bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Exercise Capacity Using Submaximal Exercise at a Constant Work Rate in Patients With Cardiovascular Disease
Authors: Koike Akira , Yajima Takashi , Adachi Hiromasa , Shimizu Noritaka , Kano Hiroshi , Sugimoto Keiichi , Niwa Akihiro , Marumo Fumiaki , Hiroe Michiaki
Published: June 2012

Background
Symptom-limited incremental exercise tests are used to estimate the severity of cardiovascular disease and the patient’s daily activity. However, there is a need for objective parameters for submaximal exercise. To test the hypothesis that a decrease in maximal exercise capacity can be estimated by oxygen uptake (V̇
o
2
) kinetics, we measured the time constant of V̇
o
2
both during the onset of constant work rate exercise at 50 W and during recovery from this exercise and compared it with data obtained during maximal exercise in patients with cardiovascular disease and in normal subjects.

Methods and Results
A total of 34 patients with cardiovascular disease and 14 normal subjects performed 6 minutes of 50-W constant work rate exercise and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. V̇
o
2
was calculated from respiratory gas analysis on a breath-by-breath basis. The time constant of V̇
o
2
during the onset of 50-W exercise was 61.4±15.2 seconds in patients with cardiovascular disease, significantly longer (the kinetics of V̇
o
2
were slower) than that in normal subjects (48.8±10.4 seconds,
P
=.008). The time constant of V̇
o
2
during the onset of exercise was significantly negatively correlated with peak V̇
o
2
(
r
=−.67) and maximal work rate (
r
=−.66). The time constant during recovery, which did not differ significantly from that of exercise, was also prolonged in patients with cardiovascular disease; it showed a negative correlation with peak V̇
o
2
(
r
=−.63) and maximum work rate (
r
=−.54).

Conclusions
The time constant of V̇
o
2
during and after recovery from 50 W of constant work rate exercise, which does not require the subject’s maximal effort, is a useful and objective measure of exercise capacity in patients with mild to moderate cardiovascular disease.
Effect of Continuous Positive Airway Pressure on Intrathoracic and Left Ventricular Transmural Pressures in Patients With Congestive Heart Failure
Authors: Naughton Matthew T. , Rahman M. Atiar , Hara Kazuhiro , Floras John S. , Bradley T. Douglas
Published: June 2012

Background
Continuous positive airway pressure (CPAP) can improve cardiac function in patients with congestive heart failure (CHF). We hypothesized that this effect might be related to CPAP-induced increases in intrathoracic pressure, which would reduce left ventricular transmural pressure (LVP
tm
) during systole, thereby decreasing left ventricular afterload.

Methods and Results
The effect of graduated CPAP from 0 to 10 cm H
2
O on the above variables was examined over a 75-minute period and compared with a 75-minute time control period without CPAP in two groups of subjects: 15 patients with CHF and 9 healthy subjects. Intrathoracic pressure was estimated from esophageal pressure (P
es
), and systolic LVP
tm
, a determinant of left ventricular afterload, was assessed by subtracting P
es
during systole from systolic blood pressure. Cardiac index (CI) was assessed by Doppler echocardiography. At baseline, inspiratory P
es
amplitude, which reflects inspiratory muscle force generation, was greater in the patients with CHF than in the healthy group (9.9±0.8 versus 5.5±0.4 mm Hg,
P
<.001). In addition, systolic P
es
, which represents the relative contribution of intrathoracic pressure to LVP
tm
, was more negative in the patients with CHF than in the healthy group (−4.1±0.3 versus −2.2±0.1 mm Hg,
P
<.001). While on CPAP of 10 cm H
2
O, inspiratory P
es
amplitude decreased and systolic P
es
increased significantly in the group with CHF (from 11.1±1.1 to 7.5±1.1 mm Hg,
P
<.025 and from −4.7±0.6 to 0.6±0.6 mm Hg,
P
<.001, respectively), but CPAP had no effect on these variables in the healthy subjects. Compared with the equivalent time control period, P
es
amplitude×respiratory rate decreased significantly while on CPAP in both the group with CHF (from 188±22 to 112±17 mm Hg×breaths per minute,
P
<.005) and the healthy group (from 82±8 to 60±6 mm Hg×breaths per minute,
P
<.05). Compared with time control, systolic LVP
tm
decreased significantly while on CPAP, from 116.0±5.3 to 110.3±4.5 mm Hg (
P
<.025) in the group with CHF, but did not change in the healthy group. Moreover, systolic LVP
tm
×heart rate decreased significantly in the group with CHF (from 80.55±5.27 to 71.83±4.73 mm Hg×beats per minute/100,
P
<.005) but not in the healthy group. CI decreased significantly while on CPAP in the healthy group (
P
<.025) but did not change in the group with CHF.

Conclusions
In patients with CHF, the inspiratory muscles generate greater force per breath and systolic P
es
contributes more to LVP
tm
than in healthy subjects. By increasing intrathoracic pressure in patients with CHF, CPAP unloaded inspiratory muscles and reduced left ventricular afterload without compromising CI.
Long-term Luminal Renarrowing After Successful Elective Coronary Angioplasty of Total Occlusions
Authors: Violaris Andonis G. , Melkert Rein , Serruys Patrick W.
Published: June 2012

Background
The long-term angiographic outcome after successful dilatation of coronary occlusions remains unclear. The objective of this study was to examine long-term restenosis after successful balloon dilatation of coronary occlusions at a predetermined time interval with quantitative angiography and compare this with a control population of stenoses.

Methods and Results
The study population comprised 2950 patients (3583 lesions) prospectively enrolled in and successfully completing four major restenosis trials (86% quantitative angiographic follow-up). Cineangiographic films were processed and analyzed at a central core laboratory with the use of an automated interpolated edge detection technique. The study population comprised 266 occlusions (7%) defined as total when there was absent anterograde filling beyond the lesion (109 lesions) and functional (157 lesions) when faint, late anterograde opacification of the distal segment was seen in the absence of a discernible luminal continuity; 3317 lesions were defined as stenoses (93%). Restenosis was significantly higher after successful dilatation of occlusions than of stenoses. With the categorical (>50% diameter stenosis at follow-up) approach, the restenosis rate was 44.7% in occlusions compared with 34.0% in stenoses (
P
<.001; relative risk, 1.575; CI, 1.224 to 2.027). Similarly, the absolute loss (defined as the change in minimal lumen diameter between post coronary angioplasty and follow-up; in millimeters, mean±SD) (0.43±0.68) in occlusions was significantly higher than in stenoses (0.31±0.51,
P
<.001), as was the relative loss, defined as the change in minimal lumen diameter between postangioplasty and follow-up, adjusted for the vessel size (0.17±0.28 versus 0.12±0.20,
P
<.001). The higher restenosis rate in the occlusions group was due predominantly to an increased number of occlusions at follow-up angiography in this group (19.2% compared with 5.0% for stenoses,
P
<.001). Within the occlusions group, there were no significant differences in long-term outcome between total and functional occlusions (restenosis rate, 45.0% versus 44.6%; reocclusion rate, 23.9% versus 15.9%; absolute loss, 0.53±0.69 versus 0.36±0.67; relative loss, 0.21±0.28 versus 0.15±0.28;
P
=NS).

Conclusions
These results indicate that successfully dilated coronary occlusions, both total and functional, have a higher rate of angiographic restenosis at 6 months than stenoses. This is due chiefly to a higher rate of occlusion at follow-up angiography in this group of lesions. Measures aimed at reducing restenosis after successful dilatation of coronary occlusion should be focused in this direction.
Electrophysiological Effects of Flecainide on Anisotropic Conduction and Reentry in Infarcted Canine Hearts
Authors: Coromilas James , Saltman Adam E. , Waldecker Bernd , Dillon Stephen M. , Wit Andrew L.
Published: June 2012

Background
The class IC antiarrhythmic drug flecainide has been shown to be ineffective for the treatment of ventricular arrhythmias in some patients who have had a prior myocardial infarction and sometimes even provoke arrhythmias (proarrhythmic effect). Since some ventricular tachycardias may be caused by anisotropic reentry, we determined the effects of flecainide on this mechanism for reentry in infarcted canine hearts in order to determine possible causes for its clinical effects.

Methods and Results
The effects of flecainide were determined on ventricular tachycardia induced by programmed electrical stimulation in dogs with healing myocardial infarction 4 days after coronary artery occlusion. Activation in the reentrant circuits causing tachycardia was mapped with a 196-channel computerized mapping system. We found that flecainide converted inducible unsustained ventricular tachycardia to inducible sustained ventricular tachycardia by modifying conduction in the reentrant circuit. In general, by slowing conduction, the reentrant wave front did not block after flecainide, leading to perpetuation of reentrant excitation. When sustained ventricular tachycardia could be induced before the drug, flecainide prolonged the coupling interval of premature impulses necessary to induce tachycardia by lengthening the line of block and slowing conduction around it. Flecainide also slowed the rate of the tachycardia but did not terminate it. The anisotropic reentrant circuits were modified so that the central common pathway of “figure-of-eight” circuits was narrowed and lengthened due to extension of the lines of block that bounded the pathways. Extension of the lines of block resulted from depression of conduction in the direction transverse to the long axis of the myocardial fiber bundles caused by flecainide. Flecainide also slowed conduction in the longitudinal direction in part of the circuits. The depressant effects of flecainide on both longitudinal and transverse anisotropic conduction were quantified by pacing from the center of the electrode array and it was found, contrary to predictions, that transverse conduction was depressed as much as longitudinal conduction.

Conclusions
Flecainide slows conduction in both the longitudinal and transverse direction relative to the orientation of the myocardial fibers. This enables sustained reentry to occur more easily. Flecainide does not cause conduction block in crucial regions of reentrant circuits (central common pathway) and therefore does not prevent reentrant tachycardia in healing infarcts.
Age and Hypertension Differently Affect Coronary Contractions to Endothelin-1, Serotonin, and Angiotensins
Authors: Tschudi M.R. , Lüscher T.F.
Published: June 2012

Background
Endothelium-derived substances and the renin-angiotensin system are important regulators of vascular tone. This study was designed to evaluate the effects of age and hypertension on vascular function of rat coronary arteries.

Methods and Results
Rings of the left anterior descending coronary artery were isolated from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 12 (younger) and 72 (older) weeks of age and suspended in myographs (37°C, 95% O
2
/5% CO
2
) for isometric tension recording. Systolic blood pressure was higher in SHR than in WKY rats (
P
<.05) but was unaffected by age in both strains. Active wall tension to KCl 100 mmol/L (mN/mm) was decreased in younger (0.28±0.03, n=9) and older SHR (0.49±0.06, n=13) compared with age-matched WKY rats (0.87±0.05, n=9 and 1.51±0.11, n=11, respectively,
P
<.05). In both strains, active wall tension to endothelin-1 and serotonin increased with age (n=6 to 10,
P
<.05) but was decreased in younger and older SHR compared with WKY rats (
P
<.05). Active wall tension induced by angiotensin I 10
−7
mol/L was increased in older SHR (0.19±0.04, n=7) compared with younger SHR (0.04±0.01, n=9) but was similar in younger and older WKY rats (0.10±0.02 versus 0.15±0.03, n=6 to 9) and younger SHR. In younger WKY rats and SHR, pretreatment of coronary arteries with benazeprilat 10
−5
mol/L (n=5 for each) almost completely abolished the contractions to angiotensin I 10
−7
mol/L. Active wall tension to angiotensin II 10
−7
mol/L was comparable in all four groups, but compared with the contraction to KCl 100 mmol/L, the response was already increased in younger SHR (29±3%, n=9) compared with the younger WKY rats (14±3%, n=9,
P
<.05), but it was unaffected by age in both strains. In vitro treatment of younger WKY rat and SHR coronary arteries with the nonpeptide angiotensin II (AT
1
) receptor antagonist valsartan 10
−5
mol/L (n=3 for each) fully suppressed contractions to angiotensin II 10
−7
mol/L. In contrast, endothelium-independent relaxations to the nitrovasodilator sodium nitroprusside, endothelium-dependent relaxations to acetylcholine, and endothelium-dependent contractions to
N
ω
-nitro-
l
-arginine methyl ester were comparable in all four groups of rats.

Conclusions
In summary, in rat coronary arteries, contractile responses to endothelin-1, serotonin, and KCl increase with age but are decreased by hypertension. In contrast, the
l
-arginine/nitric oxide pathway remains unaffected. The contractions to angiotensin I markedly increased with increasing duration of hypertension in the SHR only. Despite overall reduced contractile responses of SHR coronary arteries, contractions to angiotensin II were maintained. Hence, aging and hypertension affect contractile responses of rat coronary arteries to vasoconstrictor agonists differently.
Fundamental Limitations of [
18
F]2-Deoxy-2-Fluoro-
d
-Glucose for Assessing Myocardial Glucose Uptake
Authors: Hariharan Ramesh , Bray Molly , Ganim Ricky , Doenst Torsten , Goodwin Gary W. , Taegtmeyer Heinrich
Published: June 2012

Background
The glucose tracer analog [
18
F]2-deoxy-2-fluoro-
d
-glucose (FDG) is widely used for assessing regional myocardial glucose metabolism in vivo. The reproducibility of this method has recently been questioned because of a discordant affinity of hexokinase for its substrates glucose and 2-deoxyglucose. We therefore compared rates of glucose utilization simultaneously with tissue time-activity curves of FDG uptake before and after changes in the physiological environment of the heart.

Methods and Results
Isolated working rat hearts were perfused for 60 minutes with recirculating Krebs buffer containing glucose (10 mmol/L), FDG (1 μCi/mL), [2-
3
H]glucose (0.05 μCi/mL), and [U-
14
C]2-deoxyglucose (2-DG; 0.025 μCi/mL). Myocardial glucose uptake was measured by tracer ([2-
3
H]glucose) and tracer analog methods (FDG and 2-DG) before and after the addition of either insulin (1 mU/mL), epinephrine (1 μmol/L), lactate (40 mmol/L), or
d,l
-β-hydroxybutyrate (40 mmol/L) at 30 minutes of perfusion and after acute changes in cardiac workload. Under steady-state conditions, myocardial rates of glucose utilization as measured by tritiated water (
3
H
2
O) production from metabolism of [2-
3
H]glucose, FDG uptake, and 2-DG retention were linearly related. The addition of competing substrates decreased glucose utilization immediately. The addition of insulin increased the rate of glucose utilization as measured by the glucose tracer but not as measured by the tracer analogs. The ratio of
3
H
2
O release/myocardial FDG uptake increased by 111% after the addition of insulin, by 428% after the addition of lactate, and by 232% after the addition of β-hydroxybutyrate. Epinephrine increased rates of glucose utilization and contractile performance, whereas there was no increase in glucose uptake with a comparable increase in workload alone. There was no change in the relation between the glucose tracer and the tracer analog either with epinephrine or with acute changes in workload.

Conclusions
The uptake and retention of FDG in heart muscle is linearly related to glucose utilization only under steady-state conditions. Addition of insulin or of competing substrates changes the relation between uptake of the glucose tracer and FDG. These observations preclude the determination of absolute rates of myocardial glucose uptake by the tracer analog method under non–steady-state conditions.
Experimental Ablation of Outflow Tract Muscle With a Thermal Balloon Catheter
Authors: Neya Kazuo , Lee Raymond , Guerrero J. Luis , Lang Peter , Vlahakes Gus J.
Published: June 2012

Background
Pulmonary balloon valvuloplasty has been performed in selected patients with tetralogy of Fallot as an alternative to surgical palliation; this technique is limited, however, by the fact that the balloon has little effect on the dynamic, muscular contribution to outflow tract obstruction. In an experimental model, we used a new thermal balloon catheter to ablate right ventricular outflow tract muscle. We evaluated the acute efficacy and muscle ablation parameters of this technology and its effects after myocardial healing.

Methods and Results
A prototype electrolyte-filled balloon catheter, heated by radiofrequency energy, was constructed. Studies were conducted to determine the optimum electrolyte solution needed to minimize balloon heating time with an unmodified, commercially available radiofrequency generator. In vivo ablations of right ventricular outflow tract muscle with the thermal balloon were performed in lambs that were divided into three groups (n=5 each) according to the duration of thermal energy delivery (20, 40, and 60 seconds, respectively). Ablated lesion volume increased (460±63 to 1156±256 mm
3
) as the energy delivery time increased (20 to 60 seconds) and was correlated with delivered energy, temperature integral, and maximum epicardial surface temperature (
r
=.85, .82, and .72, respectively). All five lesions in the 60-second group showed an acute decrease of the wall thickness. Additional in vivo ablations were performed in 6 animals in which survival studies showed muscle thinning, healing by fibrosis, and no evidence of aneurysm formation.

Conclusions
Thermal energy can be used with a balloon catheter delivery system to ablate myocardium. This study suggests that this energy delivery technology might be useful for relief of muscular outflow tract obstruction and that further studies are warranted.
Role of Endothelin-1 in Beagles With Dehydromonocrotaline-Induced Pulmonary Hypertension
Authors: Okada Morihito , Yamashita Chojiro , Okada Masayoshi , Okada Kenji
Published: June 2012

Background
Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)-induced PH.

Methods and Results
Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6±2.3 to 35.9±7.1 mm Hg and from 1.24±0.25 to 3.25±0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by
FR139317
(an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles,
FR139317
infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles.

Conclusions
These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors.
Effects of Load Manipulations, Heart Rate, and Contractility on Left Ventricular Apical Rotation
Authors: Kroeker Carol A. Gibbons , Tyberg John V. , Beyar Rafael
Published: June 2012

Background
Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured.

Methods and Results
Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61±0.06°/percent change; intercept, −60.1±6.2°; n=10) that differed from the end-systolic (ES) relation (slope, 1.36±0.27°/percent change; intercept, −132.5±24.9°;
P
<.005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation–volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period.

Conclusions
The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation.
Provocation of Hypotension During Head-Up Tilt Testing in Subjects With No History of Syncope or Presyncope
Authors: Natale Andrea , Akhtar Masood , Jazayeri Mohammad , Dhala Anwer , Blanck Zalmen , Deshpande Sanjay , Krebs Anita , Sra Jasbir S.
Published: June 2012

Background
Head-up tilt test is increasingly being used to evaluate patients with syncope. This study was designed to evaluate the specificity of head-up tilt testing using different tilt angles and isoproterenol infusion doses in normal volunteers with no prior history of syncope or presyncope.

Methods and Results
One hundred fifty volunteers were randomized to two groups of 75 each. In group 1, subjects were further randomized to have head-up tilt testing at a 60, 70, or 80 degree angle at baseline followed by repeat tilt testing during a low-dose isoproterenol infusion that increased the heart rate by an average of 20%. In group 2, after having a baseline head-up tilt test at a 70 degree angle for a maximum of 20 minutes, subjects were randomized to have a repeat tilt table testing at a 70 degree angle during a low-dose, 3 μg/min, or 5 μg/min isoproterenol infusion. In group 1, syncope or presyncope along with hypotension developed in 2 subjects during the baseline test at 60 and 70 degrees of tilt and in 5 subjects during tilting at 80 degrees. The addition of low-dose isoproterenol reduced the specificity minimally from 92% to 88% at both 60 and 70 degrees of tilt but substantially to 60% at an 80 degree angle. However, 6 of the 10 subjects with a positive test at an 80 degree angle had an abnormal response after 10 minutes of tilt testing. In group 2, using various isoproterenol doses with tilt table testing at a 70 degree angle, low-dose (mean infusion dose, 1.5±0.45 μg/min), 3 μg/min, and 5 μg/min isoproterenol infusions elicited an abnormal response in 1 (4%), 5 (20%), and 14 (56%) of the subjects, respectively. Using multiple logistic regression analysis, head-up tilt testing at an 80 degree angle (
P
=.01) or during 3 μg/min (
P
=.02) and 5 μg/min isoproterenol infusion rates (
P
<.001) was the most significant predictor of an abnormal response.

Conclusions
Head-up tilt testing at a 60 or 70 degree angle with or without low-dose isoproterenol infusion provides an adequate specificity. Caution is needed, however, in interpreting the results if the head-up tilt test at 80 degrees is extended beyond 10 minutes or if high doses of isoproterenol are used.
Atrial Electrogram Characteristics in Patients With and Without Atrioventricular Nodal Reentrant Tachycardia
Authors: Niebauer Mark J. , Daoud Emile , Williamson Brian , Man K. Ching , Strickberger Adam , Hummel John , Morady Fred
Published: June 2012

Background
Multicomponent atrial electrograms and “slow pathway potentials” are helpful in identifying target sites for radiofrequency catheter ablation of the slow pathway in patients with atrioventricular (AV) nodal reentrant tachycardia. The purpose of this study was to compare the atrial electrograms recorded at various locations in the right atrium in patients with and without AV nodal reentrant tachycardia to assess the specificity of multicomponent atrial electrograms and possible slow pathway potentials both for the posteroseptal right atrium and for patients with AV nodal reentrant tachycardia.

Methods and Results
In 25 patients with AV nodal reentrant tachycardia and 23 control patients without AV nodal reentrant tachycardia or dual AV nodal physiology, atrial electrograms with an AV ratio of ≤1:2 were recorded at the posteroseptal right atrium near the coronary sinus ostium and in the right atrium near the posterior, lateral, and anterior aspects of the tricuspid annulus. Attempts were made to identify broad, multicomponent, and double atrial electrograms. There were no significant differences between the patients with and without AV nodal reentrant tachycardia in the mean number of deflections in the atrial electrograms or in the mean duration of the atrial electrograms recorded at any of the atrial sites. In all patients, the number of atrial electrogram deflections and the atrial electrogram duration were significantly greater at the posteroseptal position than at the other three atrial sites. The prevalence of potentials with the appearance of slow pathway potentials in the posterior septum was similar in patients with and without AV nodal reentrant tachycardia (68% and 70%, respectively). The prevalence of these potentials was 6% to 25% at the other three atrial sites (
P
<.005 compared with the posterior septum).

Conclusions
The atrial electrogram characteristics that have been found to be useful in identifying effective posteroseptal slow pathway ablation sites in patients with AV nodal reentrant tachycardia are equally prevalent in patients without AV nodal reentrant tachycardia or dual AV nodal physiology. Atrial electrograms in the posteroseptal area are broader and contain more deflections than at other areas in the right atrium, possibly because of conduction properties of the posterior transitional zone that are independent of the presence of AV nodal reentrant tachycardia.
Stroke After Thrombolysis
Authors: Gore Joel M. , Granger Christopher B. , Simoons Maarten L. , Sloan Michael A. , Weaver W. Douglas , White Harvey D. , Barbash Gabriel I. , Van de Werf Frans , Aylward Philip E. , Topol Eric J. , Califf Robert M.
Published: June 2012

Background
Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial.

Methods and Results
Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Overall, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy (
P
=.007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy (
P
<.001). Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling, with no significant treatment-related differences. Stroke subtype affected prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions. Patients with moderate or severe residual deficits showed significantly decreased quality of life. Advanced age, lower weight, prior cerebrovascular disease or hypertension, systolic and diastolic blood pressures, randomization to tissue plasminogen activator, and an interaction between age and hypertension were significant predictors of intracranial hemorrhage.

Conclusions
Stroke remains a rare but catastrophic complication of thrombolysis. Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups, particularly the elderly and patients with prior cerebrovascular events.
Discrimination Between Myocardial and Skeletal Muscle Injury by Assessment of the Plasma Ratio of Myoglobin Over Fatty Acid–Binding Protein
Authors: Van Nieuwenhoven Frans A. , Kleine Appie H. , Wodzig K. Will H. , Hermens Wim T. , Kragten Hans A. , Maessen Jos G. , Punt Cees D. , Van Dieijen Marja P. , Van Der Vusse Ger J. , Glatz Jan F.C.
Published: June 2012

Background
Myoglobin and fatty acid–binding protein (FABP) each are useful as early biochemical markers of muscle injury. We studied whether the ratio of myoglobin over FABP in plasma can be used to distinguish myocardial from skeletal muscle injury.

Methods and Results
Myoglobin and FABP were assayed immunochemically in tissue samples of human heart and skeletal muscle and in serial plasma samples from 22 patients with acute myocardial infarction (AMI), from 9 patients undergoing aortic surgery (causing injury of skeletal muscles), and from 10 patients undergoing cardiac surgery. In human heart tissue, the myoglobin/FABP ratio was 4.5 and in skeletal muscles varied from 21 to 73. After AMI, the plasma concentrations of both proteins were elevated between ≈1 and 15 to 20 hours after the onset of symptoms. In this period, the myoglobin/FABP ratio was constant both in subgroups of patients receiving and those not receiving thrombolytics and amounted to 5.3±1.2 (SD). In serum from aortic surgery patients, both proteins were elevated between 6 and 24 hours after surgery; the myoglobin/FABP ratio was 45±22 (SD), which is significantly different from plasma values in AMI patients (
P
<.001). In patients with cardiac surgery, the ratio increased from 11.3±4.7 to 32.1±13.6 (SD) during 24 hours after surgery, indicating more rapid release of protein from injured myocardium than from skeletal muscles.

Conclusions
The ratio of the concentrations of myoglobin over FABP in plasma from patients with muscle injury reflects the ratio found in the affected tissue. Since this ratio is different between heart (4.5) and skeletal muscle (20 to 70), its assessment in plasma allows the discrimination between myocardial and skeletal muscle injury in humans.
N
-Acetylcysteine in Combination With Nitroglycerin and Streptokinase for the Treatment of Evolving Acute Myocardial Infarction
Authors: Arstall Margaret A. , Yang Jeifu , Stafford Irene , Betts W. Henry , Horowitz John D.
Published: June 2012

Background N
-acetylcysteine (NAC) has been shown to potentiate the effects of nitroglycerin (NTG) and to have antioxidant activity. This is the first study to assess the safety and effect of NAC in the treatment of evolving acute myocardial infarction (AMI).

Methods and Results
Patients with AMI received either 15 g NAC infused over 24 hours (n=20) or no NAC (n=7), combined with intravenous NTG and streptokinase. Peripheral venous plasma malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione concentrations, and rate of reperfusion (using continuous ST-segment analysis) were measured. Cardiac catheterization was performed between days 2 and 5. No significant adverse events occurred. Less oxidative stress occurred in patients treated with NAC than in patients not receiving NAC (GSH to GSSG ratio 44±25 versus 19±13 at 4 hours,
P
<.05). NAC concentration (mean 172±79 μmol/L at 4 hours) was correlated to GSH concentration (
P
=.006). MDA concentrations were lower (
P
=.001) over the first 8 hours of treatment with NAC. There was a trend toward more rapid reperfusion (median 58 minutes, 95% confidence interval [CI] 48 to 98 minutes versus median 95 minutes, 95% CI 59 to 106 minutes;
P
=.17) and better preservation of left ventricular function (cardiac index 3.4±0.8 versus 2.6±0.27 L · min · m
2
,
P
=.009) with NAC treatment.

Conclusions
NAC in combination with NTG and streptokinase appeared to be safe for the treatment of evolving AMI and was associated with significantly less oxidative stress, a trend toward more rapid reperfusion, and better preservation of left ventricular function.
Demonstrable Cardiac Reinnervation After Human Heart Transplantation by Carotid Baroreflex Modulation of RR Interval
Authors: Bernardi Luciano , Bianchini Beatrice , Spadacini Giammario , Leuzzi Stefano , Valle Felice , Marchesi Eugenia , Passino Claudio , Calciati Alessandro , Viganó Mario , Rinaldi Mauro , Martinelli Luigi , Finardi Giorgio , Sleight Peter
Published: June 2012

Background
After heart transplantation, respiration-synchronous fluctuations (0.18 to 0.35 Hz, high frequency [HF]) in RR interval may result from atrial stretch caused by changes in venous return, but slower fluctuations (0.03 to 0.15 Hz, low frequency [LF]) not due to respiration suggest reinnervation. In normal subjects, sinusoidal neck suction selectively stimulates carotid baroreceptors and causes reflex oscillations of RR interval.

Methods and Results
To evaluate the presence of reinnervation, we measured the power of RR-LF and RR-HF in 26 heart transplant recipients and 16 control subjects before and during sinusoidal neck suction at 0.1 Hz and 0.20 Hz (similar to but distinct from that of controlled respiration, 0.25 Hz) and before and during administration of atropine or β-blocker (esmolol hydrochloride) by spectral analysis. All transplant recipients showed small respiratory HF fluctuations. Nonrespiratory LF fluctuations were present in 13 of 26 transplant recipients and increased with months since transplantation (
r
=.53,
P
<.01). HF neck suction induced a 0.20-Hz component in all 16 control subjects and none of the 26 transplant subjects. LF neck suction increased RR-LF (from 0.73±0.20 to 1.30±0.26 ln ms
2
,
P
<.001), similar to but less than in control subjects (from 6.12±0.21 to 8.27±0.21 ln ms
2
,
P
<.001). Atropine reduced all fluctuations in control subjects and blocked the HF increase caused by 0.20-Hz neck suction but not the LF increase during 0.10-Hz stimulation. Neck suction–induced changes in LF fluctuations persisted after administration of atropine in transplant recipients but were attenuated by esmolol hydrochloride, suggesting sympathetic rather than vagal reinnervation.

Conclusions
The presence of baroreceptor-induced RR oscillations is evidence of functional, although incomplete, autonomic reinnervation.
Changes in Effective Regurgitant Orifice Throughout Systole in Patients With Mitral Valve Prolapse
Authors: Enriquez-Sarano Maurice , Sinak Lawrence J. , Tajik A. Jamil , Bailey Kent R. , Seward James B.
Published: June 2012

Background
In patients with mitral valve prolapse, spontaneous changes of the effective regurgitant orifice during systole are not well documented. Such changes can now be analyzed by use of the proximal isovelocity surface area method, but the changes raise concern about the reliability of this method for assessing overall severity of regurgitation in these patients.

Methods and Results
In a prospective study of 42 patients with mitral valve prolapse, the effective mitral regurgitant orifice was calculated at four phases of systole (early, mid, mid-late, and late) as the ratio of regurgitant flow to regurgitant velocity by use of the proximal isovelocity surface area method. Throughout systole, the effective regurgitant orifice increased significantly, from 32±27 mm
2
in early systole to 41±27 in midsystole, 55±30 in mid-late systole, and 107±66 mm
2
during late systole (
P
<.0001). Phasic regurgitant volume increased from early to mid-late systole but decreased in late systole. For quantitation of the overall effective regurgitant orifice, four approaches using the proximal isovelocity surface area were compared with simultaneously performed quantitative Doppler echocardiography (54±30 mm
2
) and quantitative two-dimensional echocardiography (51±29 mm
2
). All correlations were good (
r
>.95), but overestimation was considerable when the largest flow convergence was used (70±39 mm
2
; both
P
<.0001), significant when the simple mean of the four phases was used (59±36 mm
2
;
P
=.005 and
P
=.0007, respectively), mild when a weighted mean of the four phases was used (55±33 mm
2
;
P
=.41 and
P
=.01, respectively), and no overestimation was observed when the effective regurgitant orifice calculated at maximum regurgitant velocity was used (54±30 mm
2
;
P
=.29 and
P
=.17, respectively).

Conclusions
Phasic changes of mitral regurgitation are observed in patients with mitral valve prolapse. The effective regurgitant orifice increases throughout systole. Regurgitant volume also increases initially but tends to decrease in late systole. These changes can lead to overestimation of the overall degree of regurgitation, but properly timed measurements made by use of the proximal isovelocity surface area method allow an accurate estimation of the overall effective regurgitant orifice.
Circadian Variation in Coronary Tone in Patients With Stable Angina
Authors: El-Tamimi Hassan , Mansour Michael , Pepine Carl J. , Wargovich Thomas J. , Chen Henry
Published: June 2012

Background
Coronary endothelium plays a key role in the regulation of coronary tone, platelet adhesion, and aggregation, which are important factors in triggering acute cardiovascular events. However, its role in modulating the effects of circadian variations on coronary tone is not known.

Methods and Results
Responses of 72 nonstenotic coronary segments to acetylcholine and nitroglycerin were measured in 12 patients with chronic stable angina at 6
am
and 1
pm
. After baseline angiography, three infusions of acetylcholine (10
−6
, 10
−5
, and 10
−4
mol/L) were administered selectively into the left coronary artery, followed by nitroglycerin. Diameters (in millimeters) of proximal, middle, and distal segments were measured by quantitative techniques. Forty-seven segments showed a constrictor response to acetylcholine (group 1, dysfunctional endothelium), and 25 other segments showed a dilator response (group 2, normally functioning endothelium). In group 1, the constrictor response to acetylcholine was significantly greater in the morning than in the afternoon (23±3% and 10±1%, mean±SEM, respectively;
P
<.001), and the dilator response to nitroglycerin was also significantly greater in the morning than in the afternoon (19±2% and 11±2%;
P
<.01). In group 2, the dilator response to acetylcholine did not differ significantly between the morning and afternoon (22±3% and 17±2%, respectively;
P
=NS), and the dilator response to nitroglycerin was also similar at both times of the day (30±3% and 28±4%, respectively;
P
=NS).

Conclusions
Coronary segments with dysfunctional endothelium exhibit an early morning exaggeration in vasomotor activity, whereas segments with normally functioning endothelium do not show circadian variations. This suggests a potential protective role for the endothelium in modulating variations in coronary tone that may contribute to increased incidence of cardiovascular events in the early morning hours.
Patient Factors Associated With Strut Fracture in Björk-Shiley 60° Convexo-Concave Heart Valves
Authors: Walker Alexander M. , Funch Donnie P. , Sulsky Sandra I. , Dreyer Nancy A.
Published: June 2012

Background
Previously established predictors of outlet strut fracture in Björk-Shiley convexo-concave (CC) valves include larger valve size, larger opening angle (70° versus 60°), younger age at implant, and date of manufacture. We sought to identify patient characteristics that might be predictive of strut fracture and to refine the estimates associated with previously identified predictors.

Methods and Results
We conducted a case-control study of CC60° valves implanted in the United States and Canada and manufactured between January 1, 1979, and March 31, 1984. Cases included all valves with verified outlet strut fractures reported to the manufacturer from January 1979 through January 1992. Up to 10 controls were selected for each case. Control valves were matched according to implanting surgeon and were required to have been functioning at least as long as their matched case valves. Case and control medical records were reviewed for information on patient medical history before the valve implant. There were 96 case and 634 control valves for which clinical data were available. Patient age and valve size and implant position were confirmed as important determinants of fracture. There was a strong inverse gradient of risk with age. The risk of fracture was 42% lower for each 10-year increment of patient age at time of implant. Large mitral valves were at greatest risk of strut fracture, with the largest mitral valves (33 mm) estimated to be 33 times more likely to fracture than the smallest (21 to 25 mm) aortic valves. Date of manufacture was also associated with risk; valves welded from mid-1981 through March 1984 were more likely to fracture than those manufactured in 1979 and 1980. Body surface area <1.5 m
2
was associated with 1/16 the risk of body surface area ≥2.0 m
2
. No other patient factor was strongly associated with the risk of strut fracture.

Conclusions
Few patient features identifiable in the implant record are predictive of strut fracture. Our analysis supports previous work in identifying valve size, patient age, and date of manufacture as predictors of fracture and adds body surface area. A number of these associations suggest that conditions associated with higher cardiac output may also place patients at increased risk.
Influence of the Implantable Cardioverter/Defibrillator on Sudden Death and Total Mortality in Patients Evaluated for Cardiac Transplantation
Authors: Sweeney Michael O. , Ruskin Jeremy N. , Garan Hasan , McGovern Brian A. , Guy Mary L. , Torchiana David F. , Vlahakes Gus J. , Newell John B. , Semigran Marc J. , Dec G. William
Published: June 2012

Background
Implantable cardioverter/defibrillators (ICDs) may reduce sudden tachyarrhythmic death in patients with severe left ventricular dysfunction. It is uncertain whether this improves survival, particularly in patients awaiting cardiac transplantation.

Methods and Results
The effect of treatment for spontaneous ventricular arrhythmias (ICD [n=59], antiarrhythmic drugs [n=53], or no antiarrhythmic treatment [n=179]) on total mortality and mode of cardiac death was analyzed in 291 consecutive patients evaluated for cardiac transplantation between January 1986 and January 1995. There were 109 deaths (37.4%) (63 [21.6%] sudden, 40 [13.7%] nonsudden, and 6 [2.1%] noncardiac) during mean follow-up of 15 months (range, 1 to 118 months). Baseline clinical variables, medical therapies for heart failure, and actuarial rates of transplantation were similar between treatment groups. Kaplan-Meier sudden death rates were lowest in the ICD group, intermediate in the no antiarrhythmic treatment group, and highest in the drug treatment group throughout follow-up (12-month sudden death rates, 9.2%, 16.0%, and 34.7%, respectively;
P
=.004). Total mortality and nonsudden death rates did not differ. Cox proportional-hazards model revealed that antiarrhythmic drug treatment was associated with sudden death (relative risk, 2.1; 95% CI, 1.04 to 3.39;
P
=.04) and ICD was associated with nonsudden death (relative risk, 2.26; 95% CI, 1.12 to 4.62;
P
=.02).

Conclusions
Sudden death rates were lowest in patients treated with ICDs compared with drug treatment or no antiarrhythmic treatment. However, although ICDs reduced sudden death in selected high-risk patients with severe left ventricular dysfunction, the effect on long-term survival was limited, principally by high nonsudden death rates.
Dobutamine-Atropine Stress Echocardiography in Asymptomatic Healthy Individuals
Authors: Carstensen Steen , Ali Samir M. , Stensgaard-Hansen Frank V. , Toft Jens , Haunsø Stig , Kelbæk Henning , Saunamäki Kari
Published: June 2012

Background
Interpretation of dobutamine-atropine stress echocardiography (DASE) is based on the assumption that the normal response to dobutamine-atropine infusion is characterized by increased systolic thickening and motion of the left ventricular (LV) walls, whereas a reduction or no change is considered indicative of coronary artery disease. The aim of this study was to quantitatively assess changes in LV dimension and wall motion patterns during DASE in a healthy population.

Methods and Results
Forty-two asymptomatic voluntary subjects (22 men) with a mean age of 59 years (range, 31 to 79 years) and a likelihood of <5% for coronary artery disease underwent DASE with digital recording of two-dimensional and M-mode echocardiography at baseline and low-dose and peak infusion rates. Mean end-diastolic and end-systolic LV diameters and areas decreased and wall thicknesses increased progressively throughout the test. Wall motion and thickening increased from baseline to low-dose infusion in nearly all subjects. However, from low-dose to peak infusion, the mean absolute wall motion and relative wall thickening decreased by 13.1% (95% CI, 2.7 to 23.5) and 21.4% (95% CI, 6.4 to 36.4) regardless of age, sex, or use of atropine. Changes in fractional shortening and absolute wall thickening varied considerably, with a decrease observed in 15 and 13 individuals (36% and 31%), respectively.

Conclusions
In healthy subjects, measures of wall motion and wall thickening increased from baseline to low-dose infusion but decreased from low-dose to peak infusion. These findings call for revision of the assumptions on which the common analysis of DASE is based.