bluuebunny/crossref_metadata_2025 huggingface dataset:
Fat-suppressed breath-hold magnetic resonance coronary angiography.
Authors: Manning W J , Li W , Boyle N G , Edelman R R
Published: June 2012

BACKGROUND

The ability to image the coronary arteries noninvasively would represent an advance in patient care. We have developed a magnetic resonance (MR) angiographic technique that allows the acquisition of complete images of coronary flow within a single breath-hold. By this method, the feasibility of noninvasive MR coronary angiography was evaluated in 25 subjects, including 19 healthy adult volunteers and six patients after diagnostic coronary angiography.

METHODS AND RESULTS

Noninvasive MR coronary angiography was performed with a fat-suppressed ECG-gated gradient-echo sequence with k-space segmentation. Overlapping transverse sections were initially used to image coronary flow, with oblique images obtained after identification of proximal anatomy. The left main coronary artery was seen in 24 subjects (96%), with a mean diameter of 4.8 mm (range, 3.4-6.2 mm) and average length of 10 mm (range, 8-14 mm). The left anterior descending coronary artery was seen in 100% of subjects, with a mean proximal diameter of 3.6 mm (range, 2.6-4.3 mm) and for an average length of 44 mm (range, 28-93 mm). The left circumflex coronary artery was seen in 76% of subjects, with a mean proximal diameter of 3.5 mm (range, 2.6-4.3 mm) and for an average length of 25 mm (range, 9-42 mm). The right coronary artery was also identified in 100% of subjects, with a mean proximal diameter of 3.7 mm (range, 2.7-5.1 mm) and for an average length of 58 mm (range, 24-122 mm). Quantitative angiography of normal proximal segments demonstrated a good correlation with MR-determined lumen diameters (r = 0.86, p < 0.002). Occluded vessels in patients with coronary artery disease displayed an absence of flow signal distal to the occlusion, whereas vessels with significant angiographic stenoses demonstrated signal loss corresponding to the area of the stenosis, with visualization of the more distal vessel.

CONCLUSIONS

Breath-hold MR coronary angiography provides visualization of the major epicardial vessels. In the future, MR coronary angiography may provide a noninvasive means for the evaluation of patients with known or suspected coronary artery disease.
Time course of functional improvement in stunned myocardium in risk area in patients with reperfused anterior infarction.
Authors: Ito H , Tomooka T , Sakai N , Higashino Y , Fujii K , Katoh O , Masuyama T , Kitabatake A , Minamino T
Published: June 2012

BACKGROUND

The beneficial effect of coronary reflow on myocardial salvage may be assessed more accurately than in previous studies if the size of risk area is taken into account, particularly because the size of risk area varies significantly among patients. In this study, the risk area was determined with myocardial contrast echocardiography to investigate the time course of functional recovery of postischemic myocardium within the risk area in patients with reperfused anterior myocardial infarction.

METHODS AND RESULTS

The study population consisted of 21 patients with anterior myocardial infarction who achieved coronary reflow within 6 hours of onset by means of thrombolysis or coronary angioplasty. Myocardial contrast echocardiography was performed with the injection of hand-agitated Haemaccel (5 ml) into the right and left coronary arteries before coronary reflow, and the risk area was defined as the area of contrast perfusion defect in the apical long-axis view. The ratio of the endocardial length of abnormal contraction (dyskinesis/akinesis) segment to that of contrast defect segment (AS/CD) was determined at days 1, 2, 3, 7, 14, and 28 of reflow. Before reflow, the length of contrast defect correlated well with the segment length of dyskinesis/akinesis. The values for AS/CD in patients with successful reperfusion significantly and progressively decreased until day 14; 1.00 +/- 0.02 at day 1, 0.93 +/- 0.11 at day 2 (p < 0.05 versus day 1), 0.84 +/- 0.16 at day 3 (p < 0.05 versus day 2), 0.80 +/- 0.13 at day 7 (p < 0.01 versus day 2), 0.73 +/- 0.10 at day 14, and 0.72 +/- 0.10 at day 28. Greater improvement in function was obtained in patients reperfused within 4 hours than in those reperfused at > or = 4 hours (AS/CD at day 28, 0.64 +/- 0.12 versus 0.75 +/- 0.09, p < 0.05).

CONCLUSIONS

Thus, a significant amount of myocardium, an average of 28% in segment length of the risk area, is salvaged in patients with reperfused anterior myocardial infarction. Major functional improvement seems to be achieved within 14 days of reflow.
Chronic changes in skeletal muscle histology and function in peripheral arterial disease.
Authors: Regensteiner J G , Wolfel E E , Brass E P , Carry M R , Ringel S P , Hargarten M E , Stamm E R , Hiatt W R
Published: June 2012

BACKGROUND

Peripheral arterial disease (PAD) is associated with an impairment in exercise performance and muscle function that is not fully explained by the reduced leg blood flow during exercise. This study characterized the effects of PAD on muscle function, histology, and metabolism.

METHODS AND RESULTS

Twenty-six patients with PAD and six age-matched control subjects were studied. Ten of the PAD patients had unilateral disease, which permitted paired comparisons between their diseased and nonsymptomatic legs. All PAD patients had a lower peak treadmill walking time and peak oxygen consumption than controls. Vascular disease (diseased leg in unilateral patients and the most severely diseased leg in bilateral patients) was associated with decreased calf muscle strength compared with control values. In patients with unilateral disease, the diseased legs had a greater percentage of angular fibers (indicating chronic denervation) and a decreased type II fiber cross-sectional area (expressed as percent of total fiber area) compared with the nonsymptomatic, or control, legs. In diseased legs, gastrocnemius muscle strength was correlated with the total calf cross-sectional area (r = 0.78, p < 0.05) and type II fiber cross-sectional area (r = 0.63, p < 0.05). Activities of citrate synthase, phosphofructokinase, and lactate dehydrogenase in all 26 PAD patients (most diseased leg) did not differ from control values. Despite a wide range in citrate synthase activity in PAD patients, activity of this enzyme was not correlated with muscle strength or treadmill exercise performance.

CONCLUSIONS

In patients with PAD, gastrocnemius muscle weakness is associated with muscle fiber denervation and a decreased type II fiber cross-sectional area. In contrast, the PAD patients displayed substantial heterogeneity in muscle enzyme activities that was not associated with exercise performance. Denervation and type II fiber atrophy may contribute to the muscle dysfunction in patients with PAD and further confirm that the pathophysiology of chronic PAD extends beyond arterial obstruction.
Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics.
Authors: Celermajer D S , Cullen S , Deanfield J E
Published: June 2012

BACKGROUND

Endothelial injury may be an important event in the pathophysiology of pulmonary hypertension. We therefore investigated whether endothelial dysfunction occurs early in children with congenital heart defects who are at risk of developing pulmonary vascular disease.

METHODS AND RESULTS

In 25 children aged 3-16 years, we studied the response of the pulmonary circulation to graded infusions of acetylcholine (an endothelium-dependent vasodilator) and nitroprusside (a dilator not dependent on endothelial function). Diameter of a bronchopulmonary segment artery and pulmonary blood flow velocity were measured using quantitative angiography and intra-arterial Doppler catheters in 10 children aged 4-16 years with normal pulmonary hemodynamics (controls), seven children aged 3-12 years with left-to-right shunt lesions resulting in increased pulmonary flow, and eight children aged 3-14 years with established pulmonary vascular disease. In the controls, there was a dose-dependent increase in flow velocity in response to acetylcholine (maximal increase, 93 +/- 7%) and in response to nitroprusside (51 +/- 8%). In contrast, in patients with pulmonary vascular disease, the response of flow velocity to similar doses of acetylcholine (33 +/- 7%, p < 0.01) and nitroprusside (7 +/- 13%, p < 0.01) were impaired. In the patients with high pulmonary flow, there was an impaired response to acetylcholine (46 +/- 9%, p < 0.01), but response to nitroprusside was preserved (42 +/- 8%, p > 0.10), consistent with endothelial dysfunction. Arterial diameter was unchanged during acetylcholine infusion in all subjects and increased only modestly in response to nitroprusside (< or = 10%), indicating that the major site of action of each agent is distal to the segmental pulmonary arteries.

CONCLUSIONS

Endothelium-dependent pulmonary artery relaxation can be demonstrated in vivo and is impaired in young patients with increased pulmonary flow secondary to congenital heart disease. This impairment may be an important early event in the pathogenesis of pulmonary vascular disease.
Comparative study on the proarrhythmic effects of some antiarrhythmic agents.
Authors: Dhein S , Müller A , Gerwin R , Klaus W
Published: June 2012

BACKGROUND

A main side effect of antiarrhythmic drug therapy is the tendency of these drugs to promote arrhythmia within the therapeutic concentration range, i.e., the proarrhythmic activity of these drugs. However, a model for in vitro assessment, quantification, and comparison of proarrhythmic drug activities was still lacking, and only sparse data were available.

METHODS AND RESULTS

To analyze the arrhythmogenic risk of common antiarrhythmic drugs in a quantitative and comparative manner, isolated perfused rabbit hearts were treated with increasing concentrations of antiarrhythmic drugs corresponding to low, medium, and high therapeutic concentrations. For analysis of the epicardial activation process, an epicardial mapping (256 unipolar leads) was performed. For each electrode, the activation time was determined. From these data, the origins of epicardial activation ("breakthrough points" [BTP]) were determined. At each electrode, an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heartbeats (under treatment) compared with control was evaluated by determination of the percentage of identical BTPs (deviation < or = 1 mm) and of similar VECs (deviation < or = 5 degrees). BTP and VEC were reduced by all antiarrhythmic agents tested (propafenone = flecainide > quinidine > ajmaline > procainamide > disopyramide > mexiletine = lidocaine > sotalol), indicating a more or less pronounced disturbance of the epicardial activation process. Treatment with propafenone, quinidine, and disopyramide and to a lesser extent sotalol prolonged the activation-recovery interval (ARI). ARI dispersion was greatly enhanced by flecainide and was reduced by sotalol. In addition, it could be shown that propranolol is able to reduce the proarrhythmic action of flecainide. This effect seemed to be due to a reduction of the flecainide-induced increase in ARI dispersion.

CONCLUSIONS

From the results of our study, we propose the following rank order of the arrhythmogenic risk: flecainide > propafenone > quinidine > ajmaline > disopyramide > procainamide > mexiletine, lidocaine > sotalol. Moreover, we conclude that propranolol given additionally may be helpful in reducing the proarrhythmic risk of flecainide.
Epidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study.
Authors: Manolio T A , Ettinger W H , Tracy R P , Kuller L H , Borhani N O , Lynch J C , Fried L P
Published: June 2012

BACKGROUND

Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths.

METHODS AND RESULTS

This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels < or = 160 mg/dL were present in 11.6% of men and 3.7% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes.

CONCLUSIONS

Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies.
Hemodynamic characteristics of the early phase of primary hypertension. The Dutch Hypertension and Offspring Study.
Authors: van Hooft I M , Grobbee D E , Waal-Manning H J , Hofman A
Published: June 2012

BACKGROUND

The hemodynamic characteristics of the early phase of primary hypertension are subject to debate. In particular, it remains unclear whether an increased vascular peripheral resistance or a raised cardiac output is involved as the primary hemodynamic alteration in hypertension.

METHODS AND RESULTS

We studied hemodynamic characteristics and oxygen consumption in relation to 24-hour ambulatory blood pressure measurements in three groups of normotensive children with a different familial predisposition for hypertension. Selection of participants was based on parental blood pressure levels. Mean 24-hour blood pressure was higher in the offspring of two hypertensive parents compared with the offspring of two normotensive parents; there was a difference of 4.7 mm Hg (95% confidence interval [CI], 1.8-7.6) for systolic blood pressure and a difference of 4.8 mm Hg (CI, 2.3-7.3) for diastolic blood pressure. The 24-hour blood pressure pattern was consistently at a higher level for both systolic and diastolic blood pressures in the offspring of two hypertensive parents compared with the offspring of two normotensive parents. The smallest differences in blood pressure were seen at night, and the largest differences in blood pressure between the groups of offspring were seen during periods of physical activity. Echocardiographic examination combined with registration of oxygen consumption did not show a difference in cardiac index and arteriovenous oxygen difference between the study groups. However, differences in cardiac dimensions were apparent, with an increased left ventricular mass index (8.7 g/m2; CI, 2.4-15.0) in the offspring of two hypertensive parents.

CONCLUSIONS

These findings do not support the existence of a hyperkinetic circulatory phase but may indicate the presence of an increased left ventricular mass in early primary hypertension.
Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults. The Atherosclerosis Risk in Communities Study.
Authors: Malinow M R , Nieto F J , Szklo M , Chambless L E , Bond G
Published: June 2012

BACKGROUND

Plasma levels of homocyst(e)ine are elevated in certain patients with occlusive arterial diseases. We extended these findings to asymptomatic adults.

METHODS AND RESULTS

We determined plasma homocyst(e)ine levels in 287 pairs of asymptomatic adults. Cases and controls were defined on the basis of intimal-medial thickness of the carotid wall as measured by B-mode ultrasound. Study subjects had no history of atherosclerotic disease and were selected from a probability sample of 15,800 men and women between 45 and 64 years old. Subjects with thickened intimal-medial carotid walls (cases) had higher plasma homocyst(e)ine levels than controls (p < 0.001). The odds ratio for having a thickened carotid artery wall was 3.15 (p < 0.001) for subjects in the top quintile of plasma homocyst(e)ine levels (> 10.5 mumol/L) compared with those in the bottom quintile (< 5.88 mumol/L).

CONCLUSIONS

The present study as well as observations on the common occurrence of elevated plasma homocyst(e)ine levels in patients with occlusive arterial diseases suggest that clinical trials should be conducted to determine whether normalization of hyperhomocyst(e)inemia may prevent progression of atherosclerosis.
Lesion-to-lesion independence of restenosis after treatment by conventional angioplasty, stenting, or directional atherectomy. Validation of lesion-based restenosis analysis.
Authors: Gibson C M , Kuntz R E , Nobuyoshi M , Rosner B , Baim D S
Published: June 2012

BACKGROUND

Since many restenosis trials include patients in whom more than one lesion is treated, analysis of the angiographic data on a "per lesion" basis might be confounded by potential correlations of restenosis among multiple treated lesions within each patient. The goals of this study were: 1) to determine whether there was any correlation in the rate of restenosis among multiple lesions that underwent conventional angioplasty, stenting, or directional atherectomy within the same patient and 2) to determine whether lesions treated in a multilesion intervention experience a different magnitude of restenosis than lesions undergoing single-lesion procedures.

METHODS AND RESULTS

Of 441 patients treated by Palmaz-Schatz stenting (n = 114), directional atherectomy (n = 100), or conventional balloon angioplasty (n = 227), 67 underwent multilesion procedures involving treatment of 146 lesions. A general linear model with intraclass correlation (GLIMIC) was used to calculate the coefficient of correlation (rho) of the change in the measured minimum luminal diameter (late loss) from the time of the initial procedure to 6-month angiogram among the multiple lesions within the same patient for all 441 patients. This showed no correlation among multiple lesions within the same patient for the late loss in minimum luminal diameter (rho = -0.12 [95% CI: -0.40, 0.12]), among lesions in the same vessel (rho = 0.14 [95% CI: -0.34, 0.62]), or among different vessels (rho = -0.18 [95% CI: -0.52, 0.16]), suggesting that the magnitude of late loss is independent among multiple lesions within the same patient. There was no difference (p = 0.96) between the observed incidence of zero-, one-, and two-vessel restenosis (> or = 50% diameter stenosis at follow-up) for patients with multiple-lesion treatment and that predicted assuming lesion-to-lesion independence. Similarly, there was no difference in late loss or in the overall binary restenosis rate when single-lesion procedures were compared with multilesion procedures. Multivariable analysis of the late loss in lumen diameter (which adjusted for the effects of the acute result and the device used) demonstrated no independent effect (p = 0.20) of single-lesion versus multilesion status.

CONCLUSIONS

Luminal encroachment appears to occur at independent rates among multiple lesions treated in a single patient. The observed incidence of restenosis for patients with multiple treated lesions is accurately predicted assuming independent probabilities of restenosis. Lesion-based analysis, even when including multiple treated lesions within the same patient, is thus valid for evaluating conventional angioplasty, stenting, or directional atherectomy.
Angiographic and hemodynamic determinants of myocardial ischemia during adenosine thallium-201 scintigraphy in coronary artery disease.
Authors: Nishimura S , Kimball K T , Mahmarian J J , Verani M S
Published: June 2012

BACKGROUND

Myocardial ischemia attributed to coronary steal may occur in some patients receiving pharmacological coronary vasodilation. ECG ST-segment depression is a marker of myocardial ischemia in these patients, but the factors determining the presence or absence of ischemia are not well known.

METHODS AND RESULTS

To examine the angiographic, hemodynamic, and scintigraphic determinants of adenosine-induced ischemic ST-segment depression in patients with coronary artery disease, we studied 65 consecutive patients (45 men and 20 women; mean age, 65 +/- 12 years) who showed reversible perfusion defects during adenosine (140 micrograms.kg-1.min-1 for 6 minutes) 201Tl single-photon emission computed tomography. Patients with prior myocardial infarction were excluded. Ischemic ST depression occurred in one third of the whole cohort (22 of 65 patients). The presence of coronary collateral vessels (p = 0.001), systolic blood pressure at baseline (p = 0.006), and adenosine-induced anginal chest pain (p = 0.011) were the only significant independent predictors of ischemic ST-segment depression by stepwise logistic regression analysis. Rate-pressure product at baseline, systolic blood pressure, heart rate, rate-pressure product, increase in heart rate, and rate-pressure product during adenosine infusion and maximal percent stenosis were variables also significantly related to ischemic ST depression by univariate analysis but were not predictive after the three primary variables were included in the regression model. Perfusion defect size, number of diseased vessels, and age did not correlate with ST-segment depression.

CONCLUSIONS

The presence of collaterals, which may predispose to coronary collateral steal, is the most significant correlate of ischemic ST-segment depression during adenosine infusion. Systolic blood pressure at baseline, which may affect the myocardial oxygen supply/demand ratio and anginal chest pain induced by adenosine, are additional variables related to ischemic ST-segment depression during adenosine infusion.
Cyclosporine A has no direct effect on collagen metabolism by cardiac fibroblasts in vitro.
Authors: Eleftheriades E G , Ferguson A G , Samarel A M
Published: June 2012

BACKGROUND

Cyclosporine A has been implicated in the pathogenesis of myocardial interstitial fibrosis observed in heart transplant recipients. However, other confounding variables such as posttransplantation hypertension and rejection episodes may also be responsible for interstitial fibrosis development and associated abnormalities in ventricular diastolic function. Therefore, we examined whether cyclosporine A directly or indirectly affects fibrillar collagen metabolism by cardiac fibroblasts in vitro.

METHODS AND RESULTS

Rat cardiac fibroblasts were isolated by collagenase digestion. Subconfluent cultures were then maintained (24 hours) in serum-containing or serum-free medium before addition of cyclosporine A (50-1,000 ng/mL). After an additional 24 hours, total procollagen synthesis, accumulation, and degradation were analyzed by measuring hydroxyproline content in the cell monolayer and in the ethanol-soluble and ethanol-precipitable fractions of the culture medium. mRNA levels for alpha 1(I) and alpha 1(III) procollagen polypeptides were assessed 2, 6, 12, and 24 hours after cyclosporine A treatment using Northern blot analysis. The results were compared with control cultures maintained in the absence of cyclosporine A. There were no differences in procollagen gene expression, total procollagen synthesis, accumulation, or degradation in cardiac fibroblasts treated directly with cyclosporine A, in concentrations up to 1,000 ng/mL, compared with untreated cells. In additional experiments, we examined whether cyclosporine A might stimulate the production of collagen regulatory substances by cardiac myocytes in culture. However, addition of conditioned media from neonatal myocytes maintained in the presence and absence of cyclosporine A (1,000 ng/mL) also had no effect on collagen deposition by cardiac fibroblasts.

CONCLUSIONS

We conclude that cyclosporine A has no direct effect on collagen metabolism by cultured cardiac fibroblasts in vitro. In addition, we have excluded a paracrine effect of ventricular myocytes on collagen production in the presence of cyclosporine A. These results suggest that factors other than cyclosporine A are responsible for the interstitial fibrosis observed in cardiac allografts.
Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty.
Authors: Topol E J , Bonan R , Jewitt D , Sigwart U , Kakkar V V , Rothman M , de Bono D , Ferguson J , Willerson J T , Strony J
Published: June 2012

BACKGROUND

Since the inception of coronary angioplasty, heparin with or without aspirin has been routinely given intraprocedurally to avoid coronary thrombotic complications. Recently, the direct thrombin inhibitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to determine its appropriate dose and feasibility as the sole anticoagulant during coronary angioplasty.

METHODS AND RESULTS

At 11 participating centers, 291 patients undergoing elective coronary angioplasty and pretreated with 325 mg aspirin daily were enrolled in sequential groups of intravenously administered hirulog instead of heparin as follows: group 1: bolus, 0.15 mg/kg; infusion, 0.6 mg.kg-1.hr-1 (54 patients); group 2: bolus, 0.25 mg/kg; infusion, 1.0 mg.kg-1.hr-1 (53 patients); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg.kg-1.hr-1 (44 patients); group 4: bolus, 0.45 mg/kg; infusion, 1.8 mg.kg-1.hr-1 (74 patients); and group 5: bolus, 0.55 mg/kg; infusion, 2.2 mg.kg-1.hr-1 (54 patients). The hirulog infusion was maintained for 4 hours; the primary end point was abrupt vessel closure within 24 hours of the initiation of the procedure. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) were serially monitored. Abrupt vessel closure occurred in 18 patients (6.2%). By intention to treat, the abrupt closure event rate for groups 1-3 was 11.3% compared with 3.9% in groups 4 and 5 (p = 0.052). There were no significant bleeding complications except for one patient in group 1, who received a two-unit transfusion. A dose-response curve of both ACTs and aPTTs was noted; no coronary thrombotic closures occurred in the small number of patients with ACT > 300 seconds.

CONCLUSIONS

The present study documents for the first time that it is possible to perform coronary angioplasty with an anticoagulant other than heparin in aspirin-pretreated patients. Hirulog was associated with a rapid onset, dose-dependent anticoagulant effect, minimal bleeding complications, and at doses of 1.8-2.2 mg/kg, a rate of 3.9% for abrupt vessel closure.
Cardiac tamponade. A clinical or an echocardiographic diagnosis?
Authors: Fowler N O
Published: June 2012

In most patients, cardiac tamponade should be diagnosed by a clinical examination that shows elevated systemic venous pressure, tachycardia, dyspnea, and paradoxical arterial pulse. Systemic blood pressure may be normal, decreased, or even elevated. The diagnosis is confirmed by echocardiographic demonstration of moderately large or large circumferential pericardial effusion and in most instances, of right atrial compression, abnormal respiratory variation in right and left ventricular dimensions, and in tricuspid and mitral valve flow velocities. Pulsus paradoxus may be absent with left ventricular dysfunction, atrial septal defect, regional tamponade, and positive-pressure breathing. Systemic venous pressure may be normal with localized tamponade of the left atrium or ventricle. Patients with moderately large or large pericardial effusions may have echocardiographic evidence of right atrial compression without clinical signs of elevated venous pressure or pulsus paradoxus. The majority of these patients have mild or moderate tamponade and if not subjected to pericardial drainage, should be observed closely. In some of these patients, when the etiology is known and the disease can be treated effectively with medication, e.g., nonsteroidal anti-inflammatory agents or adrenal corticosteroids in Dressler's syndrome or relapsing pericarditis, pericardial drainage may not be necessary.
Intracellular calcium homeostasis in cardiac myocytes.
Authors: Barry W H , Bridge J H
Published: June 2012

Calcium homeostasis in cardiac myocytes results from the integrated function of transsarcolemmal Ca2+ influx and efflux pathways modulated by membrane potential and from intracellular Ca2+ uptake and release caused predominantly by SR function. These processes can be importantly altered in different disease states as well as by pharmacological agents, and the resulting changes in systolic and diastolic [Ca2+]i can cause clinically significant alterations in contraction and relaxation of the heart. It may be anticipated that a rapid increase in our understanding of the pathophysiology of Ca2+ homeostasis in cardiac myocytes will be forthcoming as the powerful new tools of molecular and structural biology are used to investigate the regulation of Ca2+ transport systems.
Dose-dependent effect of aspirin on carotid atherosclerosis.
Authors: Ranke C , Hecker H , Creutzig A , Alexander K
Published: June 2012

BACKGROUND

Antiplatelet treatment with aspirin is well established as secondary prophylaxis after a transient ischemic attack or minor ischemic stroke, but the effect of aspirin treatment on the course of carotid atherosclerosis is unknown. We investigated the effect of aspirin on the initial stages of carotid atherosclerosis.

METHODS AND RESULTS

Patients were recruited from a prospective, randomized, double-blind clinical trial to compare two doses of aspirin (900 mg versus 50 mg daily) with regard to restenoses after lower limb angioplasty. Of the 383 patients admitted to the angioplasty trial, 27 patients with 104 small carotid atheroma (< 50% lumen narrowing) were examined at entry and after 1 year of aspirin treatment with the use of a high-resolution ultrasound duplex system. Disease progression and regression were defined by a change of maximal plaque area (as measured by longitudinal ultrasound sections) of more than 2 SDs of the method. The change in plaque area was significantly different for the treatment groups: Average plaque size remained unchanged after treatment with 900 mg aspirin daily but increased markedly after treatment with 50 mg aspirin daily (p = 0.011). There were significantly more lesions in the 50-mg group showing progression than in the 900-mg group (23 plaques [47%] versus 13 plaques [24%], p = 0.025). Ultrasonic disappearance of a lesion was observed only in the 900-mg group in nine cases (seven soft plaques and two ulcerative plaques, p = 0.018). The six patients on 50 mg aspirin who continued smoking during the study showed significantly more progression compared with the seven nonsmokers in the 50-mg group (17 plaques [59%] versus six plaques [30%], p = 0.038).

CONCLUSIONS

The results of our study indicate that aspirin treatment slows carotid plaque growth in a dose-dependent fashion, with a dose of 900 mg daily more efficient than 50 mg daily.
Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study.
Authors: Lowe G D , Fowkes F G , Dawes J , Donnan P T , Lennie S E , Housley E
Published: June 2012

BACKGROUND

Increased blood and plasma viscosity, hematocrit, fibrinogen, and activation of coagulation and leukocytes have been reported in patients with claudication; however, their associations with symptomatic and asymptomatic peripheral arterial disease have not been reported in an epidemiological study.

METHODS AND RESULTS

Blood and plasma viscosity, hematocrit, fibrinogen, urinary fibrinopeptide A, plasma leukocyte elastase, and uric acid were measured in a random sample of 1,581 men and women aged 55-74 years in Edinburgh, Scotland, and related to peripheral arterial stenosis (ankle-brachial systolic pressure index, ABPI) and to lower limb ischemia (intermittent claudication and reactive hyperemia test). Each variable (except fibrinopeptide A) was significantly related to prevalent symptomatic and asymptomatic peripheral arterial disease. On multivariate analysis, blood viscosity (p < 0.05) and fibrinogen (p < 0.01) were independently associated with peripheral arterial narrowing (ABPI); a positive interaction was found between fibrinogen and smoking in the association with ABPI. Plasma viscosity was associated with claudication in the presence of a given degree of arterial narrowing (odds ratio of claudication in top quintile compared with bottom quintile of plasma viscosity, 3.35; 95% CI, 1.32, 8.51). Leukocyte elastase and uric acid were each associated with reactive hyperemia independently of arterial narrowing (p < 0.01).

CONCLUSIONS

Blood rheological factors and leukocyte activation as well as arterial narrowing are associated with lower limb ischemia in the general population and may be implicated in its pathogenesis.
Silent ischemia in unstable angina is related to an altered cardiac norepinephrine handling.
Authors: Neri Serneri G G , Boddi M , Arata L , Rostagno C , Dabizzi P , Coppo M , Bini M , Lazzerini S , Dagianti A , Gensini G F
Published: June 2012

BACKGROUND

Inferential evidence suggests that silent ischemia might be related to sympathetic activity. Study of [3H]norepinephrine kinetics is a suitable tool to assess the regional sympathetic activity. This method was applied to investigate whether silent myocardial ischemia in unstable angina is related to and depends on cardiac sympathetic overactivity.

METHODS AND RESULTS

Patients with active unstable angina were compared with patients with inactive unstable angina, stable effort angina, and controls. Silent myocardial ischemia was evaluated by three 24-hour Holter monitoring periods on alternate days, and [3H]norepinephrine kinetics was assessed under rest conditions and following the cold pressor test. Simultaneously, catecholamine concentrations were measured in the aortic, coronary sinus, and peripheral venous blood. Different than the other groups (p = 0.0013), in patients with active unstable angina, the majority of silent ischemic episodes occurred without increase in heart rate. These patients had a positive coronary sinus-aorta norepinephrine gradient, both at rest and following the cold pressor test. [3H]Norepinephrine kinetics demonstrated an increased selective cardiac spillover, both at rest and, even more, after the cold pressor test. Reduced cardiac [3H]norepinephrine extraction also was found. A significant relation was found between the number of ischemic episodes or the overall duration of silent ischemia and norepinephrine spillover, both at rest and following cold application.

CONCLUSIONS

During the acute phase of unstable angina (but not in the quiescent phase or in stable effort angina), a disorder in cardiac norepinephrine handling occurs. This results in a reflex cardiac sympathetic overactivity that plays a major role in the occurrence of silent myocardial ischemia.
Cardiac troponin I. A marker with high specificity for cardiac injury.
Authors: Adams J E , Bodor G S , Dávila-Román V G , Delmez J A , Apple F S , Ladenson J H , Jaffe A S
Published: June 2012

BACKGROUND

Levels of MBCK can be increased in patients with skeletal muscle injury or renal failure in the absence of myocardial injury, causing diagnostic confusion. This study was designed to determine whether measurement of cardiac troponin I (cTnI), a myocardial regulatory protein with comparable sensitivity to MBCK, has sufficient specificity to clarify the etiology of MBCK elevations in patients with acute or chronic skeletal muscle disease or renal failure.

METHODS AND RESULTS

Of the patients (n = 215) studied, 37 had acute skeletal muscle injury, 10 had chronic muscle disease, nine were marathon runners, and 159 were chronic dialysis patients. Patients were evaluated clinically, by ECG, and by two-dimensional echocardiography. Total creatine kinase (normal, < 170 IU/L) was determined spectrophotometrically, and cTnI (normal, < 3.1 ng/mL) and MBCK (normal, < 6.7 ng/mL) were determined with specific monoclonal antibodies. Values above the upper reference limit were considered "elevated." Elevations of total creatine kinase were common, and elevations of MBCK occurred in 59% of patients with acute muscle injury, 78% of patients with chronic muscle disease and marathon runners, and 3.8% of patients with chronic renal failure. Some of the patients were critically ill; five patients were found to have had myocardial infarctions and one had a myocardial contusion. cTnI was elevated only in these patients.

CONCLUSIONS

Elevations of cTnI are highly specific for myocardial injury. Use of cTnI should facilitate distinguishing whether elevations of MBCK are due to myocardial or skeletal muscle injury.
Prognostic value and physiological correlates of heart rate variability in chronic severe mitral regurgitation.
Authors: Stein K M , Borer J S , Hochreiter C , Okin P M , Herrold E M , Devereux R B , Kligfield P
Published: June 2012

BACKGROUND

A variety of measures of heart rate variability have been devised to measure high-frequency (0.15-0.40 Hz), low-frequency (0.04-0.15 Hz), or ultralow-frequency (< 0.0033 Hz) fluctuations in sinus cycle length. Although measures of low-frequency and ultralow-frequency heart rate variability have been shown to correlate with prognosis in several populations with ischemic heart disease, their relevance to patients with primary valvular heart disease remains to be determined.

METHODS AND RESULTS

Thirty-eight patients with nonischemic causes of chronic severe mitral regurgitation who were in sinus rhythm underwent 24-hour ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular heart disease. Patients were followed for as long as 9.2 years, and end points of mortality, progression to mitral valve surgery, and development of chronic atrial fibrillation were tabulated. Time- and frequency-domain measurements of high-frequency, low-frequency, and ultralow-frequency heart rate variability were computed and compared with resting ventricular function by radionuclide cineangiography and outcome. The standard deviation of the 5-minute mean RR intervals (SDANN), a measure of ultralow-frequency heart rate variability, was correlated with left ventricular ejection fraction (r = 0.49, p = 0.002) and right ventricular ejection fraction (r = 0.43, p = 0.007), whereas low-frequency and high-frequency heart rate variabilities were not. Heart rate, ultralow-frequency heart rate variability, and, to a lesser extent, high-frequency heart rate variability exhibited significant diurnal variation, but low-frequency heart rate variability did not. Heart rate and ultralow-frequency, low-frequency, and combined low- and high-frequency heart rate variability predicted mortality and total events. The most powerful predictor of subsequent events was SDANN: Patients with reduced SDANN were significantly more likely to develop end-point events (p < 0.001) with increased progression to mitral valve surgery (p < 0.001) as well as increased early mortality (p = 0.02). In a multivariate proportional hazards model, SDANN retained independent predictive power (p = 0.001). Likewise, SDANN was the only variable that was significantly associated with the subsequent development of atrial fibrillation (relative risk, 3.1; p = 0.03).

CONCLUSIONS

Ultralow-frequency heart rate variability, as measured by SDANN, correlates with right and left ventricular performance and predicts development of atrial fibrillation, mortality, and progression to valve surgery in patients with chronic severe mitral regurgitation.
Cardiac sympathetic nervous activity in congestive heart failure. Evidence for increased neuronal norepinephrine release and preserved neuronal uptake.
Authors: Meredith I T , Eisenhofer G , Lambert G W , Dewar E M , Jennings G L , Esler M D
Published: June 2012

BACKGROUND

Increased concentrations of norepinephrine in coronary sinus plasma reported in congestive heart failure (CHF) could result from increased cardiac sympathetic nerve firing and norepinephrine release or from failure of neuronal uptake mechanisms to recapture released norepinephrine. We have applied neurochemical indexes of cardiac sympathetic nerve function in heart failure patients to delineate the underlying neural pathophysiology.

METHODS AND RESULTS

Cardiac norepinephrine synthesis, assessed from the cardiac overflow of the norepinephrine precursor dihydroxyphenylalanine (DOPA), intraneuronal metabolism estimated from the overflow of the intraneuronal metabolite dihydroxyphenylglycol (DHPG), neuronal norepinephrine reuptake assessed from the fractional extraction of plasma-tritiated norepinephrine and production of tritiated DHPG across the heart, and norepinephrine spillover to plasma were examined in eight patients with CHF caused by coronary artery disease (left ventricular ejection fraction of 26 +/- 5%, mean +/- SEM) and 14 age-matched healthy subjects. Cardiac norepinephrine spillover was increased eightfold in CHF subjects (127 ng/min versus 14 ng/min in healthy subjects; standard error of the difference [SED], 8 ng/min; P < .002), and cardiac DOPA was increased twofold (P < .02). The fractional extraction of tritiated norepinephrine across the heart was marginally less in CHF subjects (0.63 versus 0.73 in normal subjects; SED, 0.02), but the extent to which pharmacological neuronal uptake blockade with desipramine reduced the cardiac extraction of tritiated norepinephrine (by 71% versus 73% in normal subjects) and reduced the production of tritiated DHPG derived from uptake and intraneuronal metabolism of tritiated norepinephrine was similar in CHF patients and healthy subjects.

CONCLUSIONS

The marked increase in norepinephrine spillover from the heart in CHF attributable to coronary artery disease results primarily from an increase in sympathetic nerve firing and neuronal release of norepinephrine, not from faulty neuronal reuptake of norepinephrine.
Regional differences in sympathetic reinnervation after human orthotopic cardiac transplantation.
Authors: Wilson R F , Laxson D D , Christensen B V , McGinn A L , Kubo S H
Published: June 2012

BACKGROUND

In the majority of humans > or = 1 year after cardiac transplantation, cardiac norepinephrine (NE) stores reappear, suggesting late sympathetic reinnervation.

METHODS AND RESULTS

To determine whether there are regional differences in reinnervation, we measured markers of sympathetic reinnervation of the sinus node (SN) and left ventricle (LV) in five early transplant recipients (< or = 4 months after cardiac transplantation), 45 late transplant recipients (> or = 1 year after cardiac transplantation), and seven normally innervated control patients. SN reinnervation was defined as an increase in heart rate by more than five beats per minute after injection of tyramine into the artery supplying the SN. LV reinnervation was defined as a measurable LV NE release after left main coronary injection of 8 micrograms/kg tyramine. In 13 patients with previously known LV reinnervation, regional LV reinnervation was assessed by NE release after subselective injection of tyramine (4 micrograms/kg) into the proximal left anterior descending and circumflex arteries. Five of five patients < or = 4 months after cardiac transplantation had no change in heart rate and no LV NE release, confirming early, total denervation. In contrast, > or = 1 year after cardiac transplantation, tyramine caused a heart rate increase (eight to 49 beats per minute) in 32 of 45 patients and LV NE release in 33 of 45. Although LV NE release was correlated with the change in heart rate in late cardiac transplantation recipients (r = .61), eight of 45 had only heart rate response, nine had only LV NE release, and four had neither. In late cardiac transplantation recipients with LV reinnervation, tyramine caused NE release from both the anterior descending and circumflex perfusion fields in 10 of 14, but one of 14 patients released NE only after circumflex tyramine and three of 14 only after left anterior descending tyramine stimulation. Tyramine caused a marked heart rate increase and LV NE release in all control patients.

CONCLUSIONS

Sympathetic reinnervation after cardiac transplantation is regionally heterogeneous. SN reinnervation is not associated necessarily with LV reinnervation, and LV reinnervation can involve the anterior and posterior walls together or separately.
Temperature-guided radiofrequency catheter ablation with very large distal electrodes.
Authors: Langberg J J , Gallagher M , Strickberger S A , Amirana O
Published: June 2012

BACKGROUND

Previous studies have shown that the size of lesions produced by radiofrequency catheter ablation correlates with the temperature and surface area of the electrode-tissue interface. The purpose of the present study was to compare the effects of ablation using very large distal electrodes (8F, 8 and 12 mm long) with those made by a conventional radiofrequency ablation catheter (distal electrode 8F, 4 mm long).

METHODS AND RESULTS

Each catheter had a thermistor in the tip of the distal electrode. Radiofrequency energy (500 kHz) was supplied by a generator that continuously monitored temperature and produced up to 100 W. In 10 dogs, each of the three ablation catheters were introduced percutaneously and positioned under fluoroscopic guidance at disparate left ventricular endocardial sites. Radiofrequency power output was titrated to achieve a temperature of 80 degrees C for 60 seconds at each ablation site. The power required to produce a steady-state temperature of 80 degrees C was directly proportional to electrode size (15 +/- 7, 46 +/- 15, and 62 +/- 32 W using the 4-mm-, 8-mm-, and 12-mm-long electrodes, respectively). Lesions produced by the 8-mm electrode were nearly twice as deep (11 +/- 2.4 versus 6 +/- 1.2 mm, P < .001) and four times as large (905 +/- 410 versus 210 +/- 100 mm3, P < .001) as those made with a conventional 4-mm electrode. Lesions produced by the 12-mm electrode were intermediate in size (depth, 8 +/- 1.2 mm; volume, 465 +/- 225 mm3) and sometimes were associated with charring and crater formation. Ablation with the larger electrodes caused a drop in arterial pressure and more ventricular ectopy than ablation using a 4-mm distal electrode.

CONCLUSIONS

Thermistor-equipped elongated ablation electrodes coupled to high-power outputs can reproducibly produce lesions approximately 1 cm in diameter. This system may prove useful for ablation of ventricular tachycardias in patients with coronary artery disease.