bluuebunny/crossref_metadata_2025 huggingface dataset:
Incremental Prognostic Value of Rest-Redistribution
201
Tl Single-Photon Emission Computed Tomography
Authors: Sharir Tali , Berman Daniel S. , Lewin Howard C. , Friedman John D. , Cohen Ishac , Miranda Romalisa , Agafitei Raluca D. , Germano Guido
Published: June 2012

Background
—The incremental prognostic value of rest-redistribution
201
Tl compared with stress and rest perfusion abnormalities has not been defined.

Methods and Results
—We identified 458 patients who underwent rest
201
Tl /stress (exercise or adenosine)
99m
Tc sestamibi single-photon emission computed tomography (SPECT) and had late (18 to 24 hours)
201
Tl imaging, were not revascularized within 60 days of SPECT, and were followed up at >1 year. SPECT images were visually analyzed with the use of a 20-segment model on a scale of 0 to 4. Thirty-seven cardiac deaths (CDs) and 17 nonfatal myocardial infarctions occurred. Univariate Cox proportional hazards analysis showed that the presence of a large amount of rest
201
Tl reversibility (rest-late summed difference score [SDS] of >8) was a significant predictor of CD (χ
2
=5.77,
P
=0.02) and CD or myocardial infarction (χ
2
=5.3,
P
=0.02). The CD rate was 9.3% y
−1
in patients with rest-late SDS of >8 compared with 3.6% y
−1
in patients with a mild/moderate amount of rest reversibility (rest-late SDS 3 to 8) and 3.4% y
−1
in patients with no rest reversibility (rest-late SDS <3) (
P
=0.029). Kaplan-Meier survival analysis demonstrated significantly lower cumulative survival rates in patients with rest-late SDS of >8 (
P
=0.01). Multivariate Cox proportional hazards analysis demonstrated that the presence of a large amount of resting reversibility was an independent and incremental predictor of CD after adjustment for stress and rest perfusion information. Multivariate logistic regression analysis demonstrated that resting reversibility was not an independent predictor of referral to coronary angiography and revascularization.

Conclusions
—The identification of a large amount of resting
201
Tl reversibility is an independent predictor of CD over stress and rest perfusion abnormalities.
Insulin Resistance Syndrome Predicts Coronary Heart Disease Events in Elderly Nondiabetic Men
Authors: Lempiäinen Päivi , Mykkänen Leena , Pyörälä Kalevi , Laakso Markku , Kuusisto Johanna
Published: June 2012

Background
—The role of a cluster of risk factors characteristic for the insulin resistance syndrome as a predictor for coronary heart disease (CHD) has not been studied previously.

Methods and Results
—Clustering of cardiovascular risk factors was analyzed by factor analysis to investigate whether these clusters (factors) predict CHD events (CHD death or nonfatal myocardial infarction) in a nondiabetic population of 1069 subjects 65 to 74 years old from eastern Finland followed up for 7 years. There were 151 CHD events (92 for men, 59 for women) during the follow-up period. In men, factor 1 (the insulin resistance factor, which reflected primarily body mass index, waist-to-hip ratio, triglycerides, fasting plasma glucose, and insulin) (hazards ratio [HR] with 95% CI, 1.33, CI 1.08, 1.65,
P
=0.008), factor 2 (alcohol consumption, high HDL cholesterol, low triglycerides) (HR 0.78, CI 0.63, 0.96,
P
=0.020), factor 3 (age, systolic blood pressure, urinary albumin/creatinine ratio, left ventricular hypertrophy) (HR 1.52, CI 1.26, 1.83,
P
<0.001), and factor 4 (high total cholesterol and triglycerides) (HR 1.42, CI 1.15, 1.77,
P
=0.002) predicted CHD events in multivariate Cox regression analysis. In women, the insulin resistance factor did not predict CHD events (HR 1.06, CI 0.82, 1.36), but factor 2 (previous stroke, low HDL cholesterol and high triglycerides) (HR 1.34, CI 1.06, 1.69,
P
=0.014) and factor 3 (age, systolic blood pressure, urinary albumin/creatinine ratio, left ventricular hypertrophy) (HR 1.44, CI 1.15, 1.82,
P
=0.002) predicted CHD events.

Conclusions
—Our study supports the notion that the insulin resistance syndrome is a risk factor for CHD in elderly men.
Increased Incidence of Periprocedural Complications Among Patients With Peripheral Vascular Disease Undergoing Myocardial Revascularization in the Bypass Angioplasty Revascularization Investigation
Authors: Rihal Charanjit S. , Sutton-Tyrrell Kim , Guo Ping , Keller Norma M. , Jandova Ruzena , Sellers Mary Ann , Schaff Hartzell V. , Holmes David R.
Published: June 2012

Background
—Risks of coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) may be different in the presence of peripheral vascular disease (PVD).

Methods and Results
—We analyzed outcomes of 550 patients with PVD enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry. Compared with 1770 patients without PVD, those with PVD were older and had a greater prevalence of medical comorbid conditions. No significant differences in coronary anatomy or PTCA success rates were found. The risk of any major complication (death, myocardial infarction, stroke, coma, or emergency revascularization) after PTCA was significantly higher among patients with PVD (11.7% versus 7.8%,
P
=0.027). In multivariate analysis, this represented a 50% increase in the odds of having any major complication (multivariate odds ratio, 1.5;
P
=0.032). Among patients undergoing CABG, the risk of major complications was found to be markedly higher for patients with PVD (12%) than those without (6.1%,
P
=0.003) even after controlling for baseline differences (multivariate odds ratio, 1.8;
P
=0.018). Major differences between the PTCA and CABG groups were related primarily to a higher risk of neurological complications in PVD patients who had CABG (multivariate odds ratio, 2.8;
P
<0.001).

Conclusions
—We conclude that patients with PVD are at high risk for periprocedural complications after myocardial revascularization, in particular neurological events.
Extracardiac Ablation of the Canine Atrioventricular Junction by Use of High-Intensity Focused Ultrasound
Authors: Strickberger S. Adam , Tokano Takashi , Kluiwstra Jan-Ulco A. , Morady Fred , Cain Charles
Published: June 2012

Background
—High-intensity focused ultrasound has been applied to internal organs from outside the body to ablate tissue. No published study has assessed the feasibility of ablating cardiac tissue within the beating heart by use of this type of therapeutic ultrasound. The purpose of this study was to determine whether high-intensity focused ultrasound can be used to ablate the atrioventricular (AV) junction within the beating heart.

Methods and Results
—Ten dogs were anesthetized and underwent a thoracotomy. The heart was covered with a polyvinyl chloride membrane. The thorax above the membrane was perfused with degassed water, which functioned as a coupling medium for the ultrasound. A 7.0-MHz diagnostic ultrasound probe was affixed to a spherically focused 1.4-MHz high-intensity focused ultrasound transducer with a 1.1×8.3-mm focal zone 63.5 mm from the ablation transducer. The diagnostic ultrasound probe was calibrated such that the location of the focal zone of the ablation transducer was identifiable on the 2-dimensional ultrasound image. Target sites were identified with the diagnostic ultrasound. The maximum ultrasound intensity for ablation (2.8 kW/cm
2
) was delivered to the AV junction only during electrical diastole and for a total of 30 seconds. Complete AV block was achieved in each of the 10 dogs with 6.5±5.6 (range, 3 to 21) 30-second applications of therapeutic ultrasound. Gross inspection showed that the mean lesion volume was 124±143 mm
3
, with a depth of 6.7±3.6 mm, a length of 5.7±2.5 mm, and a width of 4.7±1.8 mm. Four hours after the dogs were killed, histopathological study demonstrated a well-demarcated area of necrosis and early inflammation.

Conclusions
—High-intensity focused ultrasound produces well-demarcated lesions and appears to be a feasible energy source to create complete AV block within the beating heart without damaging the overlying or underlying cardiac tissue. This energy source may allow for a noninvasive approach to ablation of cardiac arrhythmias.
Early Dipyridamole
99m
Tc-Sestamibi Single Photon Emission Computed Tomographic Imaging 2 to 4 Days After Acute Myocardial Infarction Predicts In-Hospital and Postdischarge Cardiac Events
Authors: Brown Kenneth A. , Heller Gary V. , Landin Ronald S. , Shaw Leslee J. , Beller George A. , Pasquale Michael J. , Haber Stephen B.
Published: June 2012

Background
—Because of its brief hemodynamic effects and minor effect on determinants of myocardial oxygen demand, vasodilator stress myocardial perfusion imaging (MPI) can be applied very early after acute myocardial infarction (AMI) for risk stratification, allowing management decisions to be made earlier and thus potentially shortening hospitalization stays, reducing costs, and preventing early cardiac events. This multicenter randomized trial compared the prognostic value of early dipyridamole MPI and standard predischarge submaximal exercise MPI in patients who presented with AMI.

Methods and Results
—Patients who presented with their first AMI (n=451) were randomized in a 3:1 ratio to undergo either both an early (day 2 to 4) dipyridamole
99m
Tc-sestamibi MPI study and a predischarge (day 6 to 12) submaximal exercise
99m
Tc-sestamibi MPI study or only the predischarge study. Multivariate predictors of in-hospital cardiac events included nuclear imaging summed stress and summed reversibility scores and peak creatine kinase. For postdischarge cardiac events, multivariate predictors in patients undergoing dipyridamole MPI included only the summed stress, reversibility, and rest imaging scores and anterior MI. For a given summed stress score, the interaction of reversibility score further improved the predictive value. Dipyridamole MPI showed better risk stratification than submaximal exercise MPI.

Conclusions
—Dipyridamole MPI very early after MI predicts early and late cardiac events, with superior prognostic value compared with submaximal exercise imaging. The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent MI. This technique can allow management decisions to be made earlier with regard to AMI patients and could have important economic impact if applied widely.
Joint Effects of an Aldosterone Synthase (CYP11B2) Gene Polymorphism and Classic Risk Factors on Risk of Myocardial Infarction
Authors: Hautanen Aarno , Toivanen Petri , Mänttäri M. , Tenkanen Leena , Kupari Markku , Manninen V. , Kayes Kathleen M. , Rosenfeld Scott , White Perrin C.
Published: June 2012

Background
—The −344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI.

Methods and Results
—We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men. There was a nonsignificant trend of increasing risk of MI with number of copies of the −344C allele. However, this allele was associated in a gene dosage–dependent manner with markedly increased MI risk conferred by classic risk factors. Whereas smoking conferred a relative risk of MI of 2.50 (
P
=0.0001) compared with nonsmokers in the entire study population, the relative risk increased to 4.67 in −344CC homozygous smokers (relative to nonsmokers with the same genotype,
P
=0.003) and decreased to 1.09 in −344TT homozygotes relative to nonsmokers with this genotype. Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors.

Conclusions
—Smoking and dyslipidemia are more potent risk factors for nonfatal MI in males who have the −344C allele of CYP11B2.
Frequency of Early Occlusion and Stenosis in a Left Internal Mammary Artery to Left Anterior Descending Artery Bypass Graft After Surgery Through a Median Sternotomy on Conventional Bypass
Authors: Berger Peter B. , Alderman Edwin L. , Nadel Andrea , Schaff Hartzell V.
Published: June 2012

Background
—Uncertainty exists regarding the frequency of early occlusion when the left internal mammary artery (LIMA) is anastomosed to the left anterior descending artery (LAD) through a sternotomy with conventional coronary artery bypass grafting (CABG). The issue has gained importance for comparison with less invasive surgical approaches in which operative exposure may be limited and graft anastomosis more difficult.

Methods and Results
—Data were analyzed from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial in which 617 patients underwent conventional CABG of the LAD with a LIMA between April 1993 and May 1995. Coronary angiography was performed a mean of 10.8 days postoperatively. Patients were randomized to receive intraoperative aprotinin, an inhibitor of several serine proteinases, or placebo. Because no differences existed in patency rates of LIMA grafts between patients who received aprotinin and placebo, both groups were analyzed collectively. On coronary angiography, the LIMA was widely patent (<50% stenosis) in 561 patients (91%), had ≥50% and <99% stenosis in 48 patients (7.8%), and was occluded in 8 patients (1.3%). Therefore, the LIMA was patent in 609 patients (98.7%).

Conclusions
—In the IMAGE trial, the largest and most contemporary early angiographic analysis of CABG available, early patency of the LIMA was >98% when anastomosed to the LAD. These data provide an important benchmark for less invasive surgical approaches in which the LIMA is anastomosed to the LAD.
Pharmacology and Biological Efficacy of a Recombinant, Humanized, Single-Chain Antibody C5 Complement Inhibitor in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass
Authors: Fitch Jane C. K. , Rollins Scott , Matis Louis , Alford Bernadette , Aranki Sary , Collard Charles D. , Dewar Michael , Elefteriades John , Hines Roberta , Kopf Gary , Kraker Philip , Li Lan , O’Hara Ruth , Rinder Christine , Rinder Henry , Shaw Richard , Smith Brian , Stahl Gregory , Shernan Stanton K.
Published: June 2012

Background
—Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB.

Methods and Results
—A humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced (
P
<0.05) in patients who received 1 and 2 mg/kg. There was a 40% reduction in myocardial injury (creatine kinase–MB release,
P
=0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (
P
<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (
P
<0.05) in patients who received 1 or 2 mg/kg.

Conclusions
—A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.
Reversal by Vasopressin of Intractable Hypotension in the Late Phase of Hemorrhagic Shock
Authors: Morales David , Madigan John , Cullinane Suzanne , Chen Jonathan , Heath Mark , Oz Mehmet , Oliver Juan A. , Landry Donald W.
Published: June 2012

Background
—Hypovolemic shock of marked severity and duration may progress to cardiovascular collapse unresponsive to volume replacement and drug intervention. On the basis of clinical observations, we investigated the action of vasopressin in an animal model of this condition.

Methods and Results
—In 7 dogs, prolonged hemorrhagic shock (mean arterial pressure [MAP] of ≈40 mm Hg) was induced by exsanguination into a reservoir. After ≈30 minutes, progressive reinfusion was needed to maintain MAP at ≈40 mm Hg, and by ≈1 hour, despite complete restoration of blood volume, the administration of norepinephrine ≈3 μg · kg
−1
· min
−1
was required to maintain this pressure. At this moment, administration of vasopressin 1 to 4 mU · kg
−1
· min
−1
increased MAP from 39±6 to 128±9 mm Hg (
P
<0.001), primarily because of peripheral vasoconstriction. In 3 dogs subjected to similar prolonged hemorrhagic shock, angiotensin II 180 ng · kg
−1
· min
−1
had only a marginal effect on MAP (45±12 to 49±15 mm Hg). Plasma vasopressin was markedly elevated during acute hemorrhage but fell from 319±66 to 29±9 pg/mL before administration of vasopressin (
P
<0.01).

Conclusions
—Vasopressin is a uniquely effective pressor in the irreversible phase of hemorrhagic shock unresponsive to volume replacement and catecholamine vasopressors. Vasopressin deficiency may contribute to the pathogenesis of this condition.
Novel Therapeutic Strategy Against Central Baroreflex Failure
Authors: Sato Takayuki , Kawada Toru , Shishido Toshiaki , Sugimachi Masaru , Alexander Joe , Sunagawa Kenji
Published: June 2012

Background
—Central baroreflex failure in Shy-Drager syndrome and traumatic spinal cord injuries results in severe orthostatic hypotension and often confines the patient to the bed. We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial feedback control system able automatically to regulate sympathetic vasomotor tone, that is, a bionic baroreflex system (BBS). With the use of a rat model of central baroreflex failure, we developed the BBS and tested its efficacy.

Methods and Results
—Our prototype BBS for the rat consisted of a pressure sensor placed into the aortic arch, stimulation electrodes implanted into the greater splanchnic nerve, and a computer-driven neural stimulator. By a white noise approach for system identification, we first estimated the dynamic properties underlying the normal baroreflex control of systemic arterial pressure (SAP) and then determined how the BBS computer should operate in real time as the artificial vasomotor center to mimic the dynamic properties of the native baroreflex. The open-loop transfer function of the artificial vasomotor center was identified as a high-pass filter with a corner frequency of 0.1 Hz. We evaluated the performance of the BBS in response to rapid-progressive hypotension secondary to sudden sympathetic withdrawal evoked by the local imposition of a pressure step on carotid sinus baroreceptors in 16 anesthetized rats. Without the BBS, SAP rapidly fell by 49±8 mm Hg in 10 seconds. With the BBS placed on-line with real-time execution, the SAP fall was suppressed by 22±6 mm Hg at the nadir and by 16±5 mm Hg at the plateau. These effects were statistically indistinguishable from those of the native baroreflex system.

Conclusions
—These results suggest the feasibility of a BBS approach for central baroreflex failure.
Simultaneous Multisite Mapping of the Right and the Left Atrial Septum in the Canine Intact Beating Heart
Authors: Sun Huabin , Velipasaoglu Emre O. , Wu David E. , Kopelen Helen A. , Zoghbi William A. , Spencer William H. , Khoury Dirar S.
Published: June 2012

Background
—The spread of activation between the right atrium (RA) and left atrium (LA), particularly along the right and left aspects of the interatrial septum, is not clear.

Methods and Results
—Basket-shaped catheters carrying 64 electrodes were deployed into both the RA and LA of 10 dogs. Position and orientation of the baskets were determined by fluoroscopy and echocardiography. Basket unipolar electrograms were simultaneously recorded in each dog during sinus rhythm, right ventricular pacing, and pacing of the right septum through the basket in the superior and inferior regions. Isochrone maps depicting all aspects of the atria, including the septum, were compared. During sinus rhythm and superior right septal pacing, wave fronts propagated predominantly from superior to inferior regions on both the right and left septum. However, activation of the left septum was delayed compared with the right septum. During right ventricular pacing and inferior right septal pacing, activation of the septum was discordant; 1 wave front propagated rapidly on the right septum from inferior to superior regions, whereas 2 opposing wave fronts originated on the left septum in both the superior and inferior regions. The left septum was activated predominantly by the superior wave front. Activation of the left septum was completed in a significantly shorter time during pacing of the right septum in the inferior region compared with the superior region.

Conclusions
—In dogs, activation of the right and left aspects of the interatrial septum is discordant. Electrical connections are present between the RA and LA in regions superior as well as inferior to the septum.
New Device for Closure of Muscular Ventricular Septal Defects in a Canine Model
Authors: Amin Zahid , Gu Xiaoping , Berry James M. , Bass John L. , Titus Jack L. , Urness Myra , Han Young-Min , Amplatz Kurt
Published: June 2012

Background
—Repair of muscular ventricular septal defects (MVSDs) has always been challenging to the surgeon. Long-term morbidity and mortality are significantly increased if the defects are closed via left ventriculotomy or if they are associated with other complex congenital anomalies. The purpose of this study was to close MVSDs with the Amplatz ventricular septal defect device. This device is constructed from 0.004-in nitinol wire mesh filled with polyester fibers. It is retrievable, repositionable, self-centering, and of low profile.

Methods and Results
—MVSDs were created with the help of a sharp punch in 10 dogs. The location of the defects was anterior muscular (n=3), midmuscular (n=3), apical (n=3), and inlet muscular (n=1). The diameter of the defects ranged from 6 to 14 mm. All defects were closed in the catheterization laboratory. The device was placed with the help of transesophageal echocardiography and fluoroscopy. A 7F sheath was used to deploy the device from the right ventricular side in 8 and the left ventricular side in 2 dogs. Placement was successful in all animals. The complete closure rate was 30% (3/10) immediately after placement and 100% at 1-week follow-up. Pathological examination of the heart revealed complete endothelialization of the device in dogs killed after 3 months.

Conclusions
—The Amplatz ventricular septal defect device appears highly efficacious in closing MVSDs. The advantages include a small delivery sheath, complete retrievability before release, and the fact that it is self-centering and self-expanding, thereby making it an attractive option in smaller children.
Baroreflex Gain Predicts Blood Pressure Recovery During Simulated Ventricular Tachycardia in Humans
Authors: Hamdan Mohamed H. , Joglar Jose A. , Page Richard L. , Zagrodzky Jason D. , Sheehan Clifford J. , Wasmund Stephen L. , Smith Michael L.
Published: June 2012

Background
—Despite similar degrees of left ventricular dysfunction and similar tachycardia or pacing rate, blood pressure (BP) response and symptoms vary greatly among patients. Sympathetic nerve activity (SNA) increases during sustained ventricular tachycardia (VT), and the magnitude of this sympathoexcitatory response appears to contribute to the net hemodynamic outcome. We hypothesize that the magnitude of sympathoexcitation and thus arterial baroreflex gain is an important determinant of the hemodynamic outcome of VT.

Methods and Results
—We evaluated the relation between arterial baroreflex sympathetic gain and BP recovery during rapid ventricular pacing (VP) in patients referred for electrophysiological study. Efferent postganglionic muscle SNA, BP, and central venous pressure (CVP) were measured in 14 patients during nitroprusside infusion and during VP at 150 (n=12) or 120 (n=2) bpm. Arterial baroreflex gain was defined as the slope of the relationship of change in SNA to change in diastolic BP during nitroprusside infusion. Recovery of mean arterial pressure (MAP) during VP was measured as the increase in MAP from the nadir at the onset of pacing to the steady-state value during sustained VP. Arterial baroreflex gain correlated positively with recovery of MAP (
r
=0.57,
P
=0.034). No significant correlation between ejection fraction and baroreflex gain (
r
=0.48,
P
=0.08) or BP recovery (
r
=0.41,
P
=0.15) was found. When patients were separated into high versus low baroreflex gain, the recovery of MAP during simulated VT was significantly greater in patients with high gain.

Conclusions
—These data strongly suggest that arterial baroreflex gain contributes significantly to hemodynamic stability during simulated VT. Knowledge of baroreflex gain in individual patients may help the clinician tailor therapy directed toward sustained VT.
Atrial Linear Ablations in Pigs
Authors: Gepstein Lior , Hayam Gal , Shpun Shlomo , Cohen David , Ben-Haim Shlomo A.
Published: June 2012

Background
—Generation of long and continuous linear ablations is required in a growing number of atrial arrhythmias. However, deployment and assessment of these lesions may be difficult, and there are few data regarding their short- and long-term effects on atrial electrophysiology and pathology.

Methods and Results
—A nonfluoroscopic mapping and navigation technique was used to generate 3-dimensional (3D) electroanatomic maps of the right atrium in 8 pigs. The catheter was then used to deliver sequential radiofrequency (RF) applications (power output gradually increased until 80% reduction in the amplitude of the unipolar electrogram) to generate a continuous lesion between the superior and inferior venae cavae. The animals were remapped 4 weeks after ablation during septal pacing. Lesion continuity was confirmed in all cases by the following criteria: (1) activation maps indicating conduction block [significant disparities in activation times (52.0±16.0 ms) and opposite orientation of the activation wave front on opposing sides of the lesion], (2) evidence of double potentials (interspike time difference of 52.3±17.1 ms), and (3) low peak-to-peak amplitude of the bipolar electrograms (0.7±0.6 mV) along the lesion. At autopsy, all lesions were continuous and transmural, averaged 50.5±6.7 mm, and were characterized histologically by transmural fibrosis throughout the length of the lesion.

Conclusions
—Long linear atrial ablation, created by sequential RF applications (using unipolar amplitude attenuation as the end point for energy delivery), results in long-term continuous and transmural lesions. Lesion continuity is associated with evidence of conduction block in the 3D activation maps and the presence of double potentials and low electrogram amplitude along the lesion.
Platelet Glycoprotein IIb/IIIa Antagonists
Authors: Scarborough Robert M. , Kleiman Neal S. , Phillips David R.
Published: June 2012

Abstract
—During the last decade, intensive efforts have been made to evaluate the role of the platelet glycoprotein (GP) IIb/IIIa complex in platelet-mediated thrombus formation. Significant efforts have also been made to design potent antagonists of this “final common pathway” of platelet aggregation to be used as novel therapeutic strategies to treat acute coronary syndromes. Although several different GP IIb/IIIa antagonists have convincingly demonstrated the usefulness of this platelet-directed therapeutic strategy, a number of lingering unsolved and sometimes misunderstood issues concerning the pharmacology and optimal clinical usefulness of these agents remain to be explored. This article reviews these issues, which include antagonist affinity, reversibility, and receptor specificity. Other issues are related to the effects of GP IIb/IIIa receptor availability, neoepitopes induced by antagonist binding with the potential to mediate thrombocytopenia, optimal methods of platelet monitoring and, perhaps ultimately, the potential therapeutic index of the oral class of GP IIb/IIIa antagonists. All of these specific issues are likely to be illuminated in the next several years, which will greatly determine the breadth of this therapeutic class.
Asymmetry of Right Ventricular Enlargement in Response to Tricuspid Regurgitation
Authors: Reynertson Sandra I. , Kundur Ramesh , Mullen G. Martin , Costanzo Maria Rosa , McKiernan Thomas L. , Louie Eric K.
Published: June 2012

Background
—Analysis of right ventricular adaptation to tricuspid regurgitation was studied in 10 heart transplant recipients following inadvertent endomyocardial biopsy disruption of the tricuspid apparatus.

Methods and Results
—Echocardiography demonstrated progressive diastolic right ventricular cavity enlargement (19.5±5.0 to 30.3±5.4 cm
2
,
P
<0.0002), with disproportionate elongation along the midminor axis (3.5±0.6 to 5.0±0.5 cm,
P
<0.001). As the right ventricle remodeled to more spherical (and less elliptical) proportions, the end-diastolic right ventricular midminor axis/long axis ratio increased significantly from 0.52±0.10 to 0.68±0.07,
P
<0.005.

Conclusions
—Ventricular enlargement due to right ventricular volume overload results in disproportionate dilation along the free wall to septum minor axis.
Relation of the Contractile Reserve of Hibernating Myocardium to Myocardial Structure in Humans
Authors: Nagueh Sherif F. , Mikati Issam , Weilbaecher Donald , Reardon Michael J. , Al-Zaghrini Ghassan J. , Cacela Duarte , He Zuo-Xiang , Letsou George , Noon George , Howell Jimmy F. , Espada Rafael , Verani Mario S. , Zoghbi William A.
Published: June 2012

Background
—Although dobutamine echocardiography (DE) is widely used to assess myocardial viability in humans, little is known about the relation between contractile reserve and myocardial structure.

Methods and Results
—We evaluated 20 patients with coronary disease (64±13 years old, ejection fraction 28±7.5%) with DE (up to 40 μg · kg
−1
· min
−1
), rest-redistribution
201
Tl single photon emission CT, and quantitative angiography before bypass surgery. During surgery, patients underwent transmural myocardial biopsies (n=37) guided by transesophageal echocardiography to determine the extent of interstitial fibrosis and intracellular and interstitial proteins by histopathology and immunohistochemistry. Among the 37 segments biopsied, 16 recovered function as assessed 2 to 3 months later. Segments with postoperative functional recovery had more wall thickening at low-dose DE (28% versus 3%,
P
<0.001), higher thallium uptake (69% versus 48%,
P
=0.03), and less interstitial fibrosis (2% versus 28%,
P
<0.001). Quantitative angiographic parameters did not predict recovery of function. Segments with DE viability (contractile reserve and/or ischemia) had less fibrosis (2.7% versus 28%,
P
<0.001), less vimentin and fibronectin (both
P
<0.01), more glycogen (
P
=0.016), and higher thallium uptake (64% versus 35.5%,
P
<0.05) than those without viability. Viable segments by both DE and thallium had less fibrosis (1%) than those viable by 1 of the 2 techniques (9%) or not viable by both (28%,
P
=0.005). Thickening at low-dose DE correlated well with the extent of interstitial fibrosis (
r
=−0.83,
P
<0.01).

Conclusions
—Contractile reserve during DE correlates inversely with the extent of interstitial fibrosis and the amount of fibronectin and vimentin and directly with rest-redistribution thallium uptake.
Diagnostic and Prognostic Value of Serial Dobutamine Stress Echocardiography for Noninvasive Assessment of Cardiac Allograft Vasculopathy
Authors: Spes Christoph H. , Klauss Volker , Mudra Harald , Schnaack Susanne D. , Tammen Andres R. , Rieber Johannes , Siebert Uwe , Henneke Karl-Heinz , Überfuhr Peter , Reichart Bruno , Theisen Karl , Angermann Christiane E.
Published: June 2012

Background
—Routine methods for surveillance of cardiac allograft vasculopathy (CAV) are coronary angiography and intravascular ultrasound (IVUS). This study analyzed the diagnostic and prognostic value of dobutamine stress echocardiography (DSE) for noninvasive assessment of CAV.

Methods and Results
—In 109 heart transplant recipients, 333 DSEs were compared with 285 coronary angiograms and 199 IVUS analyses. Studies were repeated after 1, 2, 3, 4, and ≥5 years in 88, 74, 37, 18, and 7 patients, respectively. Resting 2D echocardiography detected CAV defined by IVUS and angiography with a sensitivity of 57% (specificity 88%). DSE increased the sensitivity to 72% (
P
=0.002). M-mode analysis increased the sensitivity of 2D rest and stress analysis (
P
=0.001, 0.004). Cardiac events occurred after 1.9% of normal stress tests by 2D analysis (combined 2D and M-mode: 0%), compared with 6.3% (3.8%) of normal resting studies. Worsening of serial DSE indicated an increased risk of events compared with no deterioration (relative risk 7.26,
P
=0.0014). Serial deterioration detected by stress only was associated with a higher risk of events than changes evident from resting studies (relative risk 3.06,
P
=0.0374).

Conclusions
—DSE identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies. The prognostic value of DSE is comparable to that of IVUS and angiography.
Protective Effects of Preconditioning in Cultured Rat Endothelial Cells
Authors: Beauchamp Philippe , Richard Vincent , Tamion Fabienne , Lallemand Françoise , Lebreton Jean-Pierre , Vaudry Hubert , Daveau Maryvonne , Thuillez Christian
Published: June 2012

Background
—Preconditioning with brief periods of ischemia protects the coronary endothelium against acute and chronic reperfusion injury, but the mechanisms of this endothelial protection remain unknown. We hypothesized that preconditioning protects endothelial cells through a decreased production of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), leading to a lesser adhesion of neutrophils to the endothelium.

Methods and Results
—Cultured rat aortic endothelial cells were subjected to 6-hour anoxia followed by various durations of reoxygenation. Preconditioning was induced by 1-hour anoxia and 1-hour reoxygenation. ICAM-1 gene expression was measured by polymerase chain reaction, and the percentage of cells expressing ICAM-1 was assessed by confocal laser fluorescence microscopy. Anoxia/reoxygenation increased expression of ICAM-1, with a peak occurring after 6 hours of reoxygenation for mRNA and 9 hours for protein. Preconditioning prevented the increase in ICAM-1. Similar reductions were observed with the free radical scavenger N-2 mercaptopropionyl glycine (MPG). The inhibitory effect of preconditioning on ICAM-1 expression was abolished by an inhibitor of protein kinase C, an inhibitor of nitric oxide synthesis, and by MPG but was not affected by an adenosine receptor antagonist. Finally, both preconditioning and MPG partially prevented the increased adhesion of human neutrophils to reoxygenated endothelial cells.

Conclusions
—Preconditioning prevented reoxygenation-induced, free radical–mediated expression of ICAM-1 by a mechanism involving activation of protein kinase C and production of nitric oxide and free radicals, and this is associated with a lesser adhesion of neutrophils to endothelial cells. Such prevention of neutrophil adhesion may contribute to the protective effect of preconditioning against reperfusion-induced endothelial injury.
Living Anatomy of the Atrioventricular Junctions. A Guide to Electrophysiologic Mapping
Authors: Cosío Francisco G. , Anderson Robert H. , Kuck Karl-Heinz , Becker Anton , Borggrefe Martin , Campbell Ronald W. F. , Gaita Fiorenzo , Guiraudon Gerard M. , Haïssaguerre Michel , Rufilanchas Juan J. , Thiene Gaetano , Wellens Hein J. J. , Langberg Jonathan , Benditt David G. , Bharati Saroja , Klein George , Marchlinski Francis , Saksena Sanjeev
Published: June 2012

Abstract
—Current nomenclature for the atrioventricular (AV) junctions derives from a surgically distorted view, placing the valvar rings and the triangle of Koch in a single plane with antero-posterior and right-left lateral coordinates. Within this convention, the aorta is considered to occupy an anterior position, although the mouth of the coronary sinus is shown as being posterior. Although this nomenclature has served its purpose for the description and treatment of arrhythmias dependent on accessory pathways and atrioventricular nodal reentry, it is less than satisfactory for the description of atrial and ventricular mapping. To correct these deficiencies, a consensus document has been prepared by experts from the Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. It proposes a new anatomically sound nomenclature that will be applicable to all chambers of the heart. In this report, we discuss its value for description of the AV junctions, establishing the principles of this new nomenclature.
Stimulation of Fecal Steroid Excretion After Infusion of Recombinant Proapolipoprotein A-I
Authors: Eriksson Mats , Carlson Lars A. , Miettinen Tatu A. , Angelin Bo
Published: June 2012

Background
—Apolipoprotein (apo) A-I is the major protein component of HDL, a cholesterol transport particle that protects against atherosclerosis. Apo A-I is believed to promote reverse cholesterol transport, transferring cholesterol from peripheral cells to the liver for subsequent elimination. To test this hypothesis in humans, we measured fecal steroid excretion before and after the intravenous infusion of human proapo A-I (precursor of apo A-I) liposome complexes.

Methods and Results
—Four subjects with heterozygous familial hypercholesterolemia were studied under standardized conditions. The fecal excretion of bile acids and neutral sterols was determined for 9 days before and 9 days after an intravenous infusion of recombinant human proapo A-I (4 g protein) liposome complexes. Plasma apoA-I and HDL cholesterol levels increased transiently (mean peak concentrations were 64% and 35% above baseline, respectively) during the first 24 hours. Mean lipoprotein lipid and apolipoprotein levels were not different during the 2 collecting periods, however. Serum lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, was also unchanged. The fecal excretion of cholesterol (neutral sterols and bile acids) increased in all subjects (mean increase, +39% and +30%, respectively), corresponding to the removal of ≈500 mg/d excess cholesterol after infusion. Control infusions with only liposomes in 2 of the patients did not influence lipoprotein pattern or cholesterol excretion.

Conclusions
—Infusion of proapoA-I liposomes in humans promotes net cholesterol excretion from the body, implying a stimulation of reverse cholesterol transport. This mechanism may prove useful in the treatment of atherosclerosis.
PREDICT: A Simple Risk Score for Clinical Severity and Long-Term Prognosis After Hospitalization for Acute Myocardial Infarction or Unstable Angina
Authors: Jacobs David R. , Kroenke Candyce , Crow Richard , Deshpande Mahesh , Gu Dong Feng , Gatewood Lael , Blackburn Henry
Published: June 2012

Background
—We evaluated short- and long-term mortality risks in 30- to 74-year-old patients hospitalized for acute myocardial infarction or unstable angina and developed a new score called PREDICT.

Methods and Results
—PREDICT was based on information routinely collected in hospital. Predictors abstracted from hospital record items pertaining to the admission day, including shock, heart failure, ECG findings, cardiovascular disease history, kidney function, and age. Comorbidity was assessed from discharge diagnoses, and mortality was determined from death certificates. For 1985 and 1990 hospitalizations, the 6-year death rate in 6134 patients with 0 to 1 score points was 4%, increasing stepwise to 89% for ≥16 points. Score validity was established by only slightly attenuated mortality prediction in 3570 admissions in 1970 and 1980. When case severity was controlled for, 6-year risk declined 32% between 1970 and 1990. When PREDICT was held constant, 24% of those treated with thrombolysis died in 6 years compared with 31% of those not treated.

Conclusions
—The simple PREDICT risk score was a powerful prognosticator of 6-year mortality after hospitalization.
Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina
Authors: Aukrust Pål , Müller Fredrik , Ueland Thor , Berget Trude , Aaser Elinor , Brunsvig Anne , Solum Nils Olav , Forfang Kolbjørn , Frøland Stig S. , Gullestad Lars
Published: June 2012

Background
—The CD40 ligand (CD40L) on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting plaque rupture in atheroma.

Methods and Results
—To study the role of CD40L-CD40 interaction in coronary disease, we analyzed levels of soluble (s) and membrane-bound CD40L in the peripheral blood from 29 patients with stable angina, 26 with unstable angina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with patients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor–agonist peptide SFLLRN in both patients and controls. (3) Platelets in patients with unstable angina were characterized ex vivo by decreased intracellular levels and decreased SFLLRN-stimulated release of sCD40L, which may possibly represent a higher percentage of degranulated platelets in these patients. (4) T cells in patients with unstable angina had enhanced surface expression of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulation in vitro when compared with patients with stable angina and controls. (5) Recombinant CD40L and serum from patients with unstable angina who had high sCD40L levels induced enhanced release of monocyte chemoattractant peptide-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis.

Conclusions
—This first demonstration of enhanced levels of soluble and membrane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and in the triggering and propagation of acute coronary syndromes.
Effects of β-Adrenergic Blocking Therapy on Left Ventricular Diastolic Relaxation Properties in Patients With Dilated Cardiomyopathy
Authors: Kim Michael H. , Devlin William H. , Das Sunil K. , Petrusha Janet , Montgomery Daniel , Starling Mark R.
Published: June 2012

Background
—The hemodynamic mechanism for the improvement in left ventricle (LV) end-diastolic pressure in cardiomyopathy patients treated with β-adrenergic blocking agents is controversial. We hypothesized that the salutary effect of this kind of therapy on LV end-diastolic pressure would be indicative of an improvement in late, passive diastolic relaxation properties.

Methods and Results
—We studied 14 cardiomyopathy patients in normal sinus rhythm with no arteriographic evidence of coronary artery disease and an LV ejection fraction of ≤40% by radionuclide angiography both before and after 6 months of metoprolol therapy with simultaneous micromanometry and biplane cineventriculography. Four comparable patients who were not treated with metoprolol were studied in a similar fashion and served as control subjects. In those receiving metoprolol, LV end-diastolic pressure decreased (
P
=0.001). The isovolumic relaxation index, τ
ln
, shortened (
P
=0.03). In a similar fashion, the LV chamber stiffness constant, κ, decreased (
P
=0.02), LV volume elastance improved (
P
=0.04), and the myocardial stiffness constant, κ
e
, decreased (
P
=0.02). A multiple regression analysis revealed that the decrease in LV end-diastolic pressure was indicative of significant improvements in τ
ln
and κ
e
with the relationship: LV end-diastolic pressure=−4.73+0.27 τ
ln
+0.54 κ
e
(
r
=0.81,
P
<0.0001). These LV diastolic relaxation properties did not change or worsened in the control cardiomyopathy patients.

Conclusions
—We conclude that the decrease in LV end-diastolic pressure in cardiomyopathy patients treated with metoprolol is an indicator of improvement in LV diastolic properties resulting from more complete myocardial relaxation.
Fetoscopic Transesophageal Electrocardiography and Stimulation in Fetal Sheep
Authors: Kohl Thomas , Kirchhof Paulus F. , Gogarten Wiebke , Reckers Julia , Asfour Boulos , Witteler Ralf , Haverkamp Wilhelm , Eckardt Lars , Marcus Abraham E. , VanAken Hugo , Breithardt Günter , Vogt Johannes , Scheld Hans H.
Published: June 2012

Background
—Therapy-refractory supraventricular tachycardia commonly results in hydrops and death in human fetuses. The purpose of this study in fetal sheep was to assess the feasibility of a minimally invasive fetoscopic approach for fetal transesophageal electrocardiography and stimulation aimed at diagnosis and termination of these tachycardias.

Methods and Results
—We studied a total of 10 fetal sheep (87 to 103 days of gestation; term=145 days). We entered the amniotic cavity using a percutaneous fetoscopic approach and placed various electrophysiology catheters into the fetal esophagus. We recorded the number of animals in which fetoscopic transesophageal electrocardiography and stimulation were successful and assessed pacing success and thresholds for different catheters. In addition, we monitored for potential adverse effects from stimulation and for other complications of the operation. Recording of transesophageal electrocardiograms was successful in all fetal sheep. Capture during stimulation was successfully documented by additional fetal bipolar surface electrocardiograms in 7 fetuses. In fetuses in which fetal surface electrocardiograms were not recorded, pacing stimulus artifacts interfered with documentation of capture. Although stimulation thresholds were high, the maternal rhythm was not affected by fetal stimulation.

Conclusions
—Fetoscopic fetal transesophageal electrocardiography and stimulation are feasible in fetal sheep. This minimally invasive approach might have the potential to improve diagnosis and management of therapy-refractory supraventricular tachycardias in human fetuses.