bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of dual-chamber permanent pacing in patients with obstructive hypertrophic cardiomyopathy with symptoms refractory to verapamil and beta-adrenergic blocker therapy.
Authors: Fananapazir L , Cannon R O , Tripodi D , Panza J A 
Published: June 2012

BACKGROUND
Patients with obstructive hypertrophic cardiomyopathy (HCM) with symptoms refractory to drugs (beta-blockers or verapamil) are candidates for cardiac surgery (left ventricular septal myectomy or mitral valve replacement). The present study examines prospectively the ability of dual-chamber (DDD) pacing to improve symptoms and relieve left ventricular outflow obstruction in such patients.

METHODS AND RESULTS
Forty-four consecutive patients with obstructive HCM who had failed to benefit from pharmacotherapy underwent treadmill exercise tests, echocardiography, and cardiac catheterization before and 1.5-3 months after implantation of a DDD pacemaker. Symptoms (angina, dyspnea, palpitations, presyncope, and syncope), New York Heart Association functional class status (1.7 +/- 0.7 versus 3.4 +/- 0.5, p less than 0.00001), and exercise durations were improved at follow-up evaluation. This was associated with significant reduction in left ventricular outflow tract gradient (38 +/- 38 versus 87 +/- 43 mm Hg, p less than 0.0001) and significant increases in cardiac output and systemic arterial pressures. Notably, when pacing was discontinued and comparisons were made in sinus rhythm, treadmill exercise durations were greater and left ventricular outflow tract gradients were less at the follow-up evaluation compared with the baseline study.

CONCLUSIONS
DDD pacing is an effective alternative to surgery in most patients with obstructive HCM with drug-refractory symptoms. The beneficial effects of pacing continue to be evident when pacing is acutely discontinued.
Lipids and other risk factors selected by discriminant analysis in symptomatic patients with supra-aortic and peripheral atherosclerosis.
Authors: Vigna G B , Bolzan M , Romagnoni F , Valerio G , Vitale E , Zuliani G , Fellin R 
Published: June 2012

BACKGROUND
Different patterns of risk factors might be related to the involvement of specific vascular districts by atherosclerosis. In this sense, many investigations have addressed coronary artery disease, whereas extracoronary atherosclerosis has received less extensive attention.

METHODS AND RESULTS
Vascular risk factors, with particular attention to lipid parameters (total cholesterol [TC]; triglycerides; high density lipoprotein cholesterol [HDL-C], HDL2 and HDL3 cholesterol [HDL2-C, HDL3-C]), were evaluated by means of univariate and multivariate (discriminant) analysis in a group of 169 patients (128 men and 41 women; mean ages, 58 +/- 7 and 62 +/- 7 years, respectively) with clinically and angiographically demonstrated atherosclerosis of the supra-aortic trunk and/or lower limbs. Patients with coronary artery disease were excluded from this study. The control group consisted of 140 age- and sex-matched individuals. By univariate analysis, smoking was more closely associated with peripheral atherosclerosis, whereas blood pressure was higher in patients with supra-aortic disease. Unrecognized diabetes mellitus was a frequent finding in patients with peripheral disease. The percentage of hyperlipidemias was fourfold higher in patients than in control subjects, with differences consisting of higher triglycerides and lower HDL-C, HDL2-C, and HDL3-C concentrations. By discriminant analysis, high correct classification (CC) rates were achieved in the various patient subgroups on the basis of variables selected from the statistical function. In male patients with peripheral disease, the variables HDL-C, smoking, diastolic blood pressure, uric acid, and glucose, in that order, yielded a CC in 90.4% of the cases; in female patients, smoking, TC/HDL-C, and body mass index gave a CC rate of 95.9%. In men with cerebral disease, the selected variables TC/HDL-C, diastolic blood pressure, and TC yielded a CC of 90.7%; in women, uric acid, TC/HDL-C, and fibrinogen levels produced a CC rate of 89.2%.

CONCLUSIONS
Risk profiles in atherosclerosis of the supra-aortic trunks and lower limbs seem to differ in relation to gender and circulatory district involved. The importance of lipid parameters, in particular HDL-C, HDL2-C, and TC/HDL-C, as extracoronary risk factors is further confirmed.
Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions.
Authors: de Graaf J C , Banga J D , Moncada S , Palmer R M , de Groot P G , Sixma J J 
Published: June 2012

BACKGROUND
Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation. An inhibitory role on platelet adhesion has been suggested from experiments with washed platelets under static conditions. We have determined whether endothelium-derived and exogenous NO also regulates platelet adhesion in whole blood under flow conditions.

METHODS AND RESULTS
The effect of endothelium-derived NO was studied by the addition of specific inhibitors of NO production, L-N-monomethyl arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO), to a perfusion system in which both endothelial cells and their matrices were present. A concentration-dependent increase in platelet adhesion to the matrix was found with a maximum inhibition at a concentration of 2 mM L-NMMA and 0.1 mM L-NIO. The effect was dependent on the presence of endothelial cells, because no increase in platelet adhesion was observed in their absence. The effect of exogenous NO was tested in a specially devised perfusion system in which the NO was introduced at the site of adhesion by means of a porous membrane on which an extracellular matrix of endothelial cells was present. Inhibition of platelet adhesion by NO was found at all shear rates tested and after all perfusion periods.

CONCLUSIONS
These results demonstrate that NO is a potent inhibitor of platelet adhesion under flow conditions and thereby contributes to the regulatory role of vascular endothelial cells on platelet-vessel wall interaction.
Recombinant tissue-type plasminogen activator and immediate angioplasty in acute myocardial infarction. One-year follow-up. The European Cooperative Study Group.
Authors: Arnold A E , Simoons M L , Van de Werf F , de Bono D P , Lubsen J , Tijssen J G , Serruys P W , Verstraete M 
Published: June 2012

BACKGROUND
The European Cooperative Study Group conducted two randomized trials in patients with suspected myocardial infarction to assess the effect of 100 mg single-chain recombinant tissue-type plasminogen activator (rt-PA, alteplase) on enzymatic infarct size, left ventricular function, morbidity and mortality relative to placebo (alteplase/placebo trial) and to assess the effect of immediate percutaneous transluminal coronary angioplasty (PTCA) in addition to alteplase (alteplase/PTCA trial). One-year follow-up results are reported.

METHODS AND RESULTS
In the alteplase/placebo trial, 721 patients with chest pain of less than 5 hours and extensive ST-segment elevation were allocated at random to 100 mg alteplase or placebo (double-blind) over 3 hours. In the alteplase/PTCA trial, 367 similar patients received alteplase and subsequently were allocated at random to immediate coronary angiography and angioplasty of the infarct-related vessel or control. All patients received aspirin and intravenous heparin. In the alteplase/placebo trial, mortality during the first year was reduced by 36% with alteplase (from 9.3% to 5.6%; difference, -3.7%; 95% confidence interval, -7.5% to 0.2%). Revascularization was performed more frequently after alteplase, and more patients in the alteplase group were in New York Heart Association functional class I or II. Reinfarction tended to occur more frequently after alteplase than after placebo. In the alteplase/PTCA trial, reinfarction was less common after immediate PTCA, and revascularization procedures were less frequent. However, this benefit was offset by a high rate of immediate reocclusion and early recurrent ischemia and by higher mortality at 1 year (9.3% versus 5.4%; difference, 3.9%; 95% confidence interval, -1.5% to 9.2%) in the invasive group. In a multivariate analysis of 1,043 hospital survivors, mortality after discharge was related to coronary anatomy, left ventricular function, age, and previous infarction but not to initial treatment allocation. Reinfarction after hospital discharge tended to be more common after alteplase and related to coronary anatomy.

CONCLUSIONS
Benefit from treatment with alteplase, heparin, and aspirin is not diminished at 1 year. Routine immediate PTCA does not confer additional benefit. Prognosis after hospital discharge mainly is determined by coronary anatomy and residual left ventricular function and is unrelated to initial treatment assignment.
Intravascular ultrasound imaging of coronary arteries. Is three layers the norm?
Authors: Fitzgerald P J , St Goar F G , Connolly A J , Pinto F J , Billingham M E , Popp R L , Yock P G 
Published: June 2012

BACKGROUND
The purpose of this study was to evaluate the significance of the three-layered appearance of coronary arteries in adolescence and adults from intravascular ultrasound scans and to correlate these observations with histopathology.

METHODS AND RESULTS
Sixteen intact hearts were excised at autopsy from patients with no clinical history of coronary artery disease. The patients' ages ranged from 13 to 55 years. A 30-MHz ultrasound imaging catheter was used to obtain images throughout the epicardial coronary vasculature. A total of 72 image cross sections was marked by epivascular sutures, and the corresponding histological sections were examined. Ultrasound images were classified into two groups: images exhibiting three-layered appearance and images without distinct layering. Histological analysis revealed a significantly greater degree of intimal thickening in segments with three layers (243 +/- 105 microns) than in nonlayered segments (112 +/- 55 microns). Discriminant analysis of these data predicted the threshold between the two groups to be 178 microns. Measurements of medial thickness were not different between these two groups (235 +/- 61 versus 210 +/- 76 microns). In the nonlayered group, the average patient age was 27.1 +/- 8.5 years, whereas in the three-layered groups, the average age was 42.8 +/- 9.8 years.

CONCLUSIONS
The intracoronary ultrasound image appearance of young, morphologically normal coronary artery walls is homogeneous without layering. A three-layered appearance suggests the presence of at least 178 microns of intimal thickening and is seen more frequently with advancing age.
A new strategy for the assessment of viable myocardium and regional myocardial blood flow using 15O-water and dynamic positron emission tomography.
Authors: Yamamoto Y , de Silva R , Rhodes C G , Araujo L I , Iida H , Rechavia E , Nihoyannopoulos P , Hackett D , Galassi A R , Taylor C J 
Published: June 2012

BACKGROUND
We have developed a new measure of myocardial viability, the water-perfusable tissue index (PTI), which is calculated from transmission, C15O, and H2(15)O positron emission tomography (PET) data sets. It is defined as the proportion of the total anatomical tissue within a given region of interest (ROI) that is capable of rapidly exchanging water and has units g (perfusable tissue)/g (total anatomical tissue). The aim of this study was to assess the prognostic value of PTI in predicting improvement in regional wall motion after successful thrombolysis for acute myocardial infarction (AMI) and to measure the myocardial blood flow to the perfusable tissue (MBFp, ml/min/g [perfusable tissue]). Furthermore, PTI was compared with 18FDG metabolic imaging in patients with old myocardial infarction (OMI).

METHODS AND RESULTS
PET scans were performed in healthy volunteers (group 1, n = 8), patients with OMI (group 2, n = 15), and in patients who were successfully thrombolysed after an AMI (group 3, n = 11). Systolic wall thickening was measured by two-dimensional echocardiography within 2-4 days of AMI and after 4 months to assess contractile recovery. In the healthy volunteers, MBFp was 0.95 +/- 0.13 ml/min/g (perfusable tissue). PTI in these regions was 1.08 +/- 0.07 g (perfusable tissue)/g (total anatomical tissue), which was consistent with all normal myocardium being perfusable by water. In the OMI group, the ratio of the relative 18FDG activity to the relative MBFp defect (metabolism-flow ratio) was calculated for each asynergic segment. Regions in which the metabolism-flow ratio was greater than or equal to 1.20 were considered reversibly injured, whereas those in which the ratio was less than 1.20 were deemed irreversibly injured. PTI in the former group of regions (n = 9) was 0.75 +/- 0.14 g (perfusable tissue)/g (total anatomical tissue) and was significantly higher than in irreversibly injured regions (n = 6) (0.53 +/- 0.12 g [perfusable tissue]/g [total anatomical tissue], p less than 0.01). Values of MBFp were similar in these segments. Seven of 12 segments in the AMI patients showed improved systolic wall thickening on follow-up. PTI in these recovery segments was 0.88 +/- 0.10 g (perfusable tissue)/g (total anatomical tissue) (p = NS versus control). PTI in the nonrecovery regions was 0.53 +/- 0.11 g (perfusable tissue)/g (total anatomical tissue), which was similar to the segments in group 2 in which 18FDG uptake was absent. MBFp was similar in both the recovery and nonrecovery segments in the subacute phase.

CONCLUSIONS
These data indicate that PTI may be a good prognostic indicator for the recovery of contractile function after successful thrombolysis and show that myocardial viability may be assessed by PET without metabolic imaging.
Sinus node automaticity during atrial fibrillation in isolated rabbit hearts.
Authors: Kirchhof C J , Allessie M A 
Published: June 2012

BACKGROUND
It is still unclear what role the sinus node may play in the genesis or perpetuation of atrial fibrillation. Therefore, we studied the electrical activity in different regions of the sinus node during atrial fibrillation.

METHODS AND RESULTS
In Langendorff-perfused rabbit hearts, paroxysms of atrial fibrillation were induced by burst pacing. Standard microelectrode techniques were used to record transmembrane potentials from different regions of the sinus node. We found that during atrial fibrillation, a high degree (5:1) of sinoatrial entrance block was present that protected the pacemaker fibers in the center of the sinus node against the high rate of fibrillatory impulses. As a result, the true pacemaker fibers in the center of the node were activated with only a slightly higher average rate than during sinus rhythm. Spontaneous diastolic depolarization was still present but was modulated by electrotonic depolarizations due to intranodal conduction block of atrial fibrillatory impulses. Incidentally, phase 4 depolarization resulted in the generation of spontaneous action potentials in the sinus node. However, the high activation rate in the sinoatrial border during atrial fibrillation prevented these spontaneous impulses to exit from the sinus node. Because of the minimal degree of sinus node overdrive suppression (9%) and the presence of concealed automaticity during atrial fibrillation, spontaneous termination of atrial fibrillation was promptly followed by resumption of normal sinus rhythm.

CONCLUSIONS
During atrial fibrillation, sinus automaticity still is present in the center of the sinus node and hardly overdrive suppressed due to a high degree of sinoatrial entrance block.
Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning.
Authors: Auchampach J A , Maruyama M , Cavero I , Gross G J 
Published: June 2012

BACKGROUND
Several recent studies suggest that activation of ATP-dependent potassium (K(ATP)) channels in the myocardium plays an important cardioprotective role during ischemia. The present study was undertaken to examine further the role of this ion channel in vivo in a model of "stunned" myocardium.

METHODS AND RESULTS
Barbital-anesthetized dogs were subjected to 15 minutes of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. Regional myocardial blood flow was measured by radioactive microspheres and segment function by sonomicrometry. Intravenous administration of the potassium channel opener aprikalim (RP 52891) at a dose that produced no significant systemic hemodynamic effects (10 micrograms/kg plus 0.1 microgram/kg/min) resulted in a marked improvement in segment shortening in the ischemic/reperfused myocardium compared with control animals (p less than 0.05) when given before the ischemic insult. However, administration of aprikalim immediately before reperfusion had no beneficial effect. Furthermore, pretreatment with the K(ATP) channel antagonist glibenclamide antagonized the recovery of contractile function afforded by aprikalim when administered at a low dose (0.3 mg/kg) that alone had no effect on postischemic recovery. In contrast, pretreatment with either a higher dose of glibenclamide (1.0 mg/kg) or the related sulfonylurea K(ATP) channel antagonist tolbutamide (100 mg/kg) resulted in a worsening of segment function after reperfusion. The ability of aprikalim and the K(ATP) channel antagonists to alter postischemic wall function occurred independently of differences in systemic hemodynamics, area at risk, and collateral blood flow during occlusion, the major determinants of the extent of myocardial stunning.

CONCLUSIONS
These results suggest that opening myocardial K(ATP) channels in the ischemic heart results in a marked cardioprotective effect in stunned myocardium and that these channels may serve an endogenous function, which is to provide protection from ischemic insults.
Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu----Val mutation and a 403Arg----Gln mutation.
Authors: Epstein N D , Cohn G M , Cyran F , Fananapazir L 
Published: June 2012

BACKGROUND
The disease gene for hypertrophic cardiomyopathy (HCM) has been identified as the beta-myosin heavy chain (beta-MHC) gene in some HCM families. We describe extensive clinical evaluations in two kindreds with two distinct point mutations in the beta-MHC gene.

METHODS AND RESULTS
We used single-strand confirmation polymorphism (SSCP) gel analysis of polymerase chain reaction-amplified products capturing each of the 40 beta-MHC gene exons to identify distinct missense mutations in two HCM kindreds. Clinical, ECG, and echocardiographic studies were performed in the two kindreds: kindred 2755 with amino acid 908Leu----Val mutation and kindred 2002 with amino acid 403Arg----Gln mutation. The morphological appearances of HCM were similar in these two kindreds. However, the two kindreds differed with respect to disease penetrance, age of onset of disease, and incidence of premature sudden death. Twelve of 31 adults (greater than or equal to 17 years) with the disease gene in kindred 2755 did not have left ventricular hypertrophy (LVH), and only five of these had ECG abnormalities. Thus, the disease penetrance in adults with this mutation was only 61%. None of 11 children aged less than 16 years had LVH. The 908 mutation was associated with a low incidence of cardiac events: Only two sudden deaths and one syncope occurred in 46 individuals with the mutant allele. In contrast, LVH was present in all 11 adults in kindred 2002 with the 403 mutation (100% disease penetrance). In addition, three of four affected children were symptomatic and had clinical evidence of HCM. The disease in this kindred was severe and resulted in six premature sudden deaths. Seven additional patients had syncope or presyncope.

CONCLUSIONS
In some kindreds, the HCM disease gene is more prevalent than indicated by echocardiography and ECG. Some point mutations may be associated with a more malignant prognosis. Preclinical identification of children with mutations associated with a high incidence of sudden death and syncope provides the opportunity to evaluate efficacy of early therapeutic interventions.
Effects of traditional coronary risk factors on rates of incident coronary events in a low-risk population. The Adventist Health Study.
Authors: Fraser G E , Strahan T M , Sabaté J , Beeson W L , Kissinger D 
Published: June 2012

BACKGROUND
California Seventh-Day Adventists have lower mortality rates from coronary heart disease (CHD) than other Californians. Associations between traditional risk factor and CHD events have not been reported previously for Adventists.

METHODS AND RESULTS
A cohort study allowed 6 years of follow-up of 27,658 male and female California Seventh-Day Adventists. Data collected included age, sex, physician-diagnosed hypertension and diabetes mellitus, body height, weight, previous and current cigarette smoking habits, and current exercise habits. Incident cases of definite myocardial infarction (MI) and definite fatal CHD were diagnosed according to recognized criteria. Both stratified and proportional hazards analyses demonstrated that in this low-risk population, the above traditional coronary risk factors exhibit their usual associations with risk of CHD events. It was noted that exercise had a strong negative association with fatal CHD events (relative risks [RR], 1.0, 0.66, and 0.50 with increasing exercise) but no association with risk of MI (either nonfatal or all cases). Conversely, obesity was much more clearly associated with MI (RR, 1.0, 1.18, and 1.83 with increasing tertiles of obesity) than with fatal events. The importance of the risk factors was similar in both sexes, except that the effect of cigarette smoking seemed more pronounced in women.

CONCLUSIONS
The epidemiology of coronary heart disease in this low-risk California population appears to be at least qualitatively similar to that seen in other groups. There was evidence that the effects of exercise and obesity may differ depending on whether fatal CHD and MI (either all MI or nonfatal alone) is the end point.
Thrombus regression in deep venous thrombosis. Quantification of spontaneous thrombolysis with duplex scanning.
Authors: van Ramshorst B , van Bemmelen P S , Hoeneveld H , Faber J A , Eikelboom B C 
Published: June 2012

BACKGROUND
Thrombus regression in heparin-treated, acute deep venous thrombosis of the lower extremity is poorly documented in the literature; different rates of thrombus resolution and recanalization are reported.

METHODS AND RESULTS
In a prospective follow-up study, duplex scanning was used to evaluate the thrombus regression in patients with documented acute femoropopliteal thrombosis. Eighty vein segments in 20 legs of 18 patients were subjected to repeat duplex scans at 1, 3, 6, 12, and 26 weeks after diagnosis; 49 segments showed thrombus at diagnosis. The popliteal vein showed the highest thrombus load at diagnosis, followed in descending order by the superficial femoral, profunda femoris, and common femoral vein segments (p less than 0.001). Thrombus regression was significant (p less than 0.001) in all segments and proceeded at an exponential rate that was equal in the different vein segments of the upper leg. Both thrombus resolution and recanalization appeared to be a function of the initial thrombus load and could not be related to individual vein segments. Recanalization was seen in 23 of 31 initially occluded segments and occurred within the first 6 weeks after diagnosis in 20 of 23 segments. Extension of thrombus despite anticoagulant therapy was observed in 15 vein segments and was not related to the initial thrombosis score (p = 0.1) or individual vein segments (p = 0.23). Thrombus extension in seven patients with prethrombotic conditions was not different (p = 0.9) from the other patients.

CONCLUSIONS
Duplex scanning is an important noninvasive tool to quantify thrombus regression in acute deep venous thrombosis in detail without unnecessary discomfort to the patient.