used as a myocyte model of simulated ischemia and preconditioning. Prior treatment of the myocyte with MLA caused a dose-dependent decrease in the ischemia-induced myocyte injury 24 hours later, consistent with a late preconditioning effect. L-NMMA, glibenclamide, or 5-hydroxydecanoic acid administered during the ischemia blocked the MLA effect. Twenty four hours after MLA treatment, a 5-minute exposure to ischemia, adenosine, adenosine A
1
agonist CCPA, or A
3
agonist resulted in less myocyte injury during the subsequent prolonged ischemia, as compared with cells pretreated with the vehicle and subsequently exposed to the same early preconditioning stimuli. In addition to its ability to enhance the early preconditioning effect by A
1
and A
3
agonists, MLA pretreatment also increased the phorbol ester- and pinacidil-mediated early preconditioning effect.

Conclusions
—This study defined a novel interaction in which the cardioprotective effect of early preconditioning is additive to that of late preconditioning and raised the possibility that both agents can be used as combined therapy in the treatment of ischemic heart disease.
Radiofrequency Catheter Ablation of Common Atrial Flutter
Authors: Anselme F. , Saoudi N. , Poty H. , Douillet R. , Cribier A.
Published: June 2012

Background
—Creation of a complete bidirectional inferior vena cava–tricuspid annulus isthmus block (CBIB) by radiofrequency catheter ablation is now a well-accepted criterion for prevention of common atrial flutter (AFl) recurrences. However, some patients still complain of palpitations after ablation, and it is not known whether these are related to AFl recurrences or to other arrhythmias.

Methods and Results
—Among 100 consecutive patients referred to our institution for AFl ablation, CBIB was created in 83. There were 54 patients (group A) in whom AFl was the only documented arrhythmia before ablation and 29 patients (group B) in whom atrial fibrillation (AFib) had been documented in addition to AFl. An electrophysiological control study was performed in 40 patients 1 to 3 months after ablation. Arrhythmic events, medications, and functional status were evaluated at midterm follow-up (n=77; 14.7±8.4 months; range, 4 to 34 months). The SF-36 questionnaire and the Symptom Checklist—Frequency and Severity Scale specific for cardiac arrhythmia were used to assess quality of life in 63 patients at long-term follow-up (27.1±8.5 months). Recurrence of AFl was documented in only 1 patient 6 months after ablation. AFib was recorded in 28 patients (36.4%), and atypical AFl was found in 3 patients. Thirty-two group A patients (66.7%) and 17 group B patients (58.6%) were still arrhythmia free at midterm follow-up. Even at long-term follow-up and in group B patients, AFl ablation was followed by a clear improvement in quality of life.

Conclusions
—Palpitations after creation of CBIB are due mostly to AFib but not to AFl recurrence. This technique provides a significant and persistent clinical benefit and may suppress all atrial arrhythmia in a subset of patients suffering from both AFl and AFib.
First Redo Heart Valve Replacement
Authors: Weerasinghe Arjuna , Edwards Maria-Benedicta , Taylor Kenneth M.
Published: June 2012

Background
—The United Kingdom Heart Valve Registry (UKHVR) has recently completed collecting information on 52 659 heart valve replacements (in 47 718 patients) performed during the period 1986 to 1995 in the whole of the United Kingdom. Information stored in the UKHVR’s computer database was used for this study. Factors affecting the time from first prosthesis to first redo prosthesis were analyzed and provided useful predictive information. The association between prosthesis-induced local pathological processes and redo valve size was investigated.

Methods and Results
—This is a retrospective study of 43 301 patients (from among 47 718 in the database) undergoing single-site replacement of a diseased native mitral or aortic valve over a 10-year period from January 1986 to December 1995 in the United Kingdom. Of these patients, 1051 (2.43%) went on to have a first redo heart valve replacement. Valve survival analysis (Cox regression and Kaplan-Meier curves) was used to study the natural progression to the first redo heart valve replacement. Female sex and having a replacement at the aortic rather than the mitral position were both associated with a longer interval to the first redo operation. Regression analysis showed the size of the redo valve to be influenced by the interoperative time. This effect was more pronounced at the mitral position.

Conclusions
—Females and patients having an aortic valve replacement exhibit a longer interval to the first redo operation than do males and patients having mitral valve replacements, respectively. The time from the first replacement to the first redo operation significantly affects the size of the first redo valve.
Automated Heparin-Delivery System to Control Activated Partial Thromboplastin Time
Authors: Cannon Christopher P. , Dingemanse Jasper , Kleinbloesem Cornelis H. , Jannett Thomas , Curry Kenneth M. , Valcke Christian P.
Published: June 2012

Background
—Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials.

Methods and Results
—We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer-based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within ±10 seconds of the target (prespecified primary end point), and 89% were within a ±15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range ±15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples.

Conclusions
—These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice.
Percutaneous Mechanical Mitral Commissurotomy With a Newly Designed Metallic Valvulotome
Authors: Cribier Alain , Eltchaninoff Hélène , Koning René , Rath Pratap C. , Arora Ramesh , Imam Adel , El-Sayed Mustapha , Dani Sameer , Derumeaux Geneviève , Benichou Jacques , Tron Christophe , Janorkar Satej , Pontier Gérard , Letac Brice
Published: June 2012

Background
—Percutaneous balloon valvotomy has become a common treatment of mitral stenosis, but the cost of the procedure remains a limitation in countries with restricted financial resources, leading to a frequent reuse of the disposable catheters. To overcome this limitation, a reusable metallic valvotomy device has been developed with the goals of both improving the mitral valvotomy results and decreasing the cost of the procedure.

Methods and Results
—The device consists of a detachable metallic cylinder with 2 articulated bars screwed onto the distal end of a disposable catheter whose proximal end is connected to an activating pliers. By the transseptal route, the device is advanced across the valve over a traction guidewire. Squeezing the pliers opens the bars up to a maximum extent of 40 mm. The clinical experience consisted of 153 patients with a broad spectrum of mitral valve deformities. The procedure was successful in 92% of cases and resulted in a significant increase in mitral valve area, from 0.95±0.2 to 2.16±0.4 cm
2
. No increase in mitral regurgitation was noted in 80% of cases. Bilateral splitting of the commissures was observed in 87%. Complications were 2 cases of severe mitral regurgitation (1 requiring surgery), 1 pericardial tamponade, and 1 transient cerebrovascular embolic event. In this series, the maximum number of consecutive patients treated with the same device was 35.

Conclusions
—The results obtained with this new device are encouraging and at least comparable to those of current balloon techniques. Multiple uses after sterilization should markedly decrease the procedural cost, a major advantage in countries with limited resources and high incidence of mitral stenosis.
Development of the Cardiac Conduction Tissue in Human Embryos Using HNK-1 Antigen Expression
Authors: Blom Nico A. , Gittenberger-de Groot Adriana C. , DeRuiter Marco C. , Poelmann Rob E. , Mentink Monica M. T. , Ottenkamp Jaap
Published: June 2012

Background
—Abnormal atrial automaticity in young patients with structurally normal hearts is often located around the pulmonary veins and in sinus venosus–related parts of the right atrium. We hypothesize that these ectopic pacemaker sites correspond to areas of embryonic myocardium with an early phenotypic differentiation, as indicated by differences in antigen expression during normal cardiac development.

Methods and Results
—In human embryos ranging in age from 42 to 54 days of gestation, the development of the cardiac conduction system was studied with the use of HNK-1 immunohistochemistry. HNK-1 stains the developing atrioventricular conduction system, ie, the bundle branches, His bundle, right atrioventricular ring, and retroaortic ring. In addition, the myocardium around the common pulmonary vein showed transient HNK-1 antigen expression. In the right atrium, 3 HNK-1–positive connections were demonstrated between the sinoatrial node and the right atrioventricular ring. An anterior tract through the septum spurium connects the sinoatrial node with the anterior right atrioventricular ring, and 2 posterior tracts connect the sinoatrial node with the posterior right atrioventricular ring through the right venous valve (future crista terminalis) and sinus septum, encircling the coronary sinus. The medioposterior part of the right atrioventricular ring connected to the His bundle and the medioanterior part form 2 node-like structures.

Conclusions
—In patients with abnormal atrial automaticity, the distribution of left and right atrial pacemaker foci correspond to areas of the embryonic myocardium that temporarily express the HNK-1 antigen.
Adenoviral Gene Transfer of the Human V2 Vasopressin Receptor Improves Contractile Force of Rat Cardiomyocytes
Authors: Laugwitz Karl-Ludwig , Ungerer Martin , Schöneberg Torsten , Weig Hans-Jörg , Kronsbein Kai , Moretti Alessandra , Hoffmann Katrin , Seyfarth Melchior , Schultz Günter , Schömig Albert
Published: June 2012

Background
—In congestive heart failure, high systemic levels of the hormone arginine vasopressin (AVP) result in vasoconstriction and reduced cardiac contractility. These effects are mediated by the V1 vasopressin receptor (V1R) coupled to phospholipase C β-isoforms. The V2 vasopressin receptor (V2R), which promotes activation of the Gs/adenylyl cyclase system, is physiologically expressed in the kidney but not in the myocardium. Expression of a recombinant V2R (rV2R) in the myocardium could result in a positive inotropic effect via the endogenous high concentrations of AVP in heart failure.

Methods and Results
—A recombinant adenovirus encoding the human V2R (Ad-V2R) was tested for its ability to modulate the cardiac Gs/adenylyl cyclase system and to potentiate contractile force in rat ventricular cardiomyocytes and in H9c2 cardiomyoblasts. Ad-V2R infection resulted in a virus concentration-dependent expression of the transgene and led to a marked increase in cAMP formation in rV2R-expressing cardiomyocytes after exposure to AVP. Single-cell shortening measurements showed a significant agonist-induced contraction amplitude enhancement, which was blocked by the V2R antagonist, SR 121463A. Pretreatment of Ad-V2R-infected cardiomyocytes with AVP led to desensitization of the rV2R after short-term agonist exposure but did not lead to further loss of receptor function or density after long-term agonist incubation, thus demonstrating resistance of the rV2R to downregulation.

Conclusions
—Adenoviral gene transfer of the V2R in cardiomyocytes can modulate the endogenous adenylyl cyclase-signal transduction cascade and can potentiate contraction amplitude in cardiomyocytes. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in congestive heart failure by bypassing the desensitized β-adrenergic receptor signaling.
Myocardial Oxygenation During High Work States in Hearts With Postinfarction Remodeling
Authors: Murakami Yo , Zhang Yi , Cho Yong K. , Mansoor Abdul M. , Chung Jun K. , Chu Cuixia , Francis Gary , Ugurbil Kamil , Bache Robert J. , From Arthur H. L. , Jerosch-Herold Michael , Wilke Norbert , Zhang Jianyi
Published: June 2012

Background
—Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities.

Methods and Results
—Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with
31
P NMR and deoxymyoglobin (Mb-δ) with
1
H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 μg · kg
−1
· min
−1
IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-δ. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-δ.

Conclusions
—Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.
Relationships Among Electrophysiological Findings and Clinical Status, Heart Function, and Extent of DNA Mutation in Myotonic Dystrophy
Authors: Lazarus A. , Varin J. , Ounnoughene Z. , Radvanyi H. , Junien C. , Coste J. , Laforet P. , Eymard B. , Becane H. M. , Weber S. , Duboc D.
Published: June 2012

Background
—Impulse-conduction abnormalities and arrhythmias are common in myotonic dystrophy (MD). This study was performed to determine whether a correlation exists between electrophysiological (EP) testing data and clinical status, heart function, or size of the DNA abnormality (cytosine-thymine-guanine sequence repeat).

Methods and Results
—Eighty-three MD patients underwent invasive EP studies prompted primarily by the presence of asymptomatic conduction abnormalities. AV conduction disturbances were common and mainly distal (HV interval, 66.2±14 ms). AV conduction observed from the surface ECG was generally concordant with endocardial measurements. However, 11 of 20 patients with normal surface ECGs had abnormal subhisian conduction. Atrial arrhythmias were inducible in 41% of cases and correlated with prolongation of the AH interval (
P
=0.02) and a shorter atrial refractory period (
P
=0.04). Induction of ventricular arrhythmias (18%) correlated strongly with age (
P
=0.0003). After adjustment for age, the extent of DNA mutation correlated with the Walton score (
P
=0.0018) but not with conduction abnormalities or induction of arrhythmias.

Conclusions
—Prolongation of the HV interval is the most common conduction abnormality in MD and can be reliably recognized only by invasive EP testing. It raises the issue of prophylactic pacing to limit the incidence of sudden death in MD. Atrial and ventricular arrhythmias are often inducible, although their predictive value remains to be determined. Young age emerged as the most powerful predictor of inducible ventricular tachyarrhythmias. Conversely, we found no relationship between ECG or EP abnormalities recorded during invasive testing and the DNA mutation size or severity of peripheral muscle involvement.
Nonanticoagulant Heparin Prevents Coronary Endothelial Dysfunction After Brief Ischemia-Reperfusion Injury in the Dog
Authors: Kouretas Peter C. , Kim Young D. , Cahill Paul A. , Myers Adam K. , To Lam N. , Wang Yi-Ning , Sitzmann James V. , Hannan Robert L.
Published: June 2012

Background
—Coronary endothelial dysfunction after brief ischemia-reperfusion (IR) remains a clinical problem. We investigated the role of heparin and
N
-acetylheparin, a nonanticoagulant heparin derivative, in modulating coronary endothelial function after IR injury, with an emphasis on defining the role of the nitric oxide (NO)–cGMP pathway in the heparin-mediated effect.

Methods and Results
—Male mongrel dogs were surgically instrumented, and the effects of both bovine heparin and
N
-acetylheparin on coronary endothelial vasomotor function, expressed as percent change from baseline flow after acetylcholine challenge, were studied after 15 minutes of regional ischemia of the left anterior descending artery (LAD) followed by 120 minutes of reperfusion. In dogs treated with placebo (saline), coronary vasomotor function was significantly (
P
≤0.03) decreased after 15 and 30 minutes of reperfusion (65±12% and 73±12%) compared with preischemia (103±6%). In contrast, the vasodilatory response to the endothelium-independent vasodilator sodium nitroprusside was maintained during reperfusion. Preischemic administration of both bovine heparin and
N
-acetylheparin (6.0 mg/kg IV) preserved coronary endothelial function throughout reperfusion. In a parallel group of dogs, nitrate/nitrite (NOx) and cGMP levels in the LAD were measured after treatment and during 15-minute reperfusion. Preischemic administration of
N
-acetylheparin caused a significant increase in basal NOx and cGMP levels compared with saline controls. Pretreatment with
N
-acetylheparin also caused a significant increase in NOx and cGMP levels in the LAD after 15 minutes of reperfusion compared with IR alone.

Conclusions
—These results suggest that heparin preserves coronary endothelial function after brief IR injury by a mechanism independent of its anticoagulant activity and that the effect of heparin may be mediated in part by activation of the NO-cGMP pathway.
Inhibition of Nitric Oxide but Not Prostacyclin Prevents Poststenotic Dilatation in Rabbit Femoral Artery
Authors: Calvo William J. , Hajduczok George , Russell James A. , Diamond Scott L.
Published: June 2012

Background
—Poststenotic dilatation (PSD) occurs in a low-pressure region where recirculation eddies oscillate in size during the cardiac cycle. NO may be an important mediator of PSD.

Methods and Results
—Femoral arteries of 7 adult male New Zealand White rabbits were stenosed bilaterally to achieve a diameter reduction of 70.9±6.7% (n=14). At the time of stenosis, the adventitia of one of the arteries was coated with 1 mmol/L of
N
G
-nitro-
l
-arginine methyl ester (L-NAME) in 22% (wt/vol) Pluronic gel, while the contralateral vessel was coated with gel without L-NAME. In stenosed femoral arteries that were treated with gel without L-NAME, a maximum PSD of 30.99±7.92% (n=7) was observed in polymer casts at 3 days relative to the mean proximal diameter of 1.57±0.25 mm at a position 12 mm upstream of each stenosis. In contrast, the vessels treated with L-NAME exhibited a maximum PSD of only 7.16±8.81% (n=7) relative to the mean proximal diameter of 1.55±0.16 mm. L-NAME caused a 76.9% reduction (
P
<0.001, n=7) of PSD. Similarly,
N
G
-monomethyl-
l
-arginine 1 mmol/L and
N
G
-nitro-
l
-arginine 10 μmol/L attenuated PSD by 57.5% (
P
<0.001, n=6) and 63.9% (
P
<0.05, n=6), respectively. Indomethacin 10 μmol/L caused no reduction in PSD. Arterial rings obtained from the poststenotic region were more sensitive and responsive to acetylcholine than those obtained proximal to the stenosis.

Conclusions
—NO, but not prostacyclin, is a major mediator of PSD.