bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Calcification in Coronary Artery Disease
Authors: Mintz Gary S. , Popma Jeffrey J. , Pichard Augusto D. , Kent Kenneth M. , Satler Lowell F. , Chuang Ya Chien , Ditrano Christine J. , Leon Martin B.
Published: June 2012

Background
Target lesion calcium is a marker for significant coronary artery disease and a determinant of the success of transcatheter therapy.

Methods and Results
Eleven hundred fifty-five native vessel target lesions in 1117 patients were studied by intravascular ultrasound (IVUS) and coronary angiography. The presence, magnitude, location, and distribution of IVUS calcium were analyzed and compared with the detection and classification (none/mild, moderate, and severe) by angiography. Angiography detected calcium in 440 of 1155 lesions (38%): 306 (26%) moderate calcium and 134 (12%) severe. IVUS detected lesion calcium in 841 of 1155 (73%,
P
<.0001 versus angiography). The mean arc of lesion calcium measured 115±110°; the mean length measured 3.5±3.7 mm. Target lesion calcium was only superficial in 48%, only deep in 28%, and both superficial and deep in 24%. The mean arc of superficial calcium measured 85±108°; the mean length measured 2.4±3.4 mm. Three hundred seventy-three of 1155 reference segments (32%) contained calcium (
P
<.0001 compared with lesion site). The mean arc of reference calcium measured 42±80°; the mean length measured 1.7±3.6 mm. Only 44 (4%) had reference calcium in the absence of lesion calcium. Angiographic detection and classification of calcium depended on arcs, lengths, location, and distribution of lesion and reference segment calcium. By discriminant analysis, the classification function for predicting angiographic calcium included the arc of target lesion calcium, the arc of superficial calcium, the length of reference segment calcium, and the location of calcium within the lesion. This model correctly predicted the angiographic detection of calcification in 74.4% of lesions and the angiographic classification (none/moderate/severe) of calcium in 62.8% of lesions.

Conclusions
IVUS detected calcium in >70% of lesions, significantly more often than standard angiography. Although angiography is moderately sensitive for the detection of extensive lesion calcium (sensitivity, 60% and 85% for three- and four-quadrant calcium, respectively), it is less sensitive for the presence of milder degrees.
A Multicenter, Randomized Trial of Coronary Angioplasty Versus Directional Atherectomy for Patients With Saphenous Vein Bypass Graft Lesions
Authors: Holmes David R. , Topol Eric J. , Califf Robert M. , Berdan Lisa G. , Leya Ferdinand , Berger Peter B. , Whitlow Patrick L. , Safian Robert D. , Adelman Allan G. , Kellett Mirle A. , Talley J. David , Shani Jacob , Gottlieb Ronald S. , Pinkerton Cass A. , Lee Kerry L. , Keeler Gordon P. , Ellis Stephen G.
Published: June 2012

Background
Directional coronary atherectomy and percutaneous transluminal coronary angioplasty have both been used in symptomatic patients with coronary saphenous vein bypass graft stenoses. The relative merits of plaque excision and removal versus balloon dilatation remain uncertain. We compared outcomes after directional coronary atherectomy or angioplasty in patients with de novo bypass graft stenoses.

Methods and Results
Fifty-four North American and European sites randomized 305 patients with de novo vein graft lesions to atherectomy (n=149) or angioplasty (n=156). Quantitative coronary angiography at a core laboratory assessed initial and 6-month results. Initial angiographic success was greater with atherectomy (89.2% versus 79.0%), as was initial luminal gain (1.45 versus 1.12 mm,
P
<.001). Distal embolization was increased with atherectomy (
P
=.012), and a trend was shown toward more non–Q-wave myocardial infarction (
P
=.09). Although the 6-month net minimum luminal diameter gain was 0.68 mm for atherectomy and 0.50 mm for angioplasty, the restenosis rates were similar, 45.6% for atherectomy and 50.5% for angioplasty (
P
=.491). At 6 months, there was a trend toward decreased repeated target-vessel interventions for atherectomy (
P
=.092); in addition, 13.2% of patients treated with atherectomy versus 22.4% of the angioplasty patients (
P
=.041) required repeated percutaneous intervention of the initial target lesion.

Conclusions
Atherectomy of de novo vein graft lesions was associated with improved initial angiographic success and luminal diameter but also with increased distal embolization. There was no difference in 6-month restenosis rates, although primary atherectomy patients tended to require fewer target-vessel revascularization procedures.
Aging and Endothelial Function in Normotensive Subjects and Patients With Essential Hypertension
Authors: Taddei Stefano , Virdis Agostino , Mattei Paola , Ghiadoni Lorenzo , Gennari Alessandra , Fasolo Ciro Basile , Sudano Isabella , Salvetti Antonio
Published: June 2012

Background
Experimental data from normotensive and hypertensive animals indicate that aging is associated with impaired endothelium-dependent relaxations to acetylcholine, and this possibility appears to be confirmed in the human coronary artery. In the present study, we evaluated the effect of age on endothelial responsiveness in the forearm vessels of either normotensive control subjects or essential hypertensive patients.

Methods and Results
Within the normotensive or hypertensive group (n=53 and n=57, respectively), subjects were selected with similar blood pressure, plasma cholesterol, and glucose values, and hypercholesterolemic subjects, diabetics, and smokers were excluded. We evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 μg/100 mL per minute), an endothelium-independent vasodilator. Acetylcholine caused a dose-dependent vasodilation that was significantly (
P
<.01) lower in essential hypertensive patients than in normotensive control subjects. However, a significant negative correlation was observed between acetylcholine-induced vasodilation and patient age in both normotensive (
r
=−.86,
P
<.001) and hypertensive (
r
=−.85,
P
<.001) patients. In contrast, vasodilation to sodium nitroprusside was similar in normotensive control subjects and essential hypertensive patients with a poorer inverse correlation with patient age (normotensive control subjects,
r
=−.37; hypertensive patients,
r
=−.36) compared with acetylcholine.

Conclusions
The present data indicate that there is a blunted response to acetylcholine with advancing age in both normotensive control subjects and essential hypertensive patients, suggesting that aging is associated with reduced endothelium-dependent vasodilation in humans.
Histomorphometric and Biochemical Correlates of Arterial Procollagen Gene Expression During Vascular Repair After Experimental Angioplasty
Authors: Karim M. Asad , Miller D. Douglas , Farrar Melody A. , Eleftheriades Elias , Reddy Bouyella H. , Breland Clyniece M. , Samarel Allen M.
Published: June 2012

Background
To determine the transcriptional, biochemical, and histomorphometric correlates of neointimal procollagen accumulation during arterial repair after balloon angioplasty of atherogenic vessels, rabbit iliac artery collagen content and the induction of α
1
(I) and α
1
(III) procollagen mRNA were assessed in normal vessels and at 2, 7, and 30 days after angioplasty.

Methods and Results
Quantitative iliac artery histomorphometric neointimal collagen analysis was performed using a specific picrosirius red stain under polarized light. Arterial cross-sectional area reduction, total cellularity, and vascular smooth muscle cell density (per 10
4
μ
2
of neointima) were quantified in routine and immunohistochemically stained sections (α-actin and RAM-11), from which biochemical concentrations of tissue protein, RNA, and DNA were also measured. Collagen comprised 0.23±0.1 mg/mg of total protein in the normal vessel wall and did not increase in vessels studied 2 and 7 days after angioplasty (0.26±0.06, 0.28±0.05 mg/mg of protein,
P
=NS). By 30 days after angioplasty, >50% of the protein concentration was collagen (0.55±0.11 mg/mg of protein,
P
=.02). Collagen-positive histological staining also increased significantly from 17±2% of the neointima at day 2 to 32±5% by day 30 (
P
=.01). The transcript regulatory signal for α
1
(I) procollagen mRNA was induced 2 days after angioplasty, peaking at 7 days for both α
1
(I) and α
1
(III), and returning to control levels 30 days after angioplasty. A significant luminal cross-sectional area reduction of the arterial wall was confirmed both by angiography and histomorphometry (
P
=.01). This was not associated with a significant change in α-actin (+) vascular smooth muscle cell density (38±7 nuclei per 10
4
μ
2
at day 2 and at day 30) or tissue DNA concentration (
P
=NS).

Conclusions
We conclude that procollagen genes are transcriptionally activated early (2 to 7 days) after angioplasty vessel injury and that collagen subsequently constitutes a major biochemical and histological component of the proliferative neointima by 30 days after angioplasty. Alterations in pathways regulating procollagen metabolism may also contribute to the accumulation of extracellular matrix and growth of the neointima in the late repair phase after vessel wall injury.
Gradual Onset of Myocardial Ischemia Results in Reduced Myocardial Infarction
Authors: Ito Bruce R.
Published: June 2012

Background
With moderate reductions in coronary blood flow, adjustments in myocardial metabolism can occur with a normalization of the imbalance between the decreased O
2
delivery and tissue O
2
demand. This state of “downregulated” metabolism is associated with reduced function and minimal irreversible injury and has been linked to myocardial hibernation. We hypothesized that (1) this process would occur when perfusion was reduced to severely ischemic levels, but only when flow declined at a slow rate rather than abruptly, and (2) this would result in blunted ischemia and reduced myocardial injury for a given period of low blood flow.

Methods and Results
The left anterior descending coronary artery in anesthetized open-chest pigs was cannulated and perfused with arterial blood by an extracorporeal perfusion pump. Regional function (percent segment shortening, %SS) was measured with sonomicrometry and a regional coronary vein cannulated for blood gas analysis and lactate measurements. Coronary blood flow (CBF) was reduced to 10% of control either in a step fashion (Fast Ischemia group) or gradually in a linear manner over 70 minutes (Ramp Ischemia group). In all animals, CBF was held for 60 minutes at this 10% level and then followed by 2 hours of reperfusion. In the Ramp Ischemia group, the linear fall in CBF resulted in an initial maintenance of both %SS and myocardial oxygen consumption (MV̇
o
2
) followed by linear decreases in both variables (
r
=.98 to .99) as flow fell to the 10% level. The relation of MV̇
o
2
to function was linear (
r
=.99) over the entire flow range. Although %SS, MV̇
o
2
, CBF, coronary pressure, and hemodynamics during the 10% flow period were not different between groups, the increases in coronary venous lactate and P
co
2
and fall in pH were blunted in the Ramp Ischemia group compared with the Fast Ischemia group. With reperfusion, a significant decrease in end-diastolic length was present only in the Fast Ischemia group. Additionally, although the region at risk was not different, infarction was markedly reduced in the Ramp Ischemia group (6.6±1.9%) compared with the Fast Ischemia group (31.4±6.9%).

Conclusions
These data are consistent with the hypothesis that the downregulation of myocardial metabolism with gradually decreased flow to severe levels results in reduced myocardial injury for a given period of low flow. We propose that the rate at which blood flow decreases with myocardial underperfusion is a novel determinant of infarct injury. This may have clinical implication in situations in which there is a time-dependent component to the decrease in coronary blood flow in acute ischemic events, ie, thrombus formation at a site of coronary stenosis.
Randomized Double-Blind Comparison of Two Doses of Hirulog With Heparin as Adjunctive Therapy to Streptokinase to Promote Early Patency of the Infarct-Related Artery in Acute Myocardial Infarction
Authors: Théroux Pierre , Pérez-Villa Félix , Waters David , Lespérance Jacques , Shabani Faryala , Bonan Raoul
Published: June 2012

Background
An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double- blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin.

Methods and Results
Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4±2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin (
P
=.006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively (
P
=.008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 (
P
=.046) and 92%, 68%, and 46% for TIMI flow grade 3 (
P
=.014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35;
P
<.001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51;
P
=.04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups.

Conclusion
Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.
A Novel and Rapid Whole-Blood Assay for D-Dimer in Patients With Clinically Suspected Deep Vein Thrombosis
Authors: Wells Philip S. , Brill-Edwards Patrick , Stevens Pamela , Panju Akbar , Patel Ameen , Douketis James , Massicotte M. Patricia , Hirsh Jack , Weitz Jeffrey I. , Kearon Clive , Ginsberg Jeffrey S.
Published: June 2012

Background
The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT).

Methods and Results
All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients.

Conclusions
The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.
Limitations and Late Complications of Third-Generation Automatic Cardioverter-Defibrillators
Authors: Nunain S. O. , Roelke M. , Trouton T. , Osswald S. , Kim Y. H. , Sosa-Suarez G. , Brooks D. R. , McGovern B. , Guy M. , Torchiana D. F. , Vlahakes G. J. , Garan H. , Ruskin J. N.
Published: June 2012

Background
This study examines the limitations and complex management problems associated with the use of tiered-therapy, implantable cardioverter-defibrillators (ICDs).

Methods and Results
The study group comprises the first 154 patients undergoing implantation of tiered-therapy ICDs at our institution. Pulse generators from three different manufacturers were used. In 39 patients, a complete nonthoracotomy lead system was used. The perioperative mortality was 1.3%. Of these 154 patients, 37% experienced late postoperative problems. Twenty-one patients required system revision within 36.5 months (mean, 8.57±11.3) of surgery. Reasons for revision were spurious shocks due to electrode fractures (3) or electrode adapter malfunction (2), inadequate signal from endocardial rate-sensing electrodes (3), superior vena cava or right ventricular coil migration (5), failure to correct tachyarrhythmias due to a postimplant rise in defibrillation threshold (5), or pulse generator failure (3). One of these patients required system removal for infection after revision of an endocardial lead. A further 32 patients received inappropriate shocks for atrial fibrillation with a rapid ventricular response or sinus tachycardia. Two of these patients also received shocks for ventricular tachycardia initiated by antitachycardia pacing triggered by atrial fibrillation. Ventricular pacing for bradycardia was associated with inappropriate shocks due to excessive autogain in 2 patients.

Conclusions
Despite the major diagnostic and therapeutic advantages of tiered-therapy ICDs, a significant proportion of patients continue to experience hardware-related complications or receive inappropriate shocks.
Reverse Remodeling From Cardiomyoplasty in Human Heart Failure
Authors: Kass David A. , Baughman Kenneth L. , Pak Peter H. , Cho Peter W. , Levin Howard R. , Gardner Timothy J. , Halperin Henry R. , Tsitlik Joshua E. , Acker Michael A.
Published: June 2012

Background
Cardiomyoplasty (CM) is a novel surgical therapy for dilated cardiomyopathy. In this procedure, the latissimus dorsi muscle is wrapped around the heart and chronically paced synchronously with ventricular systole. While studies have found symptomatic improvement from this therapy, the mechanisms by which CM confers benefit remain uncertain. This study sought to better define these mechanisms by means of serial pressure-volume relation analysis.

Methods and Results
Serial pressure-volume studies were performed by the conductance catheter method in three patients (total to date) with dilated cardiomyopathy (New York Heart Association class III) who underwent CM. Data were measured at baseline (before surgery) and at 6 and 12 months after CM. Chronic left ventricular (LV) systolic and diastolic changes induced by CM were evaluated with the stimulator in its stable pacing mode (every other beat) and after temporarily suspending pacing. CM-stimulated beats were compared with pacing-off beats to evaluate active systolic assist effects of CM. In each patient, CM resulted in a chronic lowering of cardiac end-diastolic volume and an increased ejection fraction. Most notably, the end-systolic pressure-volume relation shifted leftward, consistent with reversal of chronic chamber remodeling. In contrast, the diastolic pressure-volume relation was minimally altered, and the loops shifted down along the same baseline relation. These marked chronic changes in LV function measurable with CM stimulation off contrasted to only minor acute effects observed when the muscle wrap was activated. This suggests that the benefit of CM derived less from active systolic assist than from remodeling, perhaps because of an external elastic constraint.

Conclusions
These data, while limited to a small number of patients, suggest that CM can reverse remodeling of the dilated failing heart. While systolic squeezing assist effects of CM may play a role in some patients, our study found that this was not required to achieve substantial benefits from the procedure. We speculate that CM may act more passively, like an elastic girdle around the heart, to help reverse chamber remodeling.
Long-term Temporal Patterns of Ventricular Tachyarrhythmias
Authors: Wood Mark A. , Simpson Pippa M. , Stambler Bruce S. , Herre John M. , Bernstein Robert C. , Ellenbogen Kenneth A.
Published: June 2012

Background
Technological limitations have precluded investigation of long-term temporal patterns of ventricular tachyarrhythmia recurrences. Newer implantable cardioverter-defibrillators permit such analyses by accurately recording the time and date of tachycardia detections during long-term follow-up. This study tests the hypothesis that ventricular tachycardia occurrences are randomly distributed over time in individual patients.

Methods and Results
The time and date of 727 episodes of ventricular tachyarrhythmias were recorded from the data logs of 31 patients with implantable cardioverter-defibrillators followed for a median of 177 days (range, 7 to 782 days). All patients had three or more ventricular tachycardia detections and no detections from causes other than ventricular arrhythmias. In 28 of 31 patients, the distribution of the interdetection time intervals during follow-up differed significantly (all
P
<.01) from an exponential model distribution of interdetection intervals that assumed that detections were equally likely to occur at any time during follow-up (random). The Kolmogorov-Smirnov goodness-of-fit test was used to compare sample and model distributions. In each patient, the nonrandom distributions resulted from a preponderance of interdetection time intervals that were shorter than predicted by the random model, resulting in a temporal clustering of arrhythmic events. The interdetection interval was ≤1 hour and ≤91 hours for 55% and 78% of all intervals, respectively. When only those episodes receiving shock or antitachycardia pacing therapy were analyzed, 25 of 29 patients still manifested nonrandom distributions (all
P
<.01). When only episodes with tachycardia rates >240 beats per minute were analyzed, 11 of 13 patients manifested nonrandom distributions (all
P
<.01).

Conclusions
Ventricular tachycardia detections and delivered antitachycardia therapies by implantable cardioverter-defibrillators are nonrandomly distributed throughout long-term follow-up in the majority of patients. The temporal clustering of these arrhythmic events may allow preemptive antiarrhythmic therapy and should be considered in the design of therapy based on suppression of spontaneous ventricular arrhythmias to statistically derived end points.
Heterogeneities in [K
+
]
o
and TQ Potential and the Inducibility of Ventricular Fibrillation During Acute Regional Ischemia in the Isolated Perfused Porcine Heart
Authors: Coronel Ruben , Wilms-Schopman Francien J. G. , Dekker Lukas R. C. , Janse Michiel J.
Published: June 2012

Background
The relation between the inducibility of ventricular fibrillation (VF) and heterogeneity of the extracellular potassium concentration ([K
+
]
o
) and of TQ potential is unknown.

Methods and Results
Data from 78 epicardial DC electrodes or from up to 32 intramural K
+
electrodes were acquired simultaneously. Induction of VF was attempted with one or two ventricular premature beats induced in normal myocardium in isolated porcine hearts during (1) regional perfusion of the left anterior descending artery (LAD) with a normoxic, hyperkalemic solution ([K
+
] 6 to 19.6 mmol/L), (2) simulated ischemia, ie, LAD perfusion with a glucose-free, hypoxic solution ([K
+
] 4 to 16 mmol/L, P
o
2
<5 mm Hg, pH 6.98), and (3) regional ischemia produced by stopping LAD flow. During normoxic, hyperkalemic LAD perfusion, no VF could be induced (12 interventions, 7 hearts). During simulated ischemia (27 interventions), VF could be induced only when [K
+
]
o
was between 8 and 13.5 mmol/L. After 5 minutes of true regional ischemia, more sites with [K
+
]
o
between 8 and 13.5 mmol/L were present than after 10 minutes. VF could be induced with 1 ventricular premature beat in 11 of 17 interventions after 5 minutes and in 0 of 14 interventions after 10 minutes of ischemia (
P
<.001). Regional simulated ischemia presents a relatively homogeneous condition compared with 5 minutes of regional ischemia (SD±SEM of TQ potential in LAD tissue, 0.9±0.05 versus 2.1±0.13 mV, respectively). True ischemia superimposed on regional simulated ischemia caused the rapid development of heterogeneities in [K
+
]
o
and TQ potential and caused VF after 45±7 seconds in all interventions. Activation maps of induction of VF suggest a different mechanism of unidirectional block during simulated ischemia from that in true ischemia.

Conclusions
(1) In the presence of hypoxia and acidosis, [K
+
]
o
between 8 and 13.5 mmol/L provides the conditions necessary for the induction of VF; (2) after 5 minutes of ischemia, these conditions are present in a larger area and inducibility of VF is higher than after 10 minutes of ischemia; and (3) small heterogeneities within the intermediate K
+
–concentration domain (8 to 13.5 mmol/L) are associated with high inducibility of VF.
Quantitative Measurements of Cardiac Phosphorus Metabolites in Coronary Artery Disease by
31
P Magnetic Resonance Spectroscopy
Authors: Yabe Takahiro , Mitsunami Kenichi , Inubushi Toshiro , Kinoshita Masahiko
Published: June 2012

Background
31
P metabolite measurements in the human heart by magnetic resonance spectroscopy (MRS) have been reported previously. By use of a method in which metabolite content was quantified with reference to a standard located outside the chest, it has become possible to measure the content of phosphocreatine (PCr) and ATP in vivo in the human heart. In this study, PCr and ATP contents were measured by
31
P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy.

Methods and Results
Forty-one subjects with stenosis of the left anterior descending coronary artery (>50%) and 11 healthy control subjects (C) composed the present study group. Patients were divided into two groups on the basis of exercise
201
Tl scintigraphy: a reversible
201
Tl defect group (RD[+], n=29) who demonstrated redistribution at late image and a fixed
201
Tl defect group (RD[−], n=12). While the subjects lay supine within the magnet,
31
P MR spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected one-dimensional chemical shift imaging. For metabolite quantification, a standard was placed at the center of the surface coil. ANOVA revealed significant differences among the three groups with respect to the mean (±SD) PCr at rest (C, 12.14±4.25 >RD[+], 7.64±3.00 >RD[−], 3.94±2.21 μmol/g wet heart tissue,
P
<.05) as well as a significant decrease in ATP in the RD(−) group (C, 7.72±2.97; RD[+], 6.35±3.17 >RD[−], 4.35±1.52 μmol/g wet heart tissue,
P
<.05).

Conclusions
Compared with healthy control subjects, PCr content decreased significantly in patients with both reversible and fixed
201
Tl defects, and ATP content decreased significantly in subjects with fixed thallium defects. These results suggest that the measurement of ATP content in the human heart by
31
P MRS is a clinically important method for the evaluation of myocardial viability.
Electrophysiological Manifestations of the Excitable Gap of Slow-Fast AV Nodal Reentrant Tachycardia Demonstrated by Single Extrastimulation
Authors: Lai Wen-Ter , Lee Chee-Siong , Sheu Sheng-Hsiung , Hwang Yeo-Shin , Sung Ruey J.
Published: June 2012

Background
Although AV nodal reentrant tachycardia (AVNRT) is a well-known rhythm disorder, its anatomic substrate and electrophysiological mechanism remain to be defined. Previously, the description of the excitable gap (EG) of AVNRT was based on electrical stimulation performed from sites remote from the reentrant circuit. In the present study, we characterized the EG of AVNRT by atrial extrastimulation close to the putative reentrant circuit in the AV junction.

Methods and Results
In 16 patients (3 men, 13 women; mean age, 45±13 years) with inducible slow-fast AVNRT (mean cycle length, 353±52 ms), single extrastimuli with a 10-ms decrement in the premature coupling interval were delivered from the anterosuperior interatrial septum (fast pathway area) and the posteroinferior interatrial septum (slow pathway area) from late diastole until atrial refractoriness. An EG was considered present when resetting or termination of AVNRT was induced by single atrial extrastimulation. The study showed that the duration of the EG of AVNRT was wide, measuring 121±56 and 123±47 ms and occupying 33±11% and 34±9% of the tachycardia cycle length during single extrastimulation from the slow pathway area and the fast pathway area, respectively. The resetting pattern most commonly manifested as the sum of the coupling interval and the return cycle being less than a fully compensatory pause (two times the basic tachycardia cycle length). However, patterns equal to and greater than a fully compensatory pause were also observed. Of note, in 2 of the 16 patients, atrial extrastimulation from either the fast or slow pathway area also affected the preceding tachycardia cycle length (HH interval), indicating alteration of the anterograde input. In all patients, the curve derived from plotting the coupling interval of extrastimuli against the return cycle during resetting exhibited an “increasing” pattern. The mode of tachycardia termination usually occurred when the premature atrial impulse was orthodromically blocked in the anterograde slow pathway.

Conclusions
The EG of slow-fast AVNRT is relatively wide, as demonstrated by single atrial extrastimulation from the interatrial septum near the AV junction. Overall, the electrophysiological manifestations of the EG of AVNRT are very similar to those described in AV reciprocating tachycardia incorporating an accessory connection. These findings lend further support to the notion that, in humans, AVNRT involves a reentrant mechanism with a wide excitable gap.
Angiotensin II Type 1 Receptor Blockade Inhibits the Expression of Immediate-Early Genes and Fibronectin in Rat Injured Artery
Authors: Kim Shokei , Kawamura Masaki , Wanibuchi Hideki , Ohta Kensuke , Hamaguchi Akinori , Omura Takashi , Yukimura Tokihito , Miura Katsuyuki , Iwao Hiroshi
Published: June 2012

Background
Vascular injury activates various kinds of genes, including proto-oncogenes, growth factors, and extracellular matrix proteins. However, the significance of activation of these genes in neointimal formation is poorly understood. Angiotensin II type 1 (AT
1
) receptor antagonist is shown to prevent neointimal formation after vascular injury, although the mechanism is unclear. To understand the molecular mechanism of vascular thickening, we examined the effects of AT
1
receptor blockade on the gene expression of proto-oncogenes, transforming growth factor–β
1
(TGF-β
1
), and extracellular matrix proteins after vascular injury.

Methods and Results
Endothelial denudation of the left common carotid artery in Sprague-Dawley rats was performed with a Fogarty 2F balloon catheter. TCV-116 (10 mg · kg
−1
· d
−1
), a selective nonpeptide AT
1
receptor antagonist, or vehicle was administered orally to rats from 1 day before to 14 days after balloon injury. Injured left and uninjured right common carotid arteries were removed from rats at 1, 6, and 24 hours and 3, 7, and 14 days after balloon injury. Tissue mRNA levels were measured with Northern blot analysis using specific cDNA probes and corrected for 18
S
ribosomal RNA value. Arterial mRNAs for c-
fos
, c-
jun
,
jun
B,
jun
D, and
Egr
-1 increased significantly at 1 hour after balloon injury and decreased rapidly. At 6 hours, ornithine decarboxylase (ODC) mRNA expression reached the maximal levels. TGF-β
1
and fibronectin mRNA levels started to increase at 6 hours after injury and remained enhanced until 7 days after injury. On the other hand, collagen types I, III, and IV and laminin mRNA levels were not significantly increased over 7 days. Treatment with TCV-116 significantly inhibited the induction of mRNAs for c-
fos
, c-
jun
,
Egr
-1, ODC, and fibronectin in injured artery, whereas the increase in TGF-β
1
gene expression after injury was not prevented by TCV-116. Immunohistological studies indicated that TCV-116 decreased not only the intimal thickening but also the amount of these extracellular matrix proteins in the intima.

Conclusions
The results indicate that AT
1
receptor blockade inhibits the induction of immediate-early genes, ODC, and fibronectin in rat injured artery. Thus, inhibition of intimal thickening by AT
1
receptor blockade may be mediated at least in part by suppression of multiple genes related to cell growth and migration in the very early phase after vascular injury.
Factor V Leiden and Risks of Recurrent Idiopathic Venous Thromboembolism
Authors: Ridker Paul M. , Miletich Joseph P. , Stampfer Meir J. , Goldhaber Samuel Z. , Lindpaintner Klaus , Hennekens Charles H.
Published: June 2012

Background
Whether Leiden mutation in the gene coding for coagulation factor V is associated with recurrent idiopathic venous thromboembolism (VTE) is unknown, but such data are necessary to evaluate the merits of genetic screening in secondary prevention of thromboembolic disease.

Methods and Results
Among 14 916 apparently healthy men who provided DNA samples and were followed in the Physicians’ Health Study through August 1994, 77 suffered an idiopathic VTE. These 77 men were followed for an additional average period of 68.3 months, during which time 11 (14.3%) suffered a recurrent idiopathic VTE. Factor V Leiden status was assessed in these men, and incidence rates of recurrence were calculated by genotype. All recurrent events occurred after cessation of anticoagulation. Seven recurrences occurred among 63 genetically unaffected subjects (11.1%; incidence rate, 1.82 per 100 person-years), while four occurred among those 14 heterozygous for factor V Leiden (28.6%; incidence rate, 7.46 per 100 person-years). Thus, factor V Leiden was associated with a fourfold to fivefold increase in risk of recurrent VTE (crude relative risk, 4.1;
P
=.04; age- and smoking-adjusted relative risk, 4.7;
P
=.047). There was no difference in mean time between index and recurrent events by genotype. Among heterozygous men, 76% of recurrent events were attributable to mutation.

Conclusions
In prospective evaluation of 77 men with a history of idiopathic VTE, factor V Leiden was associated with a fourfold to fivefold increased risk of recurrent thrombosis. These data raise the possibility that patients with VTE affected by factor V Leiden may require more prolonged anticoagulation to prevent recurrent disease compared with those without mutation.
Aspirin in the Treatment of Acute Myocardial Infarction in Elderly Medicare Beneficiaries
Authors: Krumholz Harlan M. , Radford Martha J. , Ellerbeck Edward F. , Hennen John , Meehan Thomas P. , Petrillo Marcia , Wang Yun , Kresowik Timothy F. , Jencks Stephen F.
Published: June 2012

Background
Although aspirin is an effective, inexpensive, and safe treatment of acute myocardial infarction, the frequency of use of aspirin in actual medical practice is not known. Elderly patients, a group with low rates of utilization of effective therapies such as thrombolytic therapy, also may be at risk of not receiving aspirin for acute myocardial infarction. To address this issue, we sought to determine the current pattern of aspirin use and to assess its effectiveness in a large, population-based sample of elderly patients hospitalized with acute myocardial infarction.

Methods and Results
As part of the Cooperative Cardiovascular Project Pilot, a Health Care Financing Administration initiative to improve quality of care for Medicare beneficiaries, we abstracted hospital medical records of Medicare beneficiaries who were hospitalized in Alabama, Connecticut, Iowa, or Wisconsin from June 1992 through February 1993. Among the 10 018 patients ≥65 years old who had no absolute contraindications to aspirin, 6140 patients (61%) received aspirin within the first 2 days of hospitalization. Patients who were older, had more comorbidity, presented without chest pain, and had high-risk characteristics such as heart failure and shock were less likely to receive aspirin. The use of aspirin was significantly associated with a lower mortality (OR, 0.78; 95% CI, 0.70 to 0.89) after adjustment for potential confounders.

Conclusions
About one third of elderly patients with acute myocardial infarction who had no contraindications to aspirin therapy did not receive it within the first 2 days of hospitalization. The elderly patients with the highest risk of death were the least likely to receive aspirin. After adjustment for differences between the treatment groups, the use of aspirin was associated with 22% lower odds of 30-day mortality. The increased use of aspirin for patients with acute myocardial infarction is an excellent opportunity to improve the delivery of care to elderly patients.
Comparison of Myocardial Contrast Echocardiography and Low-Dose Dobutamine Stress Echocardiography in Predicting Recovery of Left Ventricular Function After Coronary Revascularization in Chronic Ischemic Heart Disease
Authors: deFilippi Christopher R. , Willett DuWayne L. , Irani Waleed N. , Eichhorn Eric J. , Velasco Carlos E. , Grayburn Paul A.
Published: June 2012

Background
Dobutamine stress echocardiography (DSE) and myocardial contrast echocardiography (MCE) can predict recovery of left ventricular function after myocardial infarction. DSE also has been shown to predict left ventricular functional recovery after revascularization in chronic ischemic heart disease, whereas MCE has not been evaluated in such patients. This study was performed to compare DSE and MCE in the prediction of left ventricular functional recovery after revascularization in patients with chronic ischemic heart disease.

Methods and Results
MCE and DSE were performed in 35 patients with chronic coronary artery disease and significant wall motion abnormalities (mean ejection fraction, 0.36±0.09). Regional wall motion was scored by use of a 16-segment model wherein 1=normal or hyperkinetic, 2=hypokinetic, 3=akinetic, and 4=dyskinetic. Each segment was evaluated for contractile reserve by DSE and perfusion by MCE. Revascularization (coronary artery bypass graft [n=13] and percutaneous transluminal coronary angioplasty [n=10]) was successful in 23 patients. Follow-up echocardiograms were done to assess wall motion 30 to 60 days later. In 238 segments with resting wall motion abnormalities, perfusion was more likely to present than contractile reserve (97% versus 91%,
P
<.02). Revascularization resulted in functional recovery in 77 of 95 hypokinetic segments (81%) but only 18 of 57 akinetic segments (32%,
P
<.0001). DSE and MCE were not significantly different in predicting functional recovery of hypokinetic segments. In akinetic segments, DSE and MCE had similar sensitivities (89% versus 94%, respectively) and negative predictive values (93% and 97%, respectively) in predicting functional recovery. However, DSE had a higher specificity (92% versus 67%,
P
<.02) and positive predictive value (85% versus 55%,
P
<.02) than MCE in predicting functional recovery.

Conclusions
Both contractile reserve by DSE and perfusion by MCE are predictive of functional recovery in hypokinetic segments after coronary revascularization in patients with chronic coronary artery disease. In akinetic segments, myocardial perfusion by MCE may exist in segments that do not recover contractile function after revascularization. Thus, contractile reserve during low-dose dobutamine infusion is a better predictor of functional recovery after revascularization in akinetic segments than perfusion.
Progesterone Receptor Expression in Human Saphenous Veins
Authors: Perrot-Applanat M. , Cohen-Solal K. , Milgrom E. , Finet M.
Published: June 2012

Background
Clinical and epidemiological observations regarding varicose veins, such as their predominance in women and the occurrence of venous stasis during sex-hormone therapy, the luteal phase of the menstrual cycle, and pregnancy, suggest a sex hormone–dependency of this venous pathology. In the present study, analysis of steroid receptors was used to determine if these effects were due to a direct hormonal action on the saphenous vein.

Methods and Results
Biopsy samples were obtained from patients undergoing stripping removal of varicose saphenous veins. Patients were men (n=5) and premenopausal (n=15) or postmenopausal (n=10) women. Progesterone receptors (PR) and estrogen receptors (ER) were determined by both enzyme immunoassay (EIA) and immunocytochemistry by use of monoclonal antibodies. Ninety percent of the biopsy samples showed PR positivity by EIA (range, 5 to 53 fmol/mg cytosol protein). When present, PR staining was observed in the cell nuclei of the tunica media and the subendothelial layer (neointima). No significant variation was observed in the PR content of different regions within the same saphenous vein. In contrast, no ER or extremely low levels of ER (<5 fmol/mg cytosol protein) were detected by EIA in 25 of 30 varicose biopsy samples. Reverse transcription–polymerase chain reaction (RT-PCR) was used to analyze PR and ER mRNAs in biopsy samples that were PR positive/ER negative. With primers to the hormone-binding region encoded by PR mRNA, a RT-PCR product of the expected size was detected and its identity confirmed by Southern blot by use of a PR cDNA probe. In contrast, no RT-PCR product could be detected by use of primers to the DNA-binding domain, the hinge region, and the ligand-binding domain encoded by ER mRNA.

Conclusions
These results indicate that human saphenous veins from both sexes express PR, as previously described for arterial blood vessels. This observation suggests that progesterone acts directly on these veins via a classic receptor-mediated pathway.
Vascular Injury, Repair, and Restenosis After Percutaneous Transluminal Angioplasty in the Atherosclerotic Rabbit
Authors: Wilensky Robert L. , March Keith L. , Gradus-Pizlo Irmina , Sandusky George , Fineberg Naomi , Hathaway David R.
Published: June 2012

Background
Several nonatherosclerotic animal models of restenosis exist and are used for the evaluation of the vascular response to angioplasty-induced injury. However, few studies have evaluated the response of an atherosclerotic vessel to angioplasty. The present study examined the radiographic, histological, immunohistochemical, and morphometric responses over time of atherosclerotic rabbit femoral arteries after percutaneous transluminal angioplasty (PTA).

Methods and Results
Rabbits (n=94) underwent arterial desiccation and were fed a hypercholesterolemic diet for 3 weeks, and then PTA was performed. Arteries were obtained before PTA and 1, 3, 5, 7, 14, and 28 days after PTA. PTA caused radial stretching of the artery, medial compression, intramural hemorrhage, injury to normal arterial segments, and dissection within the intima and media. Thrombus filled and cellular accumulation repaired the dissection. Peak smooth muscle cell and macrophage DNA synthesis was noted at 3 to 5 days after angioplasty, generally at the dissection but also in normal sections of the artery. Adventitial injury and subsequent adventitial cellular proliferation and collagen production were observed. A rapid decrease in the radiographic minimal luminal diameter was noted at 3 days, resulting from vascular recoil or thrombus filling the dissection. At 7 to 14 days, only 24% to 33% of the luminal loss was accounted for by an increase in the intimal area, and 22% to 28% of the intima was neointima.

Conclusions
Restenosis in an atherosclerotic artery results from a variable combination of intimal proliferation, vascular remodeling/wound contraction, and recoil of the normal section of the artery. The variability of an atherosclerotic artery to PTA injury results from variable dissection, thrombus formation, and cellular response to injury as well as variable scar contraction and elastic recoil.
The Ib Phase of Ventricular Arrhythmias in Ischemic In Situ Porcine Heart Is Related to Changes in Cell-to-Cell Electrical Coupling
Authors: Smith William T. , Fleet William F. , Johnson Timothy A. , Engle Connie L. , Cascio Wayne E.
Published: June 2012

Background
This study was designed to test the hypothesis that the loss of cell-to-cell electrical interaction during ischemia modulates the amplitude of ischemia-induced TQ-segment depression (ie, the injury potential) and the occurrence of ventricular fibrillation (VF) during the so-called Ib phase of ventricular arrhythmias.

Methods and Results
Regional ischemia was induced by 60 minutes of mid–left anterior descending coronary artery ligation in open-chest swine (n=10). Cell-to-cell electrical uncoupling was defined as the onset of the terminal rise in whole-tissue resistivity (R
t
). Local activation times and TQ-segment changes (injury potential) were determined from unipolar electrograms. Extracellular K
+
([K
+
]
e
) and pH (pH
e
) were measured with plunge-wire ion-selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence of VF was positively correlated to the onset of cell-to-cell electrical uncoupling (
R
2
=.885). Cell-to-cell electrical uncoupling superimposed on changes of [K
+
]
e
and pH
e
contributed to the failure of impulse propagation between 19 and 30 minutes after the arrest of perfusion. During ischemia, maximum TQ-segment depression was −10 mV at 19 minutes, after which TQ-segment depression slowly recovered. The onset of the TQ-segment recovery was correlated to the second rise in R
t
(
R
2
=.886).

Conclusions
In the regionally ischemic in situ porcine heart, loss of cell-to-cell electrical interaction is related to the occurrence of VF and changes in the amplitude of the injury current. Cellular electrical uncoupling contributes to failure of impulse propagation in the setting of altered tissue excitability as a result of elevated [K
+
]
e
and low pH
e
. These data indicate that Ib arrhythmias and ECG changes during ischemia are influenced by the loss of cell-to-cell electrical interaction.