bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.
Authors: Jude B , Agraou B , McFadden E P , Susen S , Bauters C , Lepelley P , Vanhaesbroucke C , Devos P , Cosson A , Asseman P 
Published: June 2012

BACKGROUND
Platelet activation plays a pivotal role in the pathogenesis of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation through their ability to synthesize tissue factor (TF). The aim of this study was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina.

METHODS AND RESULTS
We studied 26 patients with unstable angina (10 +/- 5 hours after the onset of the last episode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cells (isolated by gradient centrifugation and incubated for 16 hours, with or without endotoxin stimulation), levels of plasma prothrombin fragment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, monocyte TF activity did not differ from that in patients with stable angina. Mean levels of F1 + 2 and of fibrinogen did not differ significantly between groups. Only in the unstable angina group, a modest correlation was found between fibrinogen (r = .72, P = .005) and F1 + 2 levels (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimulated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapsed from the beginning of the most recent episode of pain (.61 < r < .72, .02 < P < .0001). By contrast, there was no correlation between these variables and the time from onset of pain in patients with acute myocardial infarction.

CONCLUSIONS
A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.
Hypertrophic obstructive cardiomyopathy. Initial results and long-term follow-up after Morrow septal myectomy.
Authors: ten Berg J M , Suttorp M J , Knaepen P J , Ernst S M , Vermeulen F E , Jaarsma W 
Published: June 2012

BACKGROUND
This study was performed to assess the initial results and long-term follow-up of Morrow septal myectomy for patients with hypertrophic obstructive cardiomyopathy (HOCM).

METHODS AND RESULTS
We studied 38 consecutive patients with HOCM (age, 13 to 74 years) who underwent a Morrow septal myectomy between 1977 and 1992. There were no perioperative deaths, and the postoperative course was uneventful for all except 2 of the patients. One patient required implantation of a pacemaker due to a complete heart block, and in 1 patient a small ventricular septal defect was caused. Follow-up (mean, 6.8 years) was 100% complete. No patient was reoperated for recurrent HOCM. All except 1 patient experienced a major functional improvement with a decrease of the mean New York Heart Association functional class from 3.0 before operation to 1.5 at follow-up (P < .001). Symptoms persisting during follow-up were angina pectoris in 3 of 22 patients (14%), dyspnea in 6 of 30 patients (20%), dizzy spells in 2 of 12 patients (17%), and syncope in 2 of 10 patients (20%). During follow-up no HOCM related death occurred. All patients were restudied by Doppler echocardiography. The peak gradient in the left ventricular outflow tract decreased from 72 +/- 30 mm Hg (range, 31 to 144 mm Hg) to 6 +/- 4 mm Hg (range, 0 to 20; P < .001). A systolic anterior movement was seen in 8 patients (21%) compared with 32 patients (97%) before the operation (P < .001). The left ventricular outflow tract diameter increased from 17 +/- 3 mm (range, 10 to 23 mm) to 22 +/- 3 mm (range, 15 to 33 mm; P < .001), and the mean subaortic septal thickness decreased from 23 +/- 5 mm (range, 15 to 35 mm) to 15 +/- 6 mm (range, 8 to 30 mm; P < .001).

CONCLUSIONS
Morrow septal myectomy for patients with HOCM is a safe procedure with an excellent clinical and Doppler echocardiographic long-term follow-up.
Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response.
Authors: Hiatt W R , Wolfel E E , Meier R H , Regensteiner J G 
Published: June 2012

BACKGROUND
In patients with intermittent claudication, a supervised walking exercise program increases peak exercise performance and community-based functional status. Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment. However, the potential benefits of training modalities other than walking exercise, such as strength training, have not been critically evaluated in this patient population. The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance.

METHODS AND RESULTS
Twenty-nine patients with disabling claudication were randomized to 12 weeks of supervised walking exercise on a treadmill (3 h/wk at a work intensity sufficient to produce claudication), strength training (3 h/wk of resistive training of five muscle groups of each leg), or a nonexercising control group. Graded treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance. After 12 weeks, patients in the treadmill training program had a 74 +/- 58% increase in peak walking time as well as improvements in peak oxygen consumption (VO2) and the onset of claudication pain. Patients in the strength-trained group had a 36 +/- 48% increase in peak walking time but no change in peak VO2 or claudication onset time. Control subjects had no changes in any of these measures over the 12-week period. After the first 12 weeks, patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training. This resulted in an additional 49 +/- 53% increase in peak walking time (total of 128 +/- 99% increase over the 24 weeks). After the initial 12 weeks, patients in the strength-trained group began 12 weeks of supervised treadmill training, and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise. The combined strength and treadmill training program and treadmill training after 12 weeks of strength training resulted in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone.

CONCLUSIONS
A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication, with continued improvement over 24 weeks of training. In contrast, 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise. Finally, strength training, whether sequential or concomitant, did not augment the response to a walking exercise program.
Class III antiarrhythmic drug action in experimental atrial fibrillation. Differences in reverse use dependence and effectiveness between d-sotalol and the new antiarrhythmic drug ambasilide.
Authors: Wang J , Feng J , Nattel S 
Published: June 2012

BACKGROUND
Drug therapy to maintain sinus rhythm in patients with atrial fibrillation (AF) is limited by adverse effects and inadequate efficacy. There has been an increased interest in the use of class III drugs to treat AF, and several new agents have been developed, but there is little information available about mechanisms of class III drug action in AF. The present study was designed to compare the effects of two class III agents, d-sotalol and ambasilide, in dog models of experimental AF.

METHODS AND RESULTS
A previously developed dog model of sustained vagotonic AF was used to assess the ability of equal loading doses of d-sotalol and ambasilide (2 mg/kg, followed by maintenance infusions), to terminate AF and prevent its induction. At this dose, ambasilide terminated AF in 12 of 12 dogs and prevented AF induction in 10 of 12 dogs; d-sotalol terminated AF in 1 of 8 dogs (P = .001 versus ambasilide) and prevented AF induction in none of 8 dogs (P = .002). An additional dose of d-sotalol (cumulative load, 8 mg/kg) terminated AF in 7 of 8 dogs and prevented induction in 5 of 8 dogs. In an additional 6 dogs with sterile pericarditis and inducible AF, ambasilide prevented AF induction in all 6. An equal dose of d-sotalol (2 mg/kg) failed to suppress AF induction in any dog, but 8 mg/kg of d-sotalol suppressed AF induction in all. Atrial effective refractory period (AERP) was increased by both drugs. However, the effects of d-sotalol on AERP showed strong reverse use dependence, whereas those of ambasilide did not. Neither ambasilide nor d-sotalol significantly altered conduction velocity, and both increased ventricular refractoriness, with d-sotalol once again showing more reverse use dependence. Effective doses of both agents increased AERP and the wavelength for atrial reentry at rapid rates, slowing atrial activation and terminating the arrhythmia.

CONCLUSIONS
The class III drugs d-sotalol and ambasilide terminate AF by increasing AERP and the wavelength for reentry. Ambasilide, which has been reported to block both the rapid and slow components of the delayed rectifier (IKr and IKs), shows less reverse use dependence of effects on refractoriness than the pure IKr blocker d-sotalol, possibly explaining the greater effectiveness of ambasilide at an equal dose level. These results indicate that class III drugs can exhibit different profiles of rate-dependent action on AERP and suggest that it may be possible to develop agents that have more desirable rate-dependent profiles than pure blockers of Ikr.
Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men.
Authors: Ridker P M , Hennekens C H , Cerskus A , Stampfer M J 
Published: June 2012

BACKGROUND
Plasma levels of D-dimer, the primary degradation product of cross-linked fibrin, are elevated in several acute thrombotic disorders. However, whether elevated D-dimer levels among healthy individuals are associated with future coronary thrombosis is unknown.

METHODS AND RESULTS
To evaluate whether levels of D-dimer are associated with the occurrence of future myocardial infarction (MI) among apparently healthy men, levels were measured in plasma samples collected at baseline from 296 participants in the Physicians' Health Study who later developed a first MI and from an equal number of age- and smoking status-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. In univariate analyses, baseline plasma concentrations of D-dimer in the upper ranges of normal were associated with elevated risks of MI. Specifically, the relative risk of future MI for individuals with baseline D-dimer concentration exceeding the 95th percentile of the control distribution was two times higher than that of individuals with lower levels (relative risk [RR], 2.02; 95% confidence interval [CI], 1.04 to 4.02; P = .04). This association persisted in multivariate analyses controlling for nonlipid cardiovascular risk factors (RR, 2.12; 95% CI, 1.05 to 4.28; P = .04) and for lipoprotein(a) (RR, 2.02; 95% CI, 1.04 to 3.94; P = .03). In contrast, this association was attenuated and no longer statistically significant in analyses that controlled for total and high-density lipoprotein cholesterol (RR, 1.74; 95% CI, 0.78 to 3.91; P = .2) or for endogenous tissue-type plasminogen activator and its primary inhibitor, plasminogen activator inhibitor type 1 (RR, 1.58; 95% CI, 0.67 to 3.77; P = .3).

CONCLUSIONS
Elevated levels of D-dimer are associated with increased risks of future MI, although they do not appear to be an independent predictor when other risk factors are considered. As the presence of D-dimer in plasma reflects ongoing fibrin degradation, these data support the hypothesis that activation of the endogenous fibrinolytic system occurs many years in advance of coronary arterial occlusion.
Relation of regional function, perfusion, and metabolism in patients with advanced coronary artery disease undergoing surgical revascularization.
Authors: vom Dahl J , Eitzman D T , al-Aouar Z R , Kanter H L , Hicks R J , Deeb G M , Kirsh M M , Schwaiger M 
Published: June 2012

BACKGROUND
Imaging of myocardial glucose metabolism using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) has been proposed for identification of tissue viability in patients with advanced coronary artery disease. This study was designed to evaluate the predictive value of flow and metabolic imaging for functional recovery after revascularization in myocardial segments of varying degrees of dysfunction.

METHODS AND RESULTS
Thirty-seven patients (mean age, 59 +/- 11 years) with coronary artery disease and impaired left ventricular function (ejection fraction, 34 +/- 10%) were studied with PET using FDG and [13N]ammonia before surgical coronary revascularization (3 +/- 1 grafts per patient). Tissue was scintigraphically characterized as normal, nonviable (concordant reduction of perfusion and FDG uptake), viable without discordance of perfusion and metabolism (mildly reduced perfusion and metabolism), or ischemically compromised (mismatch of reduced perfusion and maintained FDG uptake). Functional outcome was assessed by serial radionuclide ventriculography before and at 13 +/- 13 weeks (median interval of 8 weeks) after coronary revascularization. Preoperatively impaired regional wall motion improved significantly in ischemically compromised (mismatch) revascularized segments but not in nonviable myocardium or in viable myocardium without discordance of perfusion and metabolism. The negative predictive value of PET for functional recovery was 86%, whereas the positive predictive value in revascularized regions ranged from 48% to 86% depending on severity of baseline wall motion abnormalities.

CONCLUSIONS
PET identifies metabolically active tissue, which benefits from revascularization. Although the negative predictive value of PET for recovery was high, functional improvement of viable but ischemically compromised tissue was less frequent than previously reported. The predictive value of PET was highest in left ventricular segments with severe dysfunction and a mismatch or reduced perfusion but preserved metabolism. Integration of PET, angiographic, and functional data is necessary for the optimal selection of patients with advanced coronary artery disease and impaired left ventricular function for revascularization.
Cardiac tamponade complicating proximal aortic dissection. Is pericardiocentesis harmful?
Authors: Isselbacher E M , Cigarroa J E , Eagle K A 
Published: June 2012

BACKGROUND
Cardiac tamponade frequently complicates acute proximal aortic dissection and is one of the most common causes of death from aortic dissection. Well-defined strategies for the management of acute aortic dissection now exist; however, little is known about how best to manage the hemopericardium that may complicate it.

METHODS AND RESULTS
Using a computer-based review, we retrospectively identified 10 patients presenting to our hospital over a 13-year period who were diagnosed with both aortic dissection and cardiac tamponade. All 10 had proximal dissections. Three of the 10 presented as the sudden onset of fatal electromechanical dissociation, 6 presented with hypotension, and 1 was normotensive on presentation. Of the 7 hypotensive or normotensive patients diagnosed with cardiac tamponade, 4 underwent successful pericardiocentesis while awaiting surgery. At time intervals of 5 to 40 minutes after their pericardiocenteses, 3 of the 4 patients experienced sudden onset of electromechanical dissociation and death; the fourth patient survived and underwent surgical repair. Of the 3 hypotensive or normotensive patients who had either no pericardiocentesis or an unsuccessful pericardiocentesis, all 3 underwent successful surgical repair and survived.

CONCLUSIONS
In this study, patients with an aortic dissection complicated by cardiac tamponade have an early mortality of 60%. While 3 of the 10 died from electromechanical dissociation immediately upon presentation, the 3 other deaths all occurred shortly after successful pericardiocentesis, a procedure undertaken to stabilize them. While the number of patients in this series is small, the observations do raise the possibility that in patients with cardiac tamponade complicating aortic dissection pericardiocentesis could be harmful rather than beneficial. Possible mechanisms for why the performance of pericardiocentesis might destabilize such patients are proposed.
Inhibition of growth of thrombus on fresh mural thrombus. Targeting optimal therapy.
Authors: Meyer B J , Badimon J J , Mailhac A , Fernández-Ortiz A , Chesebro J H , Fuster V , Badimon L 
Published: June 2012

BACKGROUND
Residual mural thrombus on severely damaged arterial wall is very thrombogenic. We tested the hypothesis that direct thrombin inhibition will block thrombus growth on fresh thrombus better than indirect thrombin inhibition, cyclooxygenase inhibition, or both.

METHODS AND RESULTS
A fresh mural thrombus was formed by directly perfusing fresh porcine blood for 5 minutes over severely damaged arterial wall at a high shear rate in a well-characterized ex vivo perfusion system. The average platelet (P) and fibrinogen (F) deposition (D) achieved in 5 minutes were 382 +/- 32 x 10(6) platelets/cm2 and 296 +/- 36 x 10(12) fibrinogen molecules/cm2, respectively. Thrombus growth on the fresh mural thrombus was quantitated by directly perfusing blood from pigs with 111In-labeled platelets and 125I-labeled fibrinogen for an additional 5 minutes over the preformed mural thrombus. Treatment included recombinant hirudin (1 mg/kg per hour IV) as a probe for thrombin, aspirin (5 mg/kg IV) as a platelet inhibitor of cyclooxygenase, heparin (moderate, 100 IU/kg per hour IV; high-dose, 250 IU/kg per hour IV) as an indirect thrombin inhibitor, and heparin (100 IU/kg per hour) plus aspirin (5 mg/kg IV). Thrombus growth as measured by labeled PD (x 10(6)/cm2) and FD (x 10(12) molecules/cm2) was mildly but not significantly reduced by aspirin (1034 +/- 92 and 436 +/- 78, respectively) compared with baseline (1113 +/- 67 and 545 +/- 52, respectively). Inhibition of thrombus growth with heparin was dose dependent. A regression analysis showed an inverse correlation of PD and FD with mean plasma heparin concentrations (r = -.81, P = .0001 and r = -.49, P = .0007, respectively). Recombinant hirudin led to a profound inhibition of thrombus growth (PD, 30 +/- 12; FD, 109 +/- 21), which was significant compared with all groups, even the highest dosage of heparin (250 IU/kg per hour).

CONCLUSIONS
Specific thrombin inhibition markedly inhibits platelet and fibrinogen deposition onto fresh mural thrombus at a high shear rate. Aspirin alone or in combination with heparin has little effect on evolving thrombosis. Heparin dose dependently reduces thrombus growth, but even the highest dosage is less effective than hirudin. Thrombin appears to be the primary activator of platelets by fresh thrombus.
Relation between shock-related myocardial injury and defibrillation efficacy of monophasic and biphasic shocks in a canine model.
Authors: Osswald S , Trouton T G , O'Nunain S S , Holden H B , Ruskin J N , Garan H 
Published: June 2012

BACKGROUND
Certain biphasic waveforms with specific time ratios of positive and negative components require less energy for successful defibrillation of the fibrillating ventricles than monophasic waveforms. However, if more efficient waveforms were also to be associated with more injurious effects on myocardial function, they might not provide a true biological advantage. This study investigates the relation between defibrillation efficacy and potential toxicity of monophasic and asymmetric, single capacitor, biphasic waveforms with equal durations of positive and negative components.

METHODS AND RESULTS
The myocardial lactate extraction rate (LER) was used to measure the injurious effects on myocardial oxidative metabolism of two synchronized 35-J shocks in sinus rhythm. LER, mean arterial pressure (MAP) and, in a subset of experiments, cardiac output (CO) and coronary blood flow (CBF) were measured at baseline, 30 seconds, 60 seconds, 90 seconds, 150 seconds, 300 seconds, and 600 seconds after the shocks. In 12 dogs, three different waveforms (M 10: monophasic 10 milliseconds; BI 10: biphasic 10 milliseconds; BI 20: biphasic 20 milliseconds) were tested as series of two consecutive shocks (60 seconds apart) resulting in a total of 36 sets of data. At baseline, LER was 25 +/- 11%. After monophasic shocks, LER decreased significantly more than after biphasic shocks (LER at 150 seconds: M 10: -6 +/- 31% versus BI 10: 21 +/- 15% versus BI 20: 21 +/- 16%; M 10 versus BI 10 and M 10 versus BI 20, P < .05) and showed also a slower recovery (LER at 300 seconds: M 10: 1 +/- 24% versus BI 10: 20 +/- 11% versus BI 20: 20 +/- 15%; M 10 versus BI 10 and M 10 versus BI 20, P < .05). The maximal decrease in LER was 41 +/- 27% for M 10 compared with 18 +/- 15% for BI 10 and 15 +/- 11% for BI 20 (both, M 10 versus BI 10 and M 10 versus BI 20, P < .05). There was a similar decrease in CO and MAP, with the lowest MAP after monophasic shocks. The maximal decrease in MAP was significantly greater after M 10 compared with BI 20 (-29 +/- 15 mm Hg versus -13 +/- 11 mm Hg, P < .05). The defibrillation threshold was 18.6 +/- 8 J for M 10 compared with 11.5 +/- 4.0 J for BI 10 (P < .05) and 15.0 +/- 6.1 J for BI 20, respectively (P = NS).

CONCLUSIONS
Our results suggest that these specific biphasic waveforms are associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance. Given their higher defibrillation efficacy as well, biphasic waveforms may provide important long-term benefits in patients receiving frequent shocks from implantable cardioverter-defibrillators.