bluuebunny/crossref_metadata_2025 huggingface dataset:
New Look to an Old Symptom: Angina Pectoris
Authors: Crea Filippo , Gaspardone Achille
Published: June 2012

Abstract
At the turn of this century, it was proposed that ischemic cardiac pain might be related to distension of the ventricular wall (“mechanical hypothesis”). Three decades later, it was hypothesized that ischemic pain might be elicited by the intramyocardial release of pain-producing substances induced by ischemia (“chemical hypothesis”). Studies carried out in the past 10 years have given strong support to the chemical hypothesis, because they have consistently shown that adenosine is a mediator of ischemic cardiac pain. Adenosine-induced ischemic cardiac pain is mediated primarily by stimulation of A
1
receptors located in cardiac nerve endings and is potentiated by substance P. Conversely, the magnitude and rate of left ventricular dilation during ischemia do not predict the severity of angina. It is worth noting, however, that stretching of epicardial coronary arteries appears to potentiate the severity of angina caused by myocardial ischemia. The nervous activity generated by myocardial ischemia is modulated in intrinsic cardiac, mediastinal, and thoracic ganglia. Then it is further modulated in the central nervous system and projects bilaterally to the cortex, as demonstrated in humans by positron emission tomography, where it is decoded as a painful sensation. The causes responsible for the lack of angina during myocardial ischemia are probably different in patients who present both pain-free and painful myocardial ischemia, in patients with predominantly painless ischemia, and in diabetic patients.
Aortic Plaque Morphology and Vascular Events
Authors: Cohen Ariel , Tzourio Christophe , Bertrand Bernard , Chauvel Christophe , Bousser Marie-Germaine , Amarenco Pierre
Published: June 2012

Background
Atherosclerotic disease of the aortic arch has been found to be associated with the risk of ischemic stroke. We have shown that atherosclerotic plaques ≥4 mm in thickness in the ascending aorta and proximal arch detected by transesophageal echocardiography are a risk factor for ischemic stroke. The purpose of this study was to evaluate the impact, if any, of plaque morphology (ulceration, hypoechoic plaques or calcification) on the risk of subsequent vascular events.

Methods and Results
We followed for a period of 2 to 4 years, a cohort of 334 patients 60 years or older who were consecutively admitted with brain infarction and who had transesophageal echocardiography. The risk of vascular events in patients with plaques in the aortic arch according to the presence of surface ulceration, calcifications, and sessile or mobile thrombus was estimated during a total of 788 person-years of follow-up. Hypoechoic plaques, calcifications, and ulceration were more frequently found in patients with plaques ≥4 mm as compared with those with plaques <4 mm. The presence of ulceration did not increase the relative risk of vascular events in patients with plaque ≥4 mm (the relative risk was 4.3 [
P
<.001] in those with ulceration and 5.7 [
P
<.001]) in those without ulceration. The lack of calcification did increase the risk of vascular events in patients with plaque ≥4 mm. The highest relative risk of events was found among the patients with noncalcified plaques (relative risk, 10.3; 95% confidence interval, 4.2 to 25.2;
P
<.001). The risk of events was systematically higher in patients without calcifications than in patients with calcifications regardless of what other morphological features were considered.

Conclusions
In patients with brain infarction, the risk associated with aortic plaque thickness (≥4 mm) is markedly increased by the absence of plaque calcifications. These findings are important for the design of therapeutic trials in such patients.
Contemporary Percutaneous Treatment of Unprotected Left Main Coronary Stenoses
Authors: Ellis Stephen G. , Tamai Hideo , Nobuyoshi Masakiyo , Kosuga Kunihiko , Colombo Antonio , Holmes David R. , Macaya Carlos , Grines Cindy L. , Whitlow Patrick L. , White Harvey J. , Moses Jeffrey , Teirstein Paul S. , Serruys Patrick W. , Bittl John A. , Mooney Michael R. , Shimshak Thomas M. , Block Peter C. , Erbel Raimund
Published: June 2012

Background
Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG.

Methods and Results
To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15±8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (
P
=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (
P
<.001) and was inversely related to presentation with progressive or rest angina (
P
<.001). Surgical candidates with ejection fractions ≥40% had an in-hospital survival of 98% and a 9-month event-free survival of 86±5%, whereas patients with ejection fractions <40% had 67% and 22±12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge.

Conclusions
While results for selected patients appear promising, until early post–hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.
QT Dispersion Is Determined by the Extent of Viable Myocardium in Patients With Chronic Q-Wave Myocardial Infarction
Authors: Schneider Christian A. , Voth Eberhard , Baer Frank M. , Horst Michael , Wagner Rainer , Sechtem Udo
Published: June 2012

Background
QT dispersion is lower in patients with successful thrombolysis after acute myocardial infarction, suggesting that QT dispersion may be determined by the extent of viable and scarred myocardium.

Methods and Results
To test this hypothesis, QT dispersion was measured in a 12-lead resting ECG in 44 patients with chronic Q-wave myocardial infarction. To assess the extent of viable and scarred myocardium, all patients underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). In addition, all patients had revascularization of the infarct-related artery and repeated angiography 4 months later. QT dispersion was lower (53±20 versus 94±24 ms,
P
<.0001) in patients with evidence of a substantial amount of viable myocardium in the infarct region as demonstrated by PET (average FDG uptake ≥50% of normalized, maximum FDG uptake) than in patients with only minimal residual viability. Average FDG uptake of the infarct region and FDG defect size were significantly related to QT dispersion (
r
=.64,
P
<.0001;
r
=.67,
P
<.0001), whereas ejection fraction was not (
r
<.1,
P
=NS). QT dispersion of ≤70 ms had a sensitivity of 85% and a specificity of 82% to predict viable myocardium in the infarct region. QT dispersion was also lower in patients with improvement of left ventricular function 4 months after revascularization (54±21 versus 88±30 ms,
P
=.0003). QT dispersion of ≤70 ms had a sensitivity of 83% and a specificity of 71% to predict improvement of left ventricular function.

Conclusions
QT dispersion is determined by the amount of viable myocardium in the infarct region and may serve as a novel, rapidly available marker of substantial viability in the infarct region of patients with chronic Q-wave myocardial infarction.
Interventional Treatment for Children With Severe Coronary Artery Stenosis With Calcification After Long-term Kawasaki Disease
Authors: Sugimura Tetsu , Yokoi Hiroyoshi , Sato Noboru , Akagi Teiji , Kimura Takeshi , Iemura Motohumi , Nobuyoshi Masakiyo , Kato Hirohisa
Published: June 2012

Background
About 4% of children with Kawasaki disease (KD) eventually develop ischemic heart disease, which is often associated with calcified stenosis. We assessed the utility of the percutaneous transluminal coronary rotational ablation (PTCRA) in children with coronary artery stenosis after KD.

Methods and Results
Four children (three boys and one girl; age, 12 to 13 years) with coronary artery stenosis underwent percutaneous transluminal coronary angioplasty (PTCA) and PTCRA 11.8±0.9 years after the onset of KD. Morphology of the coronary artery wall was evaluated by intravascular ultrasound imaging. In one patient, the targeted lesion for intervention was in the left anterior descending artery (90% stenosis); in the other three patients, it was in the middle of the right coronary artery (75% to 90% stenosis). PTCA failed in three patients because of severe stenosis with calcification. However, PTCRA proved effective, with stenosis rates reduced from 90% to 25%. Follow-up coronary angiography performed 4 months after the procedure demonstrated no restenosis, but mild aneurysms occurred in two patients.

Conclusions
This study suggests that PTCRA is useful for revascularizing coronary arteries with severe stenosis and calcification as long-term sequelae of KD. Intravascular ultrasound imaging is useful in assessing the coronary artery wall pathology and in selecting the best treatment intervention.
Nitroglycerin Enhances the Ability of Dobutamine Stress Echocardiography to Detect Hibernating Myocardium
Authors: Ma Lijie , Chen Lianglong , Gillam Linda , Waters David D , Chen Chunguang
Published: June 2012

Background
A biphasic response of wall thickening with initial improvement and subsequent deterioration during dobutamine stress echocardiography (DSE) has been increasingly used for detection of hibernating myocardium. However, the improvement of wall thickening at low-dose DSE may be limited in hibernating myocardium by severe hypoperfusion. Nitroglycerin (NTG) improves myocardial perfusion, reduces oxygen demand, and may enhance low-dose dobutamine to improve wall thickening.

Methods and Results
A pig model of myocardial hibernation of 24 hours to 7 days was created through severe left anterior descending coronary artery stenosis with coronary flow reductions of ≈40%, producing severe regional left ventricular dysfunction but no infarction in seven pigs. Myocardial infarction was produced in five pigs with occlusion of the artery. DSE was performed with incremental doses with and without an NTG infusion of 50 to 100 μg/min. In the hibernating group, NTG alone improved wall thickening in the hibernating region modestly from 11.4±7.2% at baseline to 19.1±7.0%. The improvement was associated with increased regional coronary flow from 0.46±0.12 to 0.55±0.13 mL · beat
−1
· 100 g myocardium
−1
(
P
<.05). There was an additive effect of NTG to low-dose (2.5 to 5 μg · kg
−1
· min
−1
) dobutamine on wall thickening in the hibernating region. The improvement of wall thickening of hibernating myocardium with NTG and dobutamine, from 23.7±11.1% to 31.1±8.9% (
P
<.001), was associated with an increase in regional coronary flow (
P
<.01). NTG did not prevent high doses of dobutamine from inducing deterioration of wall thickening in hibernating myocardium. In the infarcted group, no improvement in wall thickening was observed in infarcted regions during NTG infusion, dobutamine infusion, or the combination.

Conclusions
NTG enhances the improvement of wall thickening at low-dose dobutamine and does not prevent high-dose dobutamine from inducing ischemia in hibernating myocardium. Thus, NTG augments the biphasic response of wall thickening and improves the accuracy of DSE for detecting viable myocardium.
Cholesterol-Lowering Therapy in Women and Elderly Patients With Myocardial Infarction or Angina Pectoris
Authors: Miettinen Tatu A. , Pyörälä Kalevi , Olsson Anders G. , Musliner Thomas A. , Cook Thomas J. , Faergeman Ole , Berg Kåre , Pedersen Terje , Kjekshus John , Group for the Scandinavian Simvastatin Study
Published: June 2012

Background
The Scandinavian Simvastatin Survival Study (4S) demonstrated pronounced reductions in mortality and major coronary events in a cohort of patients with established coronary heart disease (CHD). The present study provides a detailed, post hoc assessment of the efficacy and safety of simvastatin therapy in the following subgroups of 4S patients: those ≥65 years of age, those <65 years of age, women, and men.

Methods and Results
The 4S cohort of 4444 CHD patients included 827 women and 1021 patients ≥65 years of age. Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides ≤2.5 mmol/L. Patients were randomized to therapy with simvastatin 20 to 40 mg daily or placebo for a median follow-up period of 5.4 years. End points consisted of all-cause and CHD mortality, major coronary events (primarily CHD death and nonfatal myocardial infarction), other acute CHD and atherosclerotic events, hospitalizations for CHD and cardiovascular events, and coronary revascularization procedures. Mean changes in serum lipids were similar in the different subgroups. In patients ≥65 years of age in the simvastatin group, relative risks (95% confidence intervals) for clinical events were as follows: all-cause mortality, 0.66 (0.48 to 0.90); CHD mortality, 0.57 (0.39 to 0.83); major coronary events, 0.66 (0.52 to 0.84); any atherosclerosis-related event, 0.67 (0.56 to 0.81); and revascularization procedures, 0.59 (0.41 to 0.84). In women, the corresponding figures were 1.16 (0.68 to 1.99); 0.86 (0.42 to 1.74), 0.66 (0.48 to 0.91), 0.71 (0.56 to 0.91), and 0.51 (0.30 to 0.86), respectively.

Conclusions
Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (≥65 years of age) compared with younger patients. There were too few female deaths to assess the effects on mortality in women. Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients.
Summary Measures of the Insulin Resistance Syndrome Are Adverse Among Mexican-American Versus Non-Hispanic White Children
Authors: Batey Lyn Steffen , RD  , Goff David C. , Tortolero Susan R. , Nichaman Milton Z. , Chan Wenyaw , Chan Frances A. , Grunbaum JoAnne , EdD  , Hanis Craig L. , Labarthe Darwin R.
Published: June 2012

Background
Mexican-American (MA) adults are known to have a greater burden of diabetes and insulin resistance than non-Hispanic white (NHW) people. In this report, we examined data obtained from MA and NHW third-grade children for evidence of a pattern consistent with the insulin resistance syndrome. In addition, we developed two summary measures characterizing insulin resistance syndrome to compare measures of this syndrome among our population.

Methods and Results
Data regarding fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and body mass index (BMI) were available for 403 third-grade children. Median levels of insulin and glucose were significantly higher in MA boys and girls than in NHW boys and girls. Risk factors characterizing insulin resistance, including levels of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI were categorized as above or below the total population median. MA children were more likely than NHW children to have three or more adverse risk factors (55% versus 37%). When risk factors were converted to Z scores, and the five Z scores were summed for each individual, MA boys and girls had higher mean scores than NHW boys and girls (means for boys, 0.65 versus −0.97,
P
<.0001; girls, 0.52 versus −0.30,
P
<.04). Principal components analysis was used to create a summary score or index representing the insulin resistance syndrome. This summary score was significantly higher among MA boys and girls than NHW boys and girls (means for boys, 0.34 versus −0.72,
P
<.0001; girls, 0.35 versus −0.04,
P
=.056).

Conclusions
Our results support the hypothesis that MA children exhibit a greater degree of the insulin resistance syndrome than NHW children, especially among boys. We conclude that some of the factors responsible for the increased risk of NIDDM seen among MA adults are demonstrable in childhood.
Elevated
Chlamydia pneumoniae
Antibodies, Cardiovascular Events, and Azithromycin in Male Survivors of Myocardial Infarction
Authors: Gupta Sandeep , Leatham Edward W. , Carrington David , Mendall Michael A. , Kaski Juan Carlos , Camm A. John
Published: June 2012

Background
The clinical significance of the association between elevated anti–
Chlamydia pneumoniae
(Cp) antibody titres and coronary heart disease (CHD) is unclear. We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI). The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients.

Methods and Results
We screened 220 consecutive male survivors of MI for anti-Cp antibodies. Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at ≥1/64 dilution. Patients with persisting seropositivity of ≥1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or 500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial. The incidence of adverse cardiovascular events (over a mean follow-up period of 18±4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to 15.5;
P
=.03). In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6,
P
=NS). Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group (
P
=.02).

Conclusions
An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients. Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.
Attenuation of Compensation of Endogenous Cardiac Natriuretic Peptide System in Chronic Heart Failure
Authors: Tsutamoto Takayoshi , Wada Atsuyuki , Maeda Keiko , Hisanaga Tomoko , Maeda Yukiharu , Fukai Daisuke , Ohnishi Masato , Sugimoto Yoshihisa , Kinoshita Masahiko
Published: June 2012

Background
Patients with congestive heart failure (CHF) have high plasma levels of atrial natriuretic peptide (ANP), mainly from the atrium, and brain natriuretic peptide (BNP), mainly from the ventricle. We examined the prognostic role of plasma BNP in chronic CHF patients in comparison with plasma ANP and other variables previously known to be associated with high mortality. We also evaluated the relationship between mortality and plasma cGMP, a biological marker of ANP and BNP.

Methods and Results
The study subjects were 85 patients with chronic CHF (left ventricular ejection fraction <0.45) who were followed for 2 years. The plasma levels of ANP, BNP, cGMP, and norepinephrine increased with the severity of CHF. Among plasma levels of ANP, BNP, cGMP, and norepinephrine and clinical and hemodynamic parameters, only high levels of plasma BNP (
P
<.0001) and pulmonary capillary wedge pressure (
P
=.003) were significant independent predictors of the mortality in patients with CHF by Cox proportional hazard analysis. Although plasma levels of ANP and BNP were threefold or fivefold higher in nonsurvivors than in survivors, there was no difference in plasma cGMP level between nonsurvivors and survivors.

Conclusions
These findings indicate that plasma BNP is more useful than ANP for assessing the mortality in patients with chronic CHF and that the plasma levels of BNP provide prognostic information independent of other variables previously associated with a poor prognosis. Our findings also suggest that the compensatory activity of the cardiac natriuretic peptide system is attenuated as mortality increases in chronic CHF patients with high plasma levels of ANP and BNP.
Effects of Thyroid Hormone on Cardiac β-Adrenergic Responsiveness in Conscious Baboons
Authors: Hoit Brian D. , Khoury Saeb F. , Shao Yanfu , Gabel Marjorie , Liggett Stephen B. , Walsh Richard A.
Published: June 2012

Background
Many of the cardiovascular manifestations of thyroid hormone excess resemble those produced by sympathoadrenal stimulation. The objective of this study was to determine the effects of thyroid hormone excess on myocardial β-adrenergic expression and responsiveness to infused agonists in the primate heart.

Methods and Results
The responses of left ventricular isovolumic contraction (dP/dt
max
) and relaxation (τ) during graded dobutamine infusion were studied both before and after 4 weeks of thyroid hormone administration in 8 chronically instrumented baboons. At matched (atrially paced) heart rates, thyroid hormone significantly increased resting dP/dt
max
(3073±1034 versus 2318±829 mm Hg/s,
P
<.05) and decreased τ (24.0±5.5 versus 28.2±5.4 ms,
P
<.05). The change from baseline for dP/dt
max
and τ in response to β
1
-adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 μg·kg
−1
·min
−1
), but when expressed as a percent change, it was similar before versus after thyroid hormone. Similar changes were found when β
2
-adrenergic stimulation was produced by terbutaline infusion in three additional baboons. β-Adrenergic receptor (βAR) expression was higher in five thyroxine-treated than in five control baboons (37.4±1.2 versus 15.7±3.2 fmol/mg,
P
<.001), and this was due to a greater increase in the β
2
AR (5.9±1.5 to 20.6±1.2 fmol/mg,
P
<.001) than the β
1
AR (9.7±1.7 to 16.8±0.1 fmol/mg,
P
<.01) subtype.

Conclusions
In the primate heart, thyroid hormone produces positive inotropic and lusitropic effects in the resting state and upregulates both β
1
AR and β
2
AR, with the β
2
AR increase predominating. At equivalent rates, however, thyroid hormone excess does not appear to enhance the sensitivity of left ventricular contractility and relaxation to either β
1
- or β
2
-adrenergic stimulation.
Noninvasive Electrocardiographic Imaging
Authors: Oster Howard S. , Taccardi Bruno , Lux Robert L. , Ershler Philip R. , Rudy Yoram
Published: June 2012

Background
The goal of noninvasive electrocardiographic imaging (ECGI) is to determine electric activity of the heart by reconstructing maps of epicardial potentials, excitation times (isochrones), and electrograms from data measured on the body surface.

Methods and Results
Local electrocardiac events were initiated by pacing a dog heart in a human torso–shaped tank. Body surface potential measurements (384 electrodes) were used to compute epicardial potentials noninvasively. The accuracy of reconstructed epicardial potentials was evaluated by direct comparison to measured ones (134 electrodes). Protocols included pacing from single sites and simultaneously from two sites with various intersite distances. Body surface potentials showed a single minimum for both single- and double-site pacing (intersite distances of 52, 35, and 17 mm). Noninvasively reconstructed epicardial electrograms, potentials, and iso-chrones closely approximated the measured ones. Single pacing sites were reconstructed to within ≤10 mm of their measured positions. Dual sites were located accurately and resolved for the above intersite distances. Regions of sparse and crowded isochrones, indicating spatial nonuniformities of epicardial activation spread, were also reconstructed.

Conclusions
The study demonstrates that ECGI can reconstruct epicardial potentials, electrograms, and isochrones over the entire epicardial surface during the cardiac cycle. It can provide detailed information on local activation of the heart noninvasively. Its uses could include localization of cardiac electric events (eg, ectopic foci), characterization of nonuniformities of conduction, characterization of repolarization properties (eg, dispersion), and mapping of dynamically changing arrhythmias (eg, polymorphic VT) on a beat-by-beat basis.
Long-term Angiographic and Clinical Outcome After Percutaneous Transluminal Coronary Angioplasty and Intracoronary Radiation Therapy in Humans
Authors: Condado Jose A. , Waksman Ron , Gurdiel Orlando , Espinosa Raul , Gonzalez Juan , Burger Bruno , Villoria Guillermo , Acquatella Harry , Crocker Ian R. , Seung K. B. , Liprie Samuel F.
Published: June 2012

Background
Ionizing radiation has been shown to reduce neointimal formation after balloon angioplasty in experimental models of restenosis. This study was designed to evaluate the feasibility, safety, and effectiveness of intracoronary radiation therapy (ICRT) after percutaneous transluminal coronary angioplasty (PTCA) for preventing restenosis in human coronary arteries.

Methods and Results
Twenty-one patients (22 arteries) with unstable angina underwent standard balloon angioplasty. ICRT was performed with the use of an
192
Ir source wire that was hand delivered to the angioplasty site. Angiographic follow-up was performed at 24 hours, between 30 and 60 days, and at 6 months. Angioplasty was successful in 19 of 22 lesions, and insertion of the radioactive source wire was successful at all treated sites. Angiographic study at 24 hours demonstrated early late loss of the luminal diameter from 1.92±0.55 to 1.40±0.27 mm. Between 30 and 60 days, repeat angiography demonstrated total occlusion in 2 arteries, a new pseudoaneurysm in 1 artery, and significant dilatation at the treatment site in 2 additional vessels. At ≥6 months’ follow-up, all remaining arteries (n=20) maintained patent, with a mean lumen diameter of 1.65±0.8 mm. The calculated late lumen loss was 0.27±0.56 mm, and the late loss index was 0.19. Clinical events at 1 year included myocardial infarction in 1 patient, repeat angioplasty to the treated site in 3 patients, and persistent angina in 7 patients.

Conclusions
These preliminary results demonstrate that ICRT after coronary intervention is feasible and is associated with an acceptable degree of complications and lower rates of angiographic restenosis indexes.
Improved Outcome After Coronary Bypass Surgery in Patients With Ischemic Cardiomyopathy and Residual Myocardial Viability
Authors: Pagley Paul R. , Beller George A. , Watson Denny D. , Gimple Lawrence W. , Ragosta Michael
Published: June 2012

Background
Although residual myocardial viability in patients with coronary artery disease and extensive regional asynergy is associated with improved ventricular function after coronary bypass surgery, the relationship between viability and clinical outcome after surgery is unclear. We hypothesized that patients with poor ventricular function and predominantly viable myocardium have a better outcome after bypass surgery compared with those with less viability.

Methods and Results
Seventy patients with multivessel coronary artery disease and left ventricular ejection fractions <40% who underwent preoperative quantitative
201
Tl scintigraphy before coronary bypass surgery were analyzed retrospectively.
201
Tl scintigrams were reviewed blindly, and each segment was assigned a score based on defect magnitude. Segmental viability scores were summed and divided by the number of segments visualized to determine a viability index. The viability index was significantly related to 3-year survival free of cardiac event (cardiac death or heart transplant) after bypass surgery (
P
=.011) and was independent of age, ejection fraction, and number of diseased coronary vessels. Patients with greater viability (group 1; viability index >0.67; n=33) were similar to patients with less viability (group 2; viability index ≤0.67; n=37) with respect to age, comorbidities, and extent of coronary artery disease. There were 6 cardiac deaths and no heart transplants in group 1 patients and 15 cardiac deaths and two transplants in group 2 patients. Survival free of cardiac death or transplantation was significantly better in group 1 patients on Kaplan-Meier analysis (
P
=.018).

Conclusions
We conclude that resting
201
Tl scintigraphy may be useful in preoperative risk stratification for identification of patients more likely to benefit from surgical revascularization.
Dynamics of Left Ventricular Apex Rotation During Angioplasty
Authors: Knudtson Merril L. , Galbraith P. Diane , Hildebrand Kathy L. , Tyberg John V. , Beyar Rafael
Published: June 2012

Background
Apex rotation has been shown to provide a reliable index of the dynamics of left ventricular (LV) twist. In this study, we aimed to characterize twist at baseline and during acute ischemia in 20 patients undergoing percutaneous transluminal coronary angioplasty to the left anterior descending (LAD) artery and to test whether an old myocardial infarction or collateral flow affected twist dynamics.

Methods and Results
Among patients with no previous infarction, five had no collaterals (group A) and six had angiographically visible collaterals (group B). Previous anterior infarction was present in nine patients (group C). Data were acquired with the LAD angioplasty wire passed beyond the apex using a view aligned with the LV long axis. Frame-by-frame dynamics of apex rotation were measured from the angular movement of the portion of the wire that traversed the apex. Aortic pressure recordings allowed precise temporal definition of the cardiac cycle. Dynamics of apex rotation were measured at fixed intervals until 60 seconds of occlusion and up to 60 seconds of reperfusion. In group A, counterclockwise apex rotation (twist) during ejection of −22.0±1.7° (mean±SEE) was followed by rapid clockwise rotation (untwist) during isovolumic relaxation. During 60 seconds of ischemia, maximum apex rotation decreased to −8.2±2.0° (
P
<.001 versus baseline). In group B, baseline apex rotation was similar (−26.2±6.9°) to that in group A, but ischemia had less effect, with apex rotation values of −17.7±3.4° (
P
<.05 versus group A values). Group C was characterized by reduced baseline apex rotation values (−9.7±3.1°,
P
<.05 versus group A values), with little change observed during ischemia (−8.1±2.6°).

Conclusions
Apex rotation, an index of ventricular twist, is sensitive to acute ischemia in patients without previous myocardial infarction. Visible collaterals to the ischemic region attenuate the acute ischemic response at 60 seconds. Previous myocardial infarction causes abnormalities in the baseline twist pattern with no further deterioration at 60 seconds of ischemia.
Abnormal Cardiac Adrenergic Nerve Function in Patients With Syndrome X Detected By [
123
I]Metaiodobenzylguanidine Myocardial Scintigraphy
Authors: Lanza Gaetano Antonio , Giordano Alessandro , Pristipino Christian , Calcagni Maria Lucia , Meduri Guido , Trani Carlo , Franceschini Rodolfo , Crea Filippo , Troncone Luigi , Maseri Attilio
Published: June 2012

Background
Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries).

Methods and Results
To evaluate cardiac adrenergic nerve function, we performed [
123
I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by
201
Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (
P
<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70±0.6 versus 2.2±0.3,
P
=.03) and MIBG uptake defect score higher (35±31 versus 4±2,
P
=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5±3-month follow-up study.

Conclusions
In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.
Clinical Significance of Mitral Regurgitation After Acute Myocardial Infarction
Authors: Lamas Gervasio A. , Mitchell Gary F. , Flaker Greg C. , Smith Sidney C. , Gersh Bernard J. , Basta Lofty , Moyé Lemuel , Braunwald Eugene , Pfeffer Marc A.
Published: June 2012

Background
Mitral regurgitation (MR) may complicate acute myocardial infarction (MI). However, it is not known whether mild MR is an independent predictor of post-MI outcome.

Methods and Results
The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization, including left ventriculography, up to 16 days after MI. Left ventriculograms were analyzed for diastolic and systolic volumes, global left ventricular sphericity, extent of wall motion abnormality, and endocardial curvature. The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe (3+) MR was present in only 2 patients. Patients with MR were more likely to have a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%;
P
=.001). Although the ejection fractions were similar, MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR. Sphericity change from diastole to systole was also significantly reduced in MR patients. Patients with MR were more likely to experience cardiovascular mortality (29% versus 12%;
P
<.001), severe heart failure (24% versus 16%;
P
=.0153), and the combined end point of cardiovascular mortality, severe heart failure, or recurrent myocardial infarction (47% versus 29%;
P
<.001). The presence of MR was an independent predictor of cardiovascular mortality (relative risk, 2.00; 95% CI, 1.28 to 3.04).

Conclusions
Mild MR is an independent predictor of post-MI mortality. As such, it adds important information for risk stratification of post-MI patients.
Predicting Survival in Heart Failure Case and Control Subjects by Use of Fully Automated Methods for Deriving Nonlinear and Conventional Indices of Heart Rate Dynamics
Authors: Ho Kalon K. L. , Moody George B. , Peng Chung-Kang , Mietus Joseph E. , Larson Martin G. , Levy Daniel , Goldberger Ary L.
Published: June 2012

Background
Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted.

Methods and Results
We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7±8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (
P
<.01), LF (
P
<.01), VLF (
P
<.05), and TP (
P
<.01) and the nonlinear measure DFA (
P
<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (
P
>.3), were not. In multivariable models, DFA was of borderline predictive significance (
P
=.06) after adjustment for the diagnosis of CHF and SD.

Conclusions
These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.
Effect of the Calcium Antagonist Felodipine as Supplementary Vasodilator Therapy in Patients With Chronic Heart Failure Treated With Enalapril
Authors: Cohn Jay N. , Ziesche Susan , Smith Raphael , Anand Inder , Dunkman W. Bruce , Loeb Henry , Cintron Guillermo , Boden William , Baruch Lawrence , Rochin Peter , Loss Larrye
Published: June 2012

Background
Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator.

Methods and Results
Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus −0.1% units in the placebo group,
P
=.001) and reduced plasma atrial natriuretic peptide levels (−2.9 versus 26.9 pg/mL in the placebo group,
P
=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy.

Conclusions
Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.
Association of Cigarette Smoking With Chronotropic Incompetence and Prognosis in the Framingham Heart Study
Authors: Lauer Michael S. , Pashkow Fredric J. , Larson Martin G. , Levy Daniel
Published: June 2012

Background
In this study, we sought to determine whether cigarette smoking is associated with chronotropic incompetence and to explore prognostic implications of this association.

Methods and Results
Members of the Framingham Offspring Study (1468 men and 1642 women) underwent graded exercise. Chronotropic incompetence was assessed in two ways: (1) failure to achieve an age-predicted target heart rate and (2) a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness. Smokers were more likely to fail to reach target heart rate than were nonsmokers (men, 25% versus 15%, odds ratio [OR], 1.97; 95% confidence interval [CI], 1.51 to 2.56; women, 32% versus 18%; OR, 2.10; 95% CI, 1.63 to 2.61) and were more likely to have a low chronotropic index (men, 17% versus 12%; OR, 1.50; 95% CI, 1.12 to 2.03; women, 17% versus 8%; OR, 2.28; 95% CI, 1.68 to 3.09). These associations persisted after adjustment for age, cardiovascular risk factors, pulmonary function, and ST-segment response to graded exercise. During 8 years of follow-up, there were 48 deaths and 90 incident coronary heart disease events among the men. After adjustment for the same confounders, men who were smokers and failed to achieve target heart rate were at particularly high risk for death (adjusted relative risk [RR], 2.45; 95% CI, 1.14 to 5.24) and for coronary heart disease (adjusted RR, 4.92; 95% CI, 2.84 to 8.53). There were too few end points in women for analysis.

Conclusions
In this population-based cohort, cigarette smoking was predictive of chronotropic incompetence. Male smokers who manifested chronotropic incompetence were at particularly high risk for death and coronary heart disease events.
Arterial Remodeling After Balloon Angioplasty or Stenting in an Atherosclerotic Experimental Model
Authors: Post Mark J. , de Smet Bart J. G. L. , van der Helm Yvonne , Borst Cornelius , Kuntz Richard E.
Published: June 2012

Background
Recent studies have indicated that coronary restenosis after balloon angioplasty is the sum of geometric remodeling and neointimal formation. A proportional relationship between acute gain and late lumen loss has been observed in clinical trials. The aims of this study were to evaluate (1) the contribution of geometric remodeling and neointimal formation to the proportional gain-loss relationship after PTA or stenting and (2) the relationship between geometric remodeling and neointimal formation.

Methods and Results
In atherosclerotic iliac arteries of 29 Yucatan micropigs, PTA or stenting was performed, with serial intravascular ultrasound (IVUS) and quantitative angiography before and after intervention and at 2 or 42 days of follow-up, followed by histomorphometrical analysis. For PTA at 42 days, late lumen loss by IVUS correlated strongly with geometric remodeling, expressed as late media-bounded area (MBA) loss (
R
2
=.843,
P
<.001, n=20), and correlated weakly with intimal hyperplasia area (
R
2
=.214,
P
=.02). For stented arteries, however, late lumen loss correlated moderately with intimal hyperplasia (
R
2
=.367,
P
=.01, n=18) and only weakly with geometric remodeling (
R
2
=.195,
P
=.04). Late lumen loss and late MBA loss of reference segments were observed at 42 days, especially in PTA arteries. Intimal hyperplasia and geometric remodeling were not correlated.

Conclusions
In this experimental model, the proportional relationship between acute gain and late lumen loss is mainly due to the proportional relationship between acute gain and geometric remodeling for PTA and between acute gain and intimal hyperplasia for stents. Finally, neointimal formation and remodeling seem to be unrelated processes.
Differential Suppression of Thromboxane Biosynthesis by Indobufen and Aspirin in Patients With Unstable Angina
Authors: Cipollone Francesco , Patrignani Paola , Greco Anita , Panara Maria Rosaria , Padovano Roberto , Cuccurullo Franco , Patrono Carlo , Rebuzzi Antonio G. , Liuzzo Giovanna , Quaranta Gaetano , Maseri Attilio
Published: June 2012

Background
We have previously reported aspirin failure in suppressing enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation during the acute phase of unstable angina. The recent discovery of a second prostaglandin H synthase (PGHS-2), inducible in response to inflammatory or mitogenic stimuli, prompted us to reexamine TXA
2
biosynthesis in unstable angina as modified by two cyclooxygenase inhibitors differentially affecting PGHS-2 despite a comparable impact on platelet PGHS-1.

Methods and Results
We randomized 20 patients (15 men and 5 women aged 59±10 years) with unstable angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID) and collected 6 to 18 consecutive urine samples. Urinary 11-dehydro-TXB
2
was extracted and measured by a previously validated radioimmunoassay as a reflection of in vivo TXA
2
biosynthesis. Metabolite excretion averaged 102 pg/mg creatinine (median value; n=76) in the aspirin group and 55 pg/mg creatinine (median value; n=99) in the indobufen group (
P
<.001). There were 16 samples (21%) with 11-dehydro-TXB
2
excretion >200 pg/mg creatinine among patients treated with aspirin versus 6 such samples (6%) among those treated with indobufen (
P
<.001). In vitro and ex vivo studies in healthy subjects demonstrated the capacity of indobufen to largely suppress monocyte PGHS-2 activity at therapeutic plasma concentrations. In contrast, aspirin could only inhibit monocyte PGHS-2 transiently at very high concentrations.

Conclusions
We conclude that in unstable angina, episodes of aspirin-insensitive TXA
2
biosynthesis may reflect extraplatelet sources, possibly expressing the inducible PGHS in response to a local inflammatory milieu, and a selective PGHS-2 inhibitor would be an ideal tool to test the clinical relevance of this novel pathway of arachidonic acid metabolism in this setting.
Profound and Sustained Inhibition of Platelet Aggregation by Fradafiban, a Nonpeptide Platelet Glycoprotein IIb/IIIa Antagonist, and Its Orally Active Prodrug, Lefradafiban, in Men
Authors: Müller Thomas H. , Weisenberger Hans , Brickl Rolf , Narjes Hans , Himmelsbach Frank , Krause Jürgen
Published: June 2012

Background
Clinical trials have demonstrated that platelet glycoprotein (GP) IIb/IIIa antagonists effectively prevent acute thrombotic events. Orally active GP IIb/IIIa antagonists are essential to evaluate the clinical benefit of long-term treatment. We therefore investigated platelet inhibition by the GP IIb/IIIa antagonist Fradafiban (BIBU 52; Fradafiban is the recommended INN of BIBU 52) and its orally administered prodrug, Lefradafiban (BIBU 104; Lefradafiban is the recommended INN of BIBU 104) in healthy subjects.

Methods and Results
The activity and plasma levels of Fradafiban and Lefradafiban were evaluated in double-blind, placebo-controlled studies in 130 healthy male subjects. One to 15 mg Fradafiban continuously infused over 30 minutes reversibly inhibited platelet aggregation in platelet-rich plasma ex vivo in response to 20 μmol/L ADP (5 mg, 100% inhibition at 27 minutes after administration) and to both 1.0 (5 mg, 100%) and 10 μg/mL (15 mg, 97±3%) collagen. Single oral doses of Lefradafiban inhibited ADP-induced aggregation by 59±14% (50 mg [mean±SD]; n=8), 90±12% (100 mg), and 99±2% (150 mg) 8 hours after administration. Correlations between activity and Fradafiban plasma levels were identical after Fradafiban and Lefradafiban treatment. After day 1, oral TID Lefradafiban treatment for 7 days inhibited aggregation by ≥31±9.6% (25 mg TID; n=8), 53±12% (50 mg; n=7), and 88±6.6% (75 mg; n=8) just before the next dose. A similar correlation between the activity and Fradafiban plasma levels was observed at days 1, 2, and 7.

Conclusions
Oral administration of Lefradafiban maintains the potent platelet GP IIb/IIIa antagonism of Fradafiban during treatment of healthy subjects for 1 week without signs of loss of the antiplatelet activity.