bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate Three-Dimensional Reconstruction of Intravascular Ultrasound Data
Authors: Evans James L. , Ng Kok-Hwee , Wiet Stephen G. , Vonesh Michael J. , Burns William B. , Radvany Martin G. , Kane Bonnie J. , Davidson Charles J. , Roth Sanford I. , Kramer Barry L. , Meyers Sheridan N. , McPherson David D.
Published: June 2012

Background
The geometrical accuracy of conventional three-dimensional (3D) reconstruction methods for intravascular ultrasound (IVUS) data (coronary and peripheral) is hampered by the inability to register spatial image orientation and by respiratory and cardiac motion. The objective of this work was the development of improved IVUS reconstruction techniques.

Methods and Results
We developed a 3D position registration method that identifies the spatial coordinates of an in situ IVUS catheter by use of simultaneous ECG-gated biplane digital cinefluoroscopy. To minimize distortion, coordinates underwent pincushion correction and were referenced to a standardized calibration cube. Gated IVUS data were acquired digitally, and the spatial locations of the imaging planes were matched to their corresponding coordinates. Image points were then transformed relative to their respective 3D coordinates, rendered in binary voxel format, resliced, and displayed on an image-processing workstation for off-line analysis. The method was tested by use of phantoms (straight tube, 360° circle, 240° spiral) and an in vitro coronary artery model. In vivo feasibility was assessed in patients who underwent routine interventional coronary procedures accompanied by IVUS evaluation. Actual versus calculated point locations were within 1.0±0.3 mm of each other (n=39). Calculated phantom volumes were within 4% of actual volumes. Phantom 3D reconstruction appropriately demonstrated complex morphology. Initial patient evaluation demonstrated method feasibility as well as errors if respiratory and ECG gating were not used.

Conclusions
These preliminary data support the use of this new method of 3D reconstruction of vascular structures with use of combined vascular ultrasound data and simultaneous ECG-gated biplane cinefluoroscopy.
Diagnostic Value of Echocardiography in Suspected Endocarditis
Authors: Lindner Jonathan R. , Case R. Alex , Dent John M. , Abbott Robert D. , Scheld W. Michael , Kaul Sanjiv
Published: June 2012

Background
We hypothesized that for the diagnosis of endocarditis, (1) transthoracic echocardiography (TTE) would be most valuable in patients with an intermediate clinical probability of the disease and (2) transesophageal echocardiography (TEE) would be most useful in patients with an intermediate probability when TTE either does not yield an adequate study or indicates an intermediate probability of endocarditis. We also sought to investigate the influence of echocardiographic results on antibiotic usage and its duration.

Methods and Results
TTE and TEE were performed in 105 consecutive patients with suspected endocarditis. Patients were classified as having either low, intermediate, or high probability of endocarditis on the basis of clinical criteria and separately on the basis of both TTE and TEE findings. TTE and TEE classified the majority (82% and 85%, respectively) of the 67 patients with a low clinical probability of endocarditis as having a low likelihood of the disease. Of the 14 patients with intermediate clinical probability, 12 had technically adequate TTE studies; 10 of these (83%) were classified as either high or low probability. All patients with intermediate clinical probability were classified as high or low probability by TEE. The majority of the 24 patients with high clinical probability were placed in the low-likelihood category by echocardiography (15 by TTE and 12 by TEE). There was concordance between TTE and TEE in 83% of all cases. TEE was useful for the diagnosis of endocarditis in patients with prosthetic valves and in those in whom TTE indicated an intermediate probability; these constituted <20% of patients in our study. The course of antibiotic therapy was influenced only by the clinical profile and not by the echocardiographic results.

Conclusions
Echocardiography should not be used to make a diagnosis of endocarditis in those with a low clinical probability of the disease. In those with an intermediate or high clinical probability, TTE should be the diagnostic procedure of choice. TEE for the diagnosis of endocarditis should be reserved only for patients who have prosthetic valves and in whom TTE is either technically inadequate or indicates an intermediate probability of endocarditis.
Initial Experience With an Implantable Hemodynamic Monitor
Authors: Steinhaus David M. , Lemery Robert , Bresnahan Dennis R. , Handlin Larry , Bennett Tom , Moore Alan , Cardinal Debbie , Foley Laura , Levine Richard
Published: June 2012

Background
Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure.

Methods and Results
The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52±16 mm Hg; diastolic, 29±11 mm Hg; and mean, 40±12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve.

Conclusions
Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.
Effects of Subtype-Selective and Balanced Angiotensin II Receptor Antagonists in a Porcine Coronary Artery Model of Vascular Restenosis
Authors: Huckle William R. , Drag Marlene D. , Acker Wayne R. , Powers Michele , McFall Rosemary C. , Holder Daniel J. , Fujita Tsuneo , Stabilito Inez I. , Kim Dooseop , Ondeyka Debra L. , Mantlo Nathan B. , Chang Raymond S.L. , Reilly Christopher F. , Schwartz Robert S. , Greenlee William J. , Johnson Jr Robert G.
Published: June 2012

Background
Numerous studies have demonstrated the ability of angiotensin II (Ang II) receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors to inhibit intimal hyperplasia after balloon dilatation of noncoronary arteries in small-animal models, suggesting an important role for Ang II in the response to injury. Although ACE inhibitors have not been similarly effective in nonhuman coronary models or in human restenosis trials, questions remain regarding the efficacy of ACE inhibitors against tissue ACE and the contributions of ACE-independent pathways of Ang II generation. Unlike ACE inhibitors, Ang II receptor antagonists have the potential to inhibit responses to Ang II independent of its biosynthetic origin.

Methods and Results
In separate studies, three Ang II receptor antagonists, including AT
1
-selective (L-158,809), balanced AT
1
/AT
2
(L-163,082), and AT
2
-selective (L-164,282) agents, were evaluated for their ability to inhibit vascular intimal thickening in a porcine coronary artery model of vascular injury. Preliminary studies in a rat carotid artery model revealed that constant infusion of L-158,809 (0.3 or 1.0 mg·kg
−1
·d
−1
) reduced the neointimal cross-sectional area by up to 37% measured 14 days after balloon dilatation. In the porcine studies, animals were treated with vehicle or test compound beginning 2 days before and extending 28 days after experimental angioplasty. Left anterior descending, left circumflex, and/or right coronary arteries were injured by inflation of commercially available angioplasty balloons with placement of coiled metallic stents. Infusion of L-158,809 (1 mg·kg
−1
·d
−1
), L-163,082 (1 mg·kg
−1
·d
−1
), or L-164,282 (1.5 mg·kg
−1
·d
−1
) in the study animals yielded plasma drug levels sufficient either to chronically block or, for L-164,282, to spare pressor responses to exogenous Ang II. Neither L-158,809, L-163,082, nor L-164,282 had statistically significant effects (
P
=.12,
P
=.75, and
P
=.48, respectively, compared with vehicle-treated controls) on neointimal thickness (normalized for degree of injury) measured by morphometric analysis at day 28 after angioplasty.

Conclusions
These findings indicate that chronic blockade of Ang II receptors by either site-selective or balanced AT
1
/AT
2
antagonists is insufficient to inhibit intimal hyperplasia after experimental coronary vascular injury in the pig. The results further suggest that, unlike in the rat carotid artery, Ang II is not a major mediator of intimal thickening in the pig coronary artery.
Contribution of Muscle Afferents to the Hemodynamic, Autonomic, and Ventilatory Responses to Exercise in Patients With Chronic Heart Failure
Authors: Piepoli Massimo , Clark Andrew L. , Volterrani Maurizio , Adamopoulos Stamatis , Sleight Peter , Coats Andrew J.S.
Published: June 2012

Background
A neural linkage between peripheral abnormalities and the exaggerated exercise responses in chronic heart failure (CHF) was postulated. We studied the ergoreceptors (afferents sensitive to skeletal muscle work) in CHF and whether training can affect their activity.

Methods and Results
In 12 stable CHF patients (ejection fraction [EF]=26.4%) and 10 control subjects (EF=55.3%), we compared the responses to dynamic handgrip and during a 3-minute period of posthandgrip regional circulatory occlusion (PH-RCO). The ergoreflex contribution was quantified as the percentage responses to exercise maintained by PH-RCO compared with recovery without PH-RCO. Patients showed ergoreflex overactivation compared with control subjects in terms of ventilation (86.5% versus 54.5%), diastolic pressure (97.8% versus 53.5%), and leg vascular resistance (108.1% versus 48.9%) (all
P
<.05). The contribution of the ergoreflex to vagal withdrawal (high frequency of RR variability) and sympathetic activation (low frequency of RR, pressure variability) was evident in both groups. Nine control subjects and nine CHF patients participated in 6 weeks of forearm training. Training reduced the ergoreflex contributions more in CHF than in control subjects: diastolic pressure (−33.2% versus −4.6%), ventilation (−57.6% versus −24.6%), and leg vascular resistance (−59.9% versus −8.0%) (all
P
<.05).

Conclusions
(1) The ergoreflex role has a larger effect on the responses to exercise in CHF than in control subjects. (2) Training may reduce this exaggerated ergoreflex activity, thereby improving the responses to exercise.
Risk Factors for Syncope Recurrence After a Positive Tilt-Table Test in Patients With Syncope
Authors: Sheldon Robert , Rose Sarah , Flanagan Patricia , Koshman Mary Lou , Killam Shawn
Published: June 2012

Background
Recent work with head-up tilt-table testing has suggested that many patients with syncope may have recurrent neurally mediated episodes of bradycardia, hypotension, or both. The purpose of this study was to determine how to identify patients at high risk of a recurrence of neuromediated syncope after a positive isoproterenol/tilt-table test.

Methods and Results
A cohort of 101 drug-free patients in a university hospital outpatient clinic with syncope and a positive isoproterenol/tilt-table test underwent baseline assessment of demographic variables, symptomatic burden, and hemodynamic and clinical responses to tilt testing. The primary outcome measure was the time to the first recurrent syncopal spell. The actuarial probabilities of remaining syncope free after 1 and 2 years were 72% and 60%, respectively. Multivariate proportional hazards analysis demonstrated that the most powerful predictor of a recurrence of syncope was the logarithm of the number of preceding syncopal spells (
P
<.001). Other predictive variables included the duration of syncopal symptoms, tilt-test symptomatic outcome, and trough heart rate. The probability of a recurrence of syncope also varied with the logarithm of the frequency of preceding spells (
P
=.008). The median frequency of pretest spells was 0.3/month; after the tilt test, the median frequency dropped ≈90% to 0.03 per month.

Conclusions
The risk of a recurrence of syncope after a positive tilt-table test can be predicted with simple pretest and intratest variables.
Thermal Latency in Radiofrequency Ablation
Authors: Wittkampf Fred H.M. , Nakagawa Hiroshi , Yamanashi William S. , Imai Shinobu , Jackman Warren M.
Published: June 2012

Background
Progression of unintentionally induced atrioventricular delay is occasionally observed directly after termination of radiofrequency delivery in the vicinity of the atrioventricular node. We postulated that the application of a radiofrequency pulse may result in a tissue temperature rise that continues after the pulse.

Methods and Results
Using the thigh muscle preparation, 5-, 10-, 20-, and 30-second pulses were applied at 30 to 40 W via a standard 4-mm tip electrode with 10-g contact pressure. Forty-one undisturbed pulses were delivered while recording intramural temperatures at 2-, 4-, and 7-mm depth. Maximal “thermal latency” was observed with the shortest pulse duration and at greatest depth. With 5-second applications, tissue temperature at 7-mm depth peaked 11.6 seconds after termination of radiofrequency delivery and stayed above end-of-pulse value as long as 34.5 seconds after the pulse. The additional rise in tissue temperature was 2.9°C. If only recordings within the lesion border zone were considered, the duration of latency was maximal with 10-second pulses: an additional gain in tissue temperature of 3.4°C was observed 6.4 seconds after the pulse while tissue temperature stayed above end-of-pulse value during 18.3 seconds.

Conclusions
With relatively short applications, tissue temperature continues to rise after termination of radiofrequency delivery. This “thermal latency” may result in lesion growth after the pulse and may so explain the incidentally observed progression of conduction block after short pulses in the vicinity of the atrioventricular node. It also may explain the apparent discrepancy between lesion growth rate and intramural temperature rise studies.
Expression of Inducible Nitric Oxide Synthase in Human Heart Failure
Authors: Haywood Guy A. , Tsao Philip S. , von der Leyen Heiko E. , Mann Michael J. , Keeling Philip J. , Trindade Pedro T. , Lewis Neil P. , Byrne Christopher D. , Rickenbacher Peter R. , Bishopric Nanette H. , Cooke John P. , McKenna William J. , Fowler Michael B.
Published: June 2012

Background
There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiological importance in heart failure. A number of studies have shown altered nitric oxide production by the endothelial constitutive isoform of nitric oxide synthase (NOS), but there is very little information on the role of the inducible isoform.

Methods and Results
We analyzed inducible NOS (iNOS) expression in ventricular myocardium taken from 11 control subjects (who had died suddenly from noncardiac causes), from 10 donor hearts before implantation, and from 51 patients with heart failure (24 with dilated cardiomyopathy [DCM], 17 with ischemic heart disease [IHD], and 10 with valvular heart disease [VHD]). Reverse transcription–polymerase chain reaction was used to confirm the presence of intact mRNA and to detect expression of iNOS and atrial natriuretic peptide (ANP). ANP was used as a molecular phenotypic marker of ventricular failure. iNOS was expressed in 36 of 51 biopsies (71%) from patients with heart failure and in none of the control patients (
P
<.0001). iNOS expression could also be detected in 50% of the donor hearts. All samples that expressed iNOS also expressed ANP. iNOS gene expression occurred in 67% of patients with DCM, 59% of patients with IHD, and 100% of patients with VHD. To determine whether iNOS protein was expressed in failing ventricles, immunohistochemistry was performed on three donor hearts and nine failing hearts with iNOS mRNA expression. Staining for iNOS was almost undetectable in the donor myocardium and in control sections, but all failing hearts showed diffuse cytoplasmic staining in cardiac myocytes. Expression of iNOS could be observed in all four chambers. Western blot analysis with the same primary antibody showed a specific positive band for iNOS protein in the heart failure specimens; minimal iNOS protein expression was seen in donor heart samples.

Conclusions
iNOS expression occurs in failing human cardiac myocytes and may be involved in the pathophysiology of DCM, IHD, and VHD.
Relation of Mean Right Atrial Pressure to Echocardiographic and Doppler Parameters of Right Atrial and Right Ventricular Function
Authors: Nagueh Sherif F. , Kopelen Helen A. , Zoghbi William A.
Published: June 2012

Background
A paucity of data exists as to the relation of mean right atrial pressure (RAP) to Doppler parameters of right atrial and ventricular filling. Furthermore, whether echocardiographic parameters of right atrial and right ventricular function and inferior vena cava improve the relation of Doppler filling dynamics with RAP has not been explored.

Methods and Results
Doppler and echocardiographic studies were performed simultaneously with measurements of mean RAP in consecutive patients who either had a central venous catheter in the Intensive Care Unit or underwent catheterization of the right side of the heart. The initial population consisted of 35 patients with a mean age (±SD) of 60±15 years; 34% were on mechanical ventilation. Mean RAP averaged 9±5.7 mm Hg (range, 2 to 28 mm Hg). Among tricuspid inflow parameters, the strongest relation with RAP was observed with the ratio of early to late velocity (
r
=.66). For hepatic venous flow, systolic filling wave indexes had the best relation with atrial pressure, the highest being for systolic filling fraction (
r
=−.86). Weaker relations were noted with the use of right atrial volumes, right ventricular function, and inferior vena caval diameters. The addition of any of these variables did not improve the relation of systolic filling fraction with RAP. The regression equation (RAP=21.6−24 systolic filling fraction) was tested prospectively in the estimation of atrial pressure in 50 patients. The correlation coefficient was .89 in the prospective group and .88 in the total group of 85 patients. The mean difference between predicted and actual pressures in the whole population was −0.2±2.6 mm Hg. The sensitivity and specificity for mean RAP>8 mm Hg were 86% and 92%, respectively.

Conclusions
Among echocardiographic and Doppler parameters of right atrial and right ventricular function, hepatic venous flow dynamics relate best to mean atrial pressure and can be used clinically to estimate mean RAP.
Increased Shear Stress Overcomes the Antithrombotic Platelet Inhibitory Effect of Aspirin in Stenosed Dog Coronary Arteries
Authors: Maalej Nabil , Folts John D.
Published: June 2012

Background
Shear stress is one of the known platelet activating mechanisms that leads to thrombosis. Increased shear stress has also been postulated to reverse the antithrombotic effect of some drugs such as aspirin (ASA).

Methods and Results
Experiments were conducted in five dogs to determine the minimal shear stress levels that produce acute platelet thrombus formation in mechanically stenosed arteries and the increase in shear required to reverse the antithrombotic effect of ASA. After intimal and medial damage, stenosis was produced in the circumflex coronary artery. We used the finite-difference numerical solution of the Navier-Stokes equation to determine the wall shear stresses in the area of stenosis. At 70±6% coronary diameter reduction, cyclic flow reductions (CFRs) caused by acute platelet thrombus formation were observed in the stenosed lumen. At this level of stenosis, the shear stress was 144±15 Pa. ASA given at a dose of 5 mg/kg IV inhibited in vivo acute platelet-mediated thrombus formation and abolished CFRs in all dogs. However, increasing the stenosis level to 80±5% caused the CFRs to return. The shear stress increased with the increased level of stenosis to 226±22 Pa. Thus, an average 10% increase in diameter narrowing caused a 56±20% increase in shear stress (
P
<.005) and renewed platelet activation and thrombus formation despite ASA pretreatment.

Conclusions
Individuals who take ASA daily to prevent coronary artery thrombus formation may not be well protected when a change in hemodynamics, such as an acute hypertensive episode, or an increase in stenosis severity due to a ruptured atherosclerotic plaque causes an increase in shear stress.
Endogenous Endothelin-1 Participates in the Maintenance of Cardiac Function in Rats With Congestive Heart Failure
Authors: Sakai Satoshi , Miyauchi Takashi , Sakurai Takeshi , Kasuya Yoshitoshi , Ihara Masaki , Yamaguchi Iwao , Goto Katsutoshi , Sugishita Yasuro
Published: June 2012

Background
Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin
A
(ET
A
) receptor antagonist, on both heart rate and myocardial contractility in rats with CHF.

Methods and Results
We used the left coronary artery–ligated rat model of CHF (CHF rats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHF rats than in the sham-operated rats (
P
<.01). In the left ventricle, the expression of prepro–ET-1 mRNA was markedly higher in the CHF rats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHF rats than in the sham-operated rats (500±41 versus 102±10 pg/g tissue,
P
<.01). Myocardial ET receptors were significantly higher in the CHF rats than in the sham-operated rats (243±20 versus 155±17 fmol/mg protein,
P
<.05). In the CHF rats, intravenous BQ-123 infusion (0.1 mg·kg
−1
·min
−1
for 120 minutes) significantly decreased both heart rate (
P
<.01) and LV+dP/dt
max
(
P
<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats.

Conclusions
In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHF rats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt
max
in the CHF rats but not in the sham-operated rats. Therefore, the ET receptor–mediated signal transduction system in the heart appears to be markedly stimulated in the CHF rats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.
Novel Biochemical Diagnostic Method for Aortic Dissection
Authors: Suzuki Toru , Katoh Hirohisa , Watanabe Masafumi , Kurabayashi Masahiko , Hiramori Katsuhiko , Hori Shingo , Nobuyoshi Masakiyo , Tanaka Hiromitsu , Kodama Kazuhisa , Sato Hikaru , Suzuki Shin , Tsuchio Yasuhiro , Yazaki Yoshio , Nagai Ryozo
Published: June 2012

Background
Aortic dissection is one of the most common aortic catastrophes. Although newer diagnostic methods as exemplified by image diagnostic techniques have greatly improved the diagnosis of aortic dissection, the diagnosis is still frequently missed today because the signs and symptoms of the disease are at times obscure. A reliable biochemical diagnostic method for aortic dissection would be beneficial.

Methods and Results
A novel biochemical diagnostic method for diagnosis of aortic dissection was developed that uses an immunoassay of monoclonal antibodies to smooth muscle myosin heavy chain. A prospective study was conducted to ascertain the usefulness of the method in the diagnosis of aortic dissection. Twenty-seven patients with aortic dissection admitted within the first 24 hours after onset were enrolled. Serial assay of serum smooth muscle myosin heavy chain showed significant elevations within the first 24 hours after onset of aortic dissection, with levels exceeding 10 ng/mL, with subsequent rapid reductions. The sensitivity of the assay within the first 12 hours was 90%, with a specificity of 97%. Analysis of 65 patients with acute myocardial infarction showed that the method could accurately differentiate myocardial infarction from aortic dissection.

Conclusions
The immunoassay of serum smooth muscle myosin heavy chain is a rapid and reliable biochemical method in the diagnosis of aortic dissection. The potential use of the method in clinical medicine is promising.
Levels of Soluble Cell Adhesion Molecules in Patients With Dyslipidemia
Authors: Hackman Anne , Abe Yasunori , Insull William , Pownall Henry , Smith Louis , Dunn Kay , Gotto Antonio M. , Ballantyne Christie M.
Published: June 2012

Background
Increased expression of cell adhesion molecules (CAMs) on the vascular endothelium has been postulated to play an important role in atherogenesis. Both in vitro and in vivo studies have suggested that dyslipidemia may increase expression of CAMs.

Methods and Results
To determine whether dyslipidemia is associated with increased expression of CAMs, we examined the levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble E-selectin (sE-selectin) in individuals with either hypercholesterolemia or hypertriglyceridemia and in control subjects matched for age and sex. Patients with hypertriglyceridemia had significantly higher levels of sVCAM-1 (739±69 ng/mL) compared with patients with hypercholesterolemia (552±63 ng/mL) and control subjects (480±56 ng/mL). Levels of sICAM-1 were significantly increased in both the hypercholesterolemic and hypertriglyceridemic groups (298±29 and 342±31 ng/mL, respectively) compared with the control group (198±14 ng/mL). Levels of sE-selectin were significantly increased in hypercholesterolemic patients (74±9 ng/mL) compared with control subjects (48±5 ng/mL). Ten hypercholesterolemic patients were treated aggressively with atorvastatin alone or a combination of colestipol and either atorvastatin or simvastatin for a mean of 42 weeks and had an average LDL cholesterol reduction of 51%. Comparison of soluble CAMs before and after treatment showed a significant reduction only in sE-selectin (77±11 versus 56±6 ng/mL,
P
≤.03) but not for sVCAM-1 or sICAM-1.

Conclusions
Although severe hyperlipidemia is associated with increased levels of soluble CAMs, aggressive lipid-lowering treatment had only limited effects on the levels. Increased levels of soluble CAMs in patients with hyperlipidemia may be a marker for atherosclerosis.
Seeding of Vascular Grafts With Genetically Modified Endothelial Cells
Authors: Dunn Peter F. , Newman Kurt D. , Jones Michael , Yamada Izumi , Shayani Vafa , Virmani Renu , Dichek David A.
Published: June 2012

Background
Seeding of small-diameter vascular grafts with endothelial cells (ECs) genetically engineered to secrete fibrinolytic or antithrombotic proteins offers the potential to improve graft patency rates.

Methods and Results
Sheep venous ECs were transduced with a retroviral vector encoding human tissue plasminogen activator (TPA). The ECs were seeded onto 4-mm-ID synthetic (Dacron) grafts. Retention of the seeded ECs was measured 2 hours after placement of the seeded grafts both in vitro in a nonpulsatile flow system and in vivo (in sheep) as femoral and carotid interposition grafts. On exposure to flow in vitro, ECs transduced with TPA were retained at a significantly lower rate (median, 67%) than either untransduced ECs (81%) or ECs transduced with a control retroviral vector producing β-galactosidase (β-Gal) (80%) (
P
<.05 for TPA versus either control). On implantation in vivo, ECs transduced with TPA were retained at a very low rate (median, 0%), significantly less than the retention of ECs transduced with the β-Gal vector (32%;
P
<.00001). Decreased in vivo retention of ECs transduced with TPA correlated modestly with increased in vitro cellular passage level (
r
2
=.48;
P
<.0001) but not with in vivo blood flow rate (
P
=.45). Addition of the protease inhibitor aprotinin to the cell culture and graft perfusion media resulted in a significant (
P
<.05) increase in in vitro retention of ECs transduced with TPA.

Conclusions
Increased TPA expression significantly decreases seeded EC adherence in vitro and in vivo. Gene therapy strategies for decreasing graft thrombosis may require expression of antithrombotic molecules that lack proteolytic activity.
Right Ventricular Diastolic Dysfunction in Heart Failure
Authors: Yu C.M. , Sanderson J.E. , Chan Skiva , Yeung Leata , Hung Y.T. , Woo K.S.
Published: June 2012

Background
Left ventricular (LV) diastolic dysfunction is common in heart failure and is an important predictor of prognosis and mortality. Less attention has been paid to right ventricular (RV) diastolic function. In this study, we compared RV diastolic function in a large cohort of patients with heart failure (HF) with two groups: patients with pulmonary hypertension and normal LV function (the PHT group) and normal subjects.

Methods and Results
Transtricuspid and pulmonary artery flow were assessed by two-dimensional Doppler echocardiography at maximum inspiration and expiration in 185 subjects: 114 symptomatic HF patients (ejection fraction <0.5), 31 PHT patients (pulmonary artery systolic pressure >40 mm Hg), and 40 normal subjects. A subset was matched for age and heart rate. The results showed a high prevalence of RV diastolic abnormalities: HF patients had lower tricuspid E-A ratios, lower peak E-wave velocity, and prolonged RV isovolumic relaxation time (all
P
<.0001). Tricuspid E-wave deceleration time was significantly shorter only in those who had an LV restrictive filling pattern. The PHT group had similar findings. Compared with a normal range, more than half of the patients had lower tricuspid E-A ratios (HF, 55%; PHT, 69%), and 61% of HF and 58% of PHT patients had a prolonged RV isovolumic relaxation time. In the PHT group, RV diastolic parameters (E-wave deceleration time, E-A ratio, and isovolumic relaxation time) correlated significantly with pulmonary artery systolic pressure (
P
<.05). In the HF group, however, only tricuspid E-wave deceleration time correlated significantly with pulmonary artery systolic pressure, and HF patients with normal pulmonary artery systolic pressures had significantly lower tricuspid E-A ratios and prolonged RV isovolumic relaxation times compared with normal subjects. A close correlation existed between individual RV and LV diastolic parameters, suggesting that LV diastolic dysfunction may directly affect RV function, but there was no relation between LV size or systolic function and RV diastolic dysfunction.

Conclusions
RV diastolic function is frequently abnormal in HF patients, and this is not related to elevated pulmonary artery systolic pressure alone, although high pulmonary artery pressure by itself also is associated with impaired RV diastolic function. Assessment of the role of right ventricular diastolic function in determining the symptoms and prognosis of heart failure is warranted.
Impaired Heart Rate Response to Graded Exercise
Authors: Lauer Michael S. , Okin Peter M. , Larson Martin G. , Evans Jane C. , Levy Daniel
Published: June 2012

Background
Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality. These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome. This investigation was designed to look at the prognostic implications of exercise heart rate response in a population-based sample.

Methods and Results
In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking β-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied. Heart rate response was assessed in three ways: (1) failure to achieve 85% of the age-predicted maximum heart rate, which has been the traditional definition of chronotropic incompetence; (2) the actual increase in heart rate from rest to peak exercise; and (3) the ratio of heart rate to metabolic reserve used by stage 2 of exercise (“chronotropic response index”). Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up. Failure to achieve target heart rate occurred in 327 (21%) subjects. During follow-up there were 55 deaths (14 caused by coronary heart disease) and 95 cases of incident coronary heart disease. Failure to achieve target heart rate, a smaller increase in heart rate with exercise, and the chronotropic response index were predictive of total mortality and incident coronary heart disease (
P
<.01). Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age, ST-segment response, physical activity, and traditional coronary disease risk factors (adjusted hazard ratio, 1.75; 95% confidence interval, 1.11 to 2.74;
P
=.02). After adjusting for the same factors, the increase in exercise heart rate remained inversely predictive of total mortality (
P
=.04) and coronary heart disease incidence (
P
=.0003). The chronotropic response index also was predictive of total mortality (
P
=.05) and incident coronary heart disease (
P
=.001) after adjusting for age and other risk factors.

Conclusions
An attenuated heart rate response to exercise, a manifestation of chronotropic incompetence, is predictive of increased mortality and coronary heart disease incidence.
Fundamental Relations Between Short-term RR Interval and Arterial Pressure Oscillations in Humans
Authors: Taylor J. Andrew , Eckberg Dwain L.
Published: June 2012

Background
One of the principal explanations for respiratory sinus arrhythmia is that it reflects arterial baroreflex buffering of respiration-induced arterial pressure fluctuations. If this explanation is correct, then elimination of RR interval fluctuations should increase respiratory arterial pressure fluctuations.

Methods and Results
We measured RR interval and arterial pressure fluctuations during normal sinus rhythm and fixed-rate atrial pacing at 17.2±1.8 (SEM) beats per minute greater than the sinus rate in 16 healthy men and 4 healthy women, 20 to 34 years of age. Measurements were made during controlled-frequency breathing (15 breaths per minute or 0.25 Hz) with subjects in the supine and 40° head-up tilt positions. We characterized RR interval and arterial pressure variabilities in low-frequency (0.05 to 0.15 Hz) and respiratory-frequency (0.20 to 0.30 Hz) ranges with fast Fourier transform power spectra and used cross-spectral analysis to determine the phase relation between the two signals. As expected, cardiac pacing eliminated beat-to-beat RR interval variability. Against expectations, however, cardiac pacing in the supine position significantly reduced arterial pressure oscillations in the respiratory frequency (systolic, 6.8±1.8 to 2.9±0.6 mm Hg
2
/Hz,
P
=.017). In contrast, cardiac pacing in the 40° tilt position increased arterial pressure variability (systolic, 8.0±1.8 to 10.8±2.6,
P
=.027). Cross-spectral analysis showed that 40° tilt shifted the phase relation between systolic pressure and RR interval at the respiratory frequency from positive to negative (9±7° versus −17±11°,
P
=.04); that is, in the supine position, RR interval changes appeared to lead arterial pressure changes, and in the upright position, RR interval changes appeared to follow arterial pressure changes.

Conclusions
These results demonstrate that respiratory sinus arrhythmia can actually contribute to respiratory arterial pressure fluctuations. Therefore, respiratory sinus arrhythmia does not represent simple baroreflex buffering of arterial pressure.
Heart Valve Involvement (Libman-Sacks Endocarditis) in the Antiphospholipid Syndrome
Authors: Hojnik Maja , George Jacob , Ziporen Lea , Shoenfeld Yehuda
Published: June 2012

Abstract
The antiphospholipid syndrome (APS) is defined by the presence of anti-phospholipid antibodies (aPLs) and venous or arterial thrombosis, recurrent pregnancy loss, or thrombocytopenia. The syndrome can be either primary or secondary to an underlying condition, most commonly systemic lupus erythematosus (SLE). Echocardiographic studies have disclosed heart valve abnormalities in about a third of patients with primary APS. SLE patients with aPLs have a higher prevalence of valvular involvement than those without these antibodies. Valvular lesions associated with aPLs occur as valve masses (nonbacterial vegetations) or thickening. These two morphological alterations can be combined and are thought to reflect the same pathological process. Both can be associated with valve dysfunction, although such association is much more common with the latter alteration. The predominant functional abnormality is regurgitation; stenosis is rare. The mitral valve is mainly affected, followed by the aortic valve. Valvular involvement usually does not cause clinical valvular heart disease. The presence of aPLs seems to further increase the risk for thromboembolic complications, mainly cerebrovascular, posed by valve lesions. Superadded bacterial endocarditis is rare but may be difficult to distinguish from pseudoinfective endocarditis. The current therapeutic guidelines are those for APS in general. Secondary antithrombotic prevention with long-term, high-intensity oral anticoagulation is advised. The efficacy of aspirin, either alone or in combination, is yet to be assessed. Corticosteroids are not beneficial and may even facilitate valve damage. Immunosuppressive agents should only be used for the treatment of an underlying condition. Current data suggest a role for aPLs in the pathogenesis of valvular lesions. aPLs may promote the formation of valve thrombi. These antibodies may also act by another mechanism, as indicated by the finding of subendothelial deposits of immunoglobulins, including anti-cardiolipin antibodies, and of colocalized complement components in deformed valves from patients with APS.
Cardiac Sympathetic Nerve Function in Congestive Heart Failure
Authors: Eisenhofer Graeme , Friberg Peter , Rundqvist Bengt , Quyyumi Arshed A. , Lambert Gavin , Kaye David M. , Kopin Irwin J. , Goldstein David S. , Esler Murray D.
Published: June 2012

Background
Increased availability of norepinephrine (NE) for activation of cardiac adrenoceptors (increased cardiac adrenergic drive) and depletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a comprehensive neurochemical approach to examine the mechanisms responsible for these abnormalities.

Methods and Results
Subjects with and without congestive heart failure received intravenous infusions of [
3
H]NE. Cardiac spillover, reuptake, vesicular-axoplasmic exchange, and tissue stores of NE were assessed from arterial and coronary venous plasma concentrations of endogenous and [
3
H]-labeled NE and dihydroxyphenylglycol. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the efficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Cardiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillover of dopa and NE turnover were increased similarly in congestive heart failure.

Conclusions
Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive in congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.
Coronary Vasodilation Induced by Angiotensin-Converting Enzyme Inhibition In Vivo
Authors: Sudhir Krishnankutty , Chou Tony M. , Hutchison Stuart J. , Chatterjee Kanu
Published: June 2012

Background
We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation.

Methods and Results
In seven anesthetized dogs, a Doppler guidewire was placed in the circumflex coronary artery to measure coronary flow velocity, and an ultrasound imaging catheter was introduced over the Doppler wire to measure coronary cross-sectional area. Drugs were infused directly into the left main coronary artery to minimize systemic effects. Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow. Pretreatment with
N
ω
-nitro-
l
-arginine methyl ester (100 μmol/L intracoronary) to block nitric oxide synthase attenuated ramiprilat-induced increase in epicardial coronary cross-sectional area (
P
<.05) but not in coronary flow velocity or coronary blood flow. In contrast, pretreatment with the selective bradykinin antagonist HOE 140 (10 μmol/L) attenuated ramiprilat-induced increase in flow velocity (
P
<.025) and coronary blood flow (
P
<.05) but not epicardial coronary cross-sectional area. Pretreatment with indomethacin (5 mg/kg body wt IV) did not alter ramiprilat-induced increase in epicardial cross-sectional area, nor did it significantly influence coronary blood flow.

Conclusions
Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.
Vitamin E Deficiency in Variant Angina
Authors: Miwa Kunihisa , Miyagi Yuko , Igawa Akihiko , Nakagawa Keiko , Inoue Hiroshi
Published: June 2012

Background
Oxidative modification of LDL has been suggested to increase coronary vasoreactivity to agonists. A deficiency of vitamin E, a major antioxidant, may be related to the occurrence of coronary artery spasm.

Methods and Results
Vitamin E levels were determined with the use of high-performance liquid chromatography in normolipidemic subjects, including 29 patients with active variant angina (group 1), 13 patients with inactive stage of variant angina without anginal attacks during the past 6 months (group 2), 32 patients with a significant (>75%) organic coronary stenosis and stable effort angina (group 3), and 30 patients without coronary artery disease (group 4). Total lipid levels in blood were calculated as total cholesterol plus triglyceride levels. The plasma α-tocopherol levels as well as α-tocopherol/lipids were significantly lower in group 1 than in groups 2 through 4. Also, the plasma γ-tocopherol levels were significantly lower in group 1 than in groups 2 through 4. The vitamin E levels were not significantly different between group 1 patients with and those without a significant organic stenosis. In group 1, both α- and γ-tocopherol levels were significantly elevated after a ≥6-month angina-free period. The α-tocopherol levels in the LDL fraction were significantly lower in group 1 than in group 4. Plasma α-tocopherol levels were significantly correlated with those in the LDL fractions. In 6 patients of group 1 still having anginal attacks while receiving calcium channel blockers, the addition of vitamin E acetate (300 mg/d) significantly elevated plasma α-tocopherol levels and inhibited the occurrence of angina.

Conclusions
Plasma vitamin E levels were significantly lower in patients with active variant angina than in subjects without coronary spasm, suggesting an association between vitamin E deficiency and coronary artery spasm.
Arterial Remodeling After Coronary Angioplasty
Authors: Mintz Gary S. , Popma Jeffrey J. , Pichard Augusto D. , Kent Kenneth M. , Satler Lowell F. , Chiu Wong S. , Hong Mun K. , Kovach Julie A. , Leon Martin B.
Published: June 2012

Background
Restenosis occurs after 30% to 50% of transcatheter coronary procedures; however, the natural history and pathophysiology of restenosis are still incompletely understood.

Methods and Results
Serial (postintervention and follow-up) intravascular ultrasound imaging was used to study 212 native coronary lesions in 209 patients after percutaneous transluminal coronary angioplasty, directional coronary atherectomy, rotational atherectomy, or excimer laser angioplasty. The external elastic membrane (EEM) and lumen cross-sectional areas (CSA) were measured; plaque plus media (P+M) CSA was calculated as EEM minus lumen CSA. The anatomic slice selected for serial analysis had an axial location within the target lesion at the smallest follow-up lumen CSA. At follow-up, 73% of the decrease in lumen (from 6.6±2.5 to 4.0±3.7 mm
2
,
P
<.0001) was due to a decrease in EEM (from 20.1±6.4 to 18.2±6.4 mm
2
,
P
<.0001); 27% was due to an increase in P+M (from 13.5±5.5 to 14.2±5.4 mm
2
,
P
<.0001). ΔLumen CSA correlated more strongly with ΔEEM CSA (
r
=.751,
P
<.0001) than with ΔP+M CSA (
r
=.284,
P
<.0001). ΔEEM was bidirectional; 47 lesions (22%) showed an increase in EEM. Despite a greater increase in P+M (1.5±2.5 versus 0.5±2.0 mm
2
,
P
=.0009), lesions exhibiting an increase in EEM had (1) no change in lumen (−0.1±3.3 versus 3.6±2.3 mm
2
,
P
<.0001), (2) a reduced restenosis rate (26% versus 62%,
P
<.0001), and (3) a 49% frequency of late lumen gain (versus 1%,
P
<.0001) compared with lesions with no increase in EEM.

Conclusions
Restenosis appears to be determined primarily by the direction and magnitude of vessel wall remodeling (ΔEEM). An increase in EEM is adaptive, whereas a decrease in EEM contributes to restenosis.