bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for the association of unexplained pulmonary hypertension in children with the major histocompatibility complex.
Authors: Barst R J , Flaster E R , Menon A , Fotino M , Morse J H
Published: June 2012

BACKGROUND

A link between primary pulmonary hypertension (PPH) and autoimmune disorders has been postulated. To investigate this relation, we performed immunofluorescent antinuclear antibody tests (ANA) and serological human leukocyte antigen (HLA)-A, B, C, DR, and DQ typing on two groups of Caucasian children with unexplained pulmonary hypertension (PHT) and their parents.

METHODS AND RESULTS

Group 1 consisted of 17 children with PPH including two patients with familial PPH and three patients with trivial congenital pulmonary to systemic communications. Group 2 consisted of 13 children with advanced PHT and anatomically large congenital pulmonary to systemic communications (PHT + shunt). Both groups had comparably severe pulmonary vascular disease documented by cardiac catheterization. The following statistically significant data (p less than 0.05) were obtained when the study groups were compared with those published for normal controls. Although positive ANAs and varying titers of autoantibodies were found in both groups of children and mothers (not fathers), +ANAs were only significant for the maternal groups. The PPH (group 1) children had increased frequencies of HLA-DR3, DRw52, and DQw2 and decreased DR5, whereas the group 2 (PHT + shunt) children (also their parents) had no statistically significant alterations in any of the DR or DQ alleles. The PPH mothers had decreased DQw3, an allele in linkage disequilibrium with DR5.

CONCLUSIONS

These immunogenetic data suggest that childhood PPH appears to be associated with the major histocompatibility complex alleles HLA-DR3, DRw52, and DQw2. This newly found correlation of juvenile PPH with these alleles adds this disease to the DR3+ group of autoimmune diseases. Further studies are needed to determine whether there is also an immunological or autoimmune component in some children with PHT + shunt lesions because this group lacked an HLA association.
Imaging of thrombi with tissue-type plasminogen activator rendered enzymatically inactive and conjugated to a residualizing label.
Authors: Ord J M , Hasapes J , Daugherty A , Thorpe S R , Bergmann S R , Sobel B E
Published: June 2012

BACKGROUND

Contemporary cardiovascular practice relies increasingly on thrombolysis as a therapeutic modality. Its optimal use requires prompt, noninvasive delineation of thrombotic occlusion in arterial beds and rapid detection of reocclusion after initially successful thrombolysis.

METHODS AND RESULTS

We have been developing an approach to noninvasively image thrombi in which plasminogen-activating properties of tissue-type plasminogen activator (t-PA) are attenuated by treatment with D-Phe-L-Pro-L-Arg-chloromethyl ketone (PPACK) and have shown that the inactive t-PA avidly and promptly binds to clots in vitro. In the present study, we conjugated this material to a residualizing label, radioiodinated dilactitol tyramine (*I-DLT), and characterized the potential use of the inactivated, conjugated t-PA as a radiopharmaceutical for imaging thrombi in vivo. The approach developed requires not only avid binding of the tracer to thrombi but also rapid clearance from plasma and a lack of prompt release of radiolabeled degradation products from the liver. The rapid clearance of unaltered or PPACK-treated t-PA was not influenced by conjugation to *I-DLT, but the release of radioiodinated degradation products into plasma after injection of *I-DLT-conjugated t-PA was markedly less than release of degradation products of directly radioiodinated t-PA. When 131I-DLT-PPACK-t-PA was infused for 15 minutes intravenously after a bolus injection of 20% in dogs with coronary, pulmonary, or carotid artery thrombi, clearance was rapid. Mean +/- SEM thrombus-to-blood ratios of radioactivity were high, ranging from 37 +/- 9:1 and 2.8 +/- 0.6:1 with carotid thrombi formed concomitantly or approximately 30 minutes before infusion of tracer, respectively, to 35:1 for concomitantly formed coronary thrombi, 42 +/- 7:1 and 8.1 +/- 0.8:1 for concomitantly formed and preformed pulmonary thrombi, respectively, and 18:1 for a preformed femoral artery thrombus. Thrombi were detectable by planar gamma scintigraphy even though image quality was affected adversely by low concentrations of radioactivity that in aggregate composed a relatively large amount of radioactivity in underlying and overlying tissues. This limitation was overcome by tomographic imaging, which was used to detect both femoral and pulmonary thrombi.

CONCLUSIONS

Use of enzymatically inactivated t-PA coupled to a residualizing label permits rapid detection and localization of thrombi in vivo.
Color Doppler regurgitant characteristics of normal mechanical mitral valve prostheses in vitro.
Authors: Baumgartner H , Khan S , DeRobertis M , Czer L , Maurer G
Published: June 2012

BACKGROUND

To evaluate normal regurgitant characteristics of St. Jude (SJ) and Medtronic-Hall (MH) mitral valves, four sizes (25-31 mm) of each were studied in a pulsatile flow model.

METHODS AND RESULTS

Regurgitant flow was measured by flowmeter at left ventricular pressures of 80, 130, and 180 mm Hg. Peak regurgitant flow rates ranged from 6.2 to 12.7 cm3/sec in SJ valves and from 7.9 to 17.5 cm3/sec in MH valves. Regurgitant orifice areas calculated from the Doppler continuity equation ranged from 1.6 to 2.0 mm2 in SJ valves and from 2.2 to 2.9 mm2 in MH valves. Regurgitant volumes across the closed valve at a left ventricular pressure of 130 mm Hg were normalized to an ejection time of 280 msec and ranged from 1.5 to 1.9 cm3 in SJ valves and from 2.1 to 2.8 cm3 in MH valves. Jets were imaged by color Doppler in six rotational planes, and jet size and morphology were compared with those of regurgitant jets from circular orifices with sizes comparable to the calculated prosthetic valve regurgitant orifices (1.1-3.1 mm2). SJ valves showed two converging jets from the pivot points, one central jet, and a variable number of peripheral jets. The mean color jet area derived from the six image planes ranged from 1.6 to 5.3 cm2. Aliasing occurred only close to the valve (maximal distance 0.5-2.0 cm). MH valves showed a large central jet with a maximal length of aliased flow between 2.0 and 5.5 cm. Depending on valve size, driving pressure, and image plane, one or two small peripheral jets were found. These jets did not show aliasing in any case. The mean color jet area ranged from 5.1 to 11.0 cm2. Jets originating from circular orifices of comparable size showed jet areas from 5.5 to 13.9 cm2 and aliasing distances from 3.3 to 7.3 cm. At similar regurgitant orifice areas, driving pressures, and regurgitant flows, the measured color areas and aliasing distances were smallest in SJ valves, larger in MH valves, and largest in simple circular orifices.

CONCLUSIONS

Large, complex regurgitant jets can be found in normal closed SJ and MH valves by color Doppler, although regurgitant flow volume is minimal. Jet size and velocity distribution differs markedly between SJ valves, MH valves, and circular orifices, even with comparable driving pressure, regurgitant orifice area, and regurgitant volume. The characteristic patterns of normal regurgitation must be recognized to avoid incorrect diagnoses of pathological regurgitation in SJ and MH prosthetic valves. MH valves should not be removed solely on the basis of a central regurgitant jet with a long aliasing distance. Peripheral jets in MH valves and all jets in SJ valves should be considered normal as long as no or only minimal aliasing is present. In contrast, peripheral jets with significant aliasing may represent strong evidence of pathological regurgitation.
Complications and validity of pulmonary angiography in acute pulmonary embolism.
Authors: Stein P D , Athanasoulis C , Alavi A , Greenspan R H , Hales C A , Saltzman H A , Vreim C E , Terrin M L , Weg J G
Published: June 2012

BACKGROUND

The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED:

METHODS AND RESULTS

Complications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p less than 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years (p less than 0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%.

CONCLUSIONS

The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk.
Elevated endothelin-1 in heart failure and loss of normal response to postural change.
Authors: Stewart D J , Cernacek P , Costello K B , Rouleau J L
Published: June 2012

BACKGROUND

The possible contribution of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, to neurohumoral compensation for hemodynamic stress was examined in nine normal volunteers and six patients with severe congestive heart failure.

METHODS AND RESULTS

Plasma levels of endothelin-1 were measured with a sensitive and specific radioimmunoassay. Venous blood samples were obtained after 90 minutes of supine rest and serially during 30 minutes of 60 degrees upright tilt. Endothelin-1 levels were compared with those of known neurohumoral mediators of compensation. In normal subjects, the resting levels of endothelin-1 were low (0.74 +/- 0.11 pg/ml), and there was a rapid increase to 1.37 +/- 0.07 pg/ml at 5 minutes of upright tilting (p less than 0.05). This increase was not sustained at 10 and 15 minutes of tilt, but there was a trend toward a second rise at 30 minutes (1.14 +/- 0.17 pg/ml; p = 0.06). This biphasic pattern of response was shared by dopamine and reflected the response of systemic blood pressure to postural change. In contrast, slower and more sustained increases in circulating levels were observed for norepinephrine, epinephrine, aldosterone, plasma renin activity, and vasopressin, whereas atrial natriuretic peptide tended to decrease progressively. Patients with congestive heart failure had markedly higher basal levels of circulating endothelin-1 than normal subjects (3.7 +/- 0.5 pg/ml; p less than 0.01), and there was no further increase on postural change. Similar patterns were observed for the other neurohumoral mediators measured, with the degree of blunting of the response to upright tilting in heart failure being inversely related to the magnitude of increase in basal levels.

CONCLUSIONS

Alterations in plasma levels of endothelin in congestive heart failure and in response to postural change were qualitatively and quantitatively similar to the alterations of known mediators of neurohumoral compensation. In addition, the increase in plasma endothelin-1 during upright tilting in normal subjects preceded the increases in circulating levels of the other vasoconstrictor mediators, consistent with a role of endothelin-1 in neurohumoral compensation for hemodynamic stress.
Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy.
Authors: Leclerc G , Isner J M , Kearney M , Simons M , Safian R D , Baim D S , Weir L
Published: June 2012

BACKGROUND

Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile phenotype) preferentially express smooth muscle myosin, proliferating smooth muscle cells (synthetic phenotype) have been shown to preferentially express nonmuscle myosin in vitro. Accordingly, we analyzed the expression of a recently cloned isoform of human nonmuscle myosin heavy chain (MHC-B) in fresh human restenotic lesions.

METHODS AND RESULTS

A total of 10 lesions, including four restenosis (three superficial femoral arterial lesions and one saphenous vein bypass lesion) and six primary (four superficial femoral arterial lesions and two coronary arterial lesions) obtained percutaneously by directional atherectomy, were processed for examination by in situ hybridization. In total, 150 tissue sections of restenotic lesions (66 sections), primary lesions (78 sections), and normal internal mammary artery (six sections) were hybridized with the nonmuscle MHC-B probe. Restenotic lesions showed intense hybridization to the nonmuscle MHC-B cRNA probe, as demonstrated by a clustering of more than 20 grains per cell nucleus in 80% of the cells examined within a high-power field (x250); in contrast, an equivalent degree of hybridization was observed in only 7% of cells within primary lesions (p less than 0.001). Results of immunocytochemistry using monoclonal antibody to smooth muscle actin indicated that cells demonstrating strong hybridization were smooth muscle in origin.

CONCLUSIONS

These findings demonstrate that 1) human vascular tissue obtained by percutaneous directional atherectomy constitutes appropriate biopsy material for gene expression studies at the mRNA level, and 2) nonmuscle MHC-B mRNA is present in greater abundance among restenotic versus primary vascular stenoses. These observations thus provide a rational basis to explore restenotic lesions on a larger scale to identify genes that are activated in these lesions and establish potential targets for future gene therapy.
Prevalence, circumstances, mechanisms, and risk stratification of sudden cardiac death in unipolar single-chamber ventricular pacing.
Authors: Zehender M , Büchner C , Meinertz T , Just H
Published: June 2012

BACKGROUND

Permanent cardiac pacing is well established for the improvement of prognosis and quality of life in patients with severe bradycardia. However, sudden cardiac death still remains an unresolved problem, as it occurs in approximately 20-30% of paced patients. This 2-year follow-up study was directed at prospectively assessing prevalence, circumstances, and mechanisms of sudden death in 2,021 permanently paced patients.

METHODS AND RESULTS

During the observation period, 220 patients (11%) died (mean pacing interval, 50.5 +/- 7 months). Lethal cerebrovascular events in 66 of 220 patients (30%) and sudden death in 49 of 220 patients (23%) were the two most frequently reported modes of death. Nonsudden (first year, 20%; subsequent years, 6.9%; p less than 0.01) and sudden death mortality rate (4% versus 1.8%, p less than 0.05) were highest during the first year. Mortality was unrelated to the patient's activity status at the time of death. Sudden cardiac death occurred more often in male patients (increased risk, 1.7 versus female patients; p less than 0.001) and patients younger than 60 years of age (5.2 versus patients older than 60 years, p less than 0.001). Patients with severe bradycardia (sudden death rate, 28%), severe atrioventricular block (25%), or atrial fibrillation with low ventricular rate (25%) before pacemaker implantation were more likely to suffer from sudden cardiac death than patients with previous syncopal attacks (sudden death rate, 15%) or sick sinus syndrome (17%). The highest incidence of sudden death was observed in patients with bifascicular and trifascicular bundle branch block. In this group, 35% of patients died suddenly during the follow-up period compared with 18% of patients without bundle branch block. In a subsequent study in 90 consecutive patients with various types of bundle branch block, undersensing of up to 13% of ectopic ventricular beats occurred in patients with bifascicular block. Pacing-induced tachyarrhythmias and ventricular fibrillation were documented in 10% of undersensed ectopic ventricular beats as well as in the setting of atrial fibrillation associated with ventricular arrhythmias.

CONCLUSIONS

Young age, male sex, and a severely diseased heart indicated by the presence of bifascicular and trifascicular bundle branch block are the strongest predictive clinical parameters for sudden cardiac death, especially in the first year after pacemaker implantation.
Myocardial adrenergic denervation supersensitivity depends on a postreceptor mechanism not linked with increased cAMP production.
Authors: Hammond H K , Roth D A , Ford C E , Stamnas G W , Ziegler M G , Ennis C
Published: June 2012

BACKGROUND

Two major hypotheses have been proposed to explain catecholamine supersensitivity after myocardial denervation, but neither sufficiently explains certain features of the phenomenon. In addition, a nonsurgical method for long-term myocardial adrenergic denervation is desirable but has not been accomplished or described with respect to catecholamine supersensitivity.

METHODS AND RESULTS

We have accomplished chronic myocardial adrenergic denervation by using 6-hydroxydopamine (6-OHDA). Sixteen weeks after 6-OHDA administration to newborn pigs, we found substantial myocardial adrenergic denervation associated with beta-adrenergic receptor (beta AR) downregulation. Despite decreased beta AR number, the dose of isoproterenol yielding 50% maximal heart rate change (ED50) was decreased, and heart rates during exercise showed increased responsiveness despite decreased circulating catecholamines. Thus, stimulation of fewer receptors yielded an increased response, implying improved signal transduction efficiency. Competitive binding studies with isoproterenol showed an increased proportion of beta AR with high-affinity binding in myocardial membranes from 6-OHDA pigs, suggesting that interaction between beta AR and cardiac G, may contribute to improved signal transduction efficiency. However, measures of adenylyl cyclase activity indicated marked reduction in beta AR-dependent and G2-dependent cAMP production in myocardial membranes from denervated animals despite a normal amount of cardiac Gs and decreased Gi.

CONCLUSIONS

We have demonstrated that substantial, long-term myocardial adrenergic denervation is possible using 6-OHDA. Denervation supersensitivity in this model does not depend on enhanced cAMP stimulation but rather depends on postreceptor elements in the beta AR-responsive pathway that may be independent of Gs-activated adenylyl cyclase activity. In this model of adrenergic denervation supersensitivity, beta-receptors, through Gs, may be linked to an alternative effector that drives heart rate responsiveness.
High-current stimuli to the spared epicardium of a large infarct induce ventricular tachycardia.
Authors: Kavanagh K M , Kabas J S , Rollins D L , Melnick S B , Smith W M , Ideker R E
Published: June 2012

BACKGROUND

Previous studies have demonstrated that both ventricular tachycardia (VT) and ventricular fibrillation (VF) may begin as figure-eight reentry: VT with a longer cycle length from spared tissue adjacent to an infarct by programmed stimulation and VF with a shorter cycle length from noninfarcted tissue by a large premature S2 stimulus. These results suggest that the type of tissue or cycle length of the arrhythmia rather than the mode of induction determines whether the figure eight becomes sustained VT or degenerates into VF. Thus, a protocol similar to that by which a VF threshold is determined may induce VT rather than VF when performed in the spared tissue over an infarct.

METHODS AND RESULTS

In 10 dogs, 4 days after occlusion-reperfusion of the left anterior descending coronary artery, 10 S1 stimuli were delivered from a total of 34 right and left ventricular sites outside the infarct. An epicardial S2 stimulus over the infarct was increased in 10-mA steps and introduced in diastole at decreasing cycle lengths of 5 msec until VT or VF was induced. Sustained monomorphic figure-eight VT was induced from 24 S1 sites and VF from nine (p = 0.03). The mean cycle lengths for the initial six arrhythmic cycles was 152 +/- 33 msec for VT and 115 +/- 13 msec for VF (p less than 0.001). Mean transmural infarct extent was 80% in five dogs with only VT, 63% in three dogs with both VT and VF, and 15% in two dogs with only VF. Different morphologies of VT were induced by changing the S1 site, the S2 strength, or the S1S2 coupling interval. In 25 of the 34 arrhythmias, the central part of the initial figure-eight pathway was oriented opposite the S1 activation sequence in that region.

CONCLUSIONS

A large S2 stimulus over a nontransmural infarct induces VT if the spared myocardium is thin. This study introduces a useful technique for inducing sustained monomorphic VT in which the location and direction of the figure-eight pathway are known a priori and in which different morphologies of sustained VT can be produced by changing the S1 site.
Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter.
Authors: Flugelman M Y , Jaklitsch M T , Newman K D , Casscells W , Bratthauer G L , Dichek D A
Published: June 2012

BACKGROUND

Gene transfer into the arterial wall may provide a novel therapeutic strategy for the treatment of coronary artery restenosis. Previously described methods for gene transfer into the arterial wall require total vessel occlusion for 30 minutes. We sought to develop a protocol for gene transfer within a more clinically relevant time frame.

METHODS AND RESULTS

We used a perforated balloon (Wolinsky) catheter to inject retroviral vector-containing virions into rabbit aortas in vivo. The virions were injected within 1 minute. Aortas were removed 5-14 days after injection and analyzed for evidence of gene transfer. In initial studies, nine rabbits were injected with a vector expressing the beta-galactosidase gene, and nine rabbits were injected with either non-beta-galactosidase-containing vectors or with a vehicle control. Histochemical staining of aortic tissues revealed blue (positive) cells in eight of nine experimental rabbits and six of nine controls. Because of the lack of specificity of the beta-galactosidase detection system, we adopted a polymerase chain reaction-based protocol in which oligonucleotide primers were used to amplify specific vector-related sequences from aortic tissue extracts. The polymerase chain reaction protocol, calibrated with standards containing known numbers of transduced cells, revealed low amounts of vector-related sequences in six of 12 vector-injected rabbits and in one of 13 controls (p less than 0.03). Comparison with standards indicated that fewer than 100 transduced cells were present in a 2-cm length of the injected aortic tissue.

CONCLUSIONS

Although in vivo gene transfer through an infusion balloon catheter can be accomplished within 1 minute, the therapeutic use of this protocol is limited by the small number of cells that are transduced.
Recent insights into coronary collateral circulation.
Authors: Sasayama S , Fujita M
Published: June 2012

The functional significance of coronary collaterals in humans has been debated for many years. Correlations have now been made between the anatomic appearance of coronary collateral vessels visualized at the time of intracoronary thrombolytic therapy during the acute phase of myocardial infarction and the creatine kinase time--activity curve, infarct size, and aneurysm formation. These studies demonstrate a protective role of collaterals in hearts with coronary obstructive disease, showing smaller infarcts, less aneurysm formation, and improved ventricular function compared with patients in whom collaterals were not visualized. There is ample evidence that collaterals respond to myocardial ischemia by opening preexistent channels. When the cardiac myocyte is rendered ischemic, collaterals develop actively by growth with DNA replication and mitosis of endothelial and smooth muscle cells. Heparin-binding growth factors are present in the heart, but their biological activity is quiescent under normal physiological conditions. Once ischemia develops, these factors are activated and become available for receptor occupation, which may initiate angiogenesis after exposure to exogenous heparin. This characteristic of heparin to potentiate the mitogenic activity of acidic fibroblast growth factor has recently been used in the clinical setting as a possible therapeutic modality in patients with coronary artery disease. Patients performing 20 rounds of exercise serially after receiving intravenous injection of heparin showed significantly greater increases in exercise capacity and improvement of clinical symptoms compared with the control group who performed the same exercise without heparin. Further study of neovascularization may lead to a new therapeutic strategy for ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Success, safety, and late electrophysiological outcome of low-energy direct-current ablation in patients with the Wolff-Parkinson-White syndrome.
Authors: Lemery R , Talajic M , Roy D , Coutu B , Lavoie L , Lavallée E , Cartier R
Published: June 2012

BACKGROUND

Percutaneous ablation of accessory pathways with the use of a defibrillator can be accomplished with high-energy direct-current (DC) shocks of 150-400 J, but complications include cardiac tamponade and sudden cardiac death, mostly resulting from significant electrical arcing and barotrauma. A new low-energy DC power source with a brief time-constant capacitive discharge delivers shocks of 2-40 J and eliminates or greatly reduces arcing. This report describes our initial experience with this device in 60 consecutive patients (mean age, 34 years; range, 9-67 years) with Wolff-Parkinson-White syndrome. Accessory pathways were located in the left free wall in 36 patients, in the right free wall in two, were posteroseptal in 18, and anteroseptal in four. Most patients (77%) had their initial diagnostic electrophysiological study and catheter ablation during the same session.

METHODS AND RESULTS

Selective ablation of accessory pathways was successful in 55 patients (92%). The mean cumulative energy was 312 +/- 284 J and the mean creatine kinase MB peak (normal, 0-30 units) was 42 +/- 27 units. Patients with left free wall accessory pathways required less procedure time for ablation (2.7 +/- 0.8 versus 3.6 +/- 1.5 hours, p less than 0.0007) and less fluoroscopy time (46 +/- 24 versus 66 +/- 33 minutes, p less than 0.002). Complications were limited to transient pericarditis (three patients), one iliac artery dissection, and cardiac tamponade probably caused by catheter repositioning in the coronary sinus (one patient). An electrophysiological study was repeated in 50 of the 55 successful cases at a mean of 9 +/- 5 months. This study was normal in 48 of 50 (96%) patients.

CONCLUSIONS

Low-energy DC ablation is safe and effective treatment for accessory pathways in children and adults. The long-term outcome is excellent as documented by electrophysiological restudy.
Regression of coronary artery dimensions after successful aortic valve replacement.
Authors: Villari B , Hess O M , Meier C , Pucillo A , Gaglione A , Turina M , Krayenbuehl H P
Published: June 2012

BACKGROUND

The effect of regression of myocardial hypertrophy on coronary artery dimensions was evaluated in patients with aortic valve disease who underwent valve replacement.

METHODS AND RESULTS

Cross-sectional area (CSA) of the three major coronary arteries (left anterior descending [LAD], left circumflex [LCx], and right coronary artery) was determined by quantitative coronary arteriography in 15 patients with aortic valve disease before and 38 months (range, 14-113 months) after successful aortic valve replacement. Twelve normal subjects served as controls. Left ventricular (LV) angiographic mass was calculated according to the method of Rackley. CSA of the left coronary artery was larger in aortic valve disease than in controls (LAD, 15 versus 8 mm2, p less than 0.001; LCx, 14 versus 6 mm2, p less than 0.001). After valve replacement, CSA of the left coronary artery decreased (LAD, 12 mm2, p less than 0.05 versus before surgery; LCx, 11 mm2, p less than 0.05 versus before surgery) but remained significantly larger than in controls. CSA of the right coronary artery in patients with aortic valve disease was not different from controls. LV muscle mass was significantly increased in aortic valve disease patients before (364 g) and after (250 g) valve replacement compared with controls (135 g). The appropriateness of coronary artery size with respect to muscle mass was evaluated by normalizing CSA of the left coronary artery (LAD + LCx) per 100 g of LV muscle mass (mm2/100 g). This index amounted to 11 mm2/100 g in controls, to 8 mm2/100 g in preoperative patients (p less than 0.05 versus controls), and to 10 mm2/100 g in postoperative patients with aortic valve disease (p = NS versus controls).

CONCLUSIONS

In patients with aortic valve disease, CSA of the proximal LAD and LCx is increased, but this increase is not sufficient to keep CSA per 100 g of LV mass within normal limits. The postoperative decrease in muscle mass is associated with a decrease in the size of LAD and LCx, whereas the size of the right coronary artery remains unchanged. In contrast to the preoperative state, the residually hypertrophied LV myocardium after aortic valve replacement is supplied by an enlarged but adequately sized LAD and LCx.
Relation of plasma lipid and apoprotein levels to progressive intimal hyperplasia after arterial endarterectomy.
Authors: Colyvas N , Rapp J H , Phillips N R , Stoney R , Perez S , Kane J P , Havel R J
Published: June 2012

BACKGROUND

To examine the relation of plasma lipoproteins to the proliferative response after arterial injury in humans, we examined the plasma lipid, lipoprotein, and apoprotein levels of 20 patients with early recurrent stenosis caused by intimal hyperplasia after carotid endarterectomy. These were compared with 20 controls who had no evidence of recurrent stenosis by duplex ultrasound scanning.

METHODS AND RESULTS

By univariate analysis, the reoperated patients had higher levels of plasma cholesterol (251 versus 225 mg/dl, p less than 0.05), total triglycerides (173 versus 105 mg/dl, p less than 0.03), and low density lipoprotein (LDL) apoprotein B (99.8 versus 77.2 mg/dl, p less than 0.003). The ratio of cholesterol to apoprotein B in LDL was lower in patients with restenosis (p less than 0.04), suggesting LDL of smaller diameter. High density lipoprotein (HDL) cholesterol level was reduced (45 versus 55 mg/dl, p less than 0.01) in patients with restenosis. With statistical adjustment for the correlations between these variables by multivariate analysis, both LDL apoprotein B and HDL cholesterol were independent predictors of the risk of restenosis. Ten patients with restenosis but only two controls had one or two apolipoprotein E4 alleles.

CONCLUSIONS

Elevated lipid levels usually associated with an increased risk of atherosclerosis may predispose patients to an increased incidence of intimal hyperplasia after endarterectomy.
Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins.
Authors: Shear C L , Franklin F A , Stinnett S , Hurley D P , Bradford R H , Chremos A N , Nash D T , Langendorfer A
Published: June 2012

BACKGROUND

Lovastatin produces consistent dose-related reductions in plasma levels of low density lipoprotein (LDL) cholesterol along with variable decreases in triglycerides and increases in high density lipoprotein (HDL) cholesterol. Patient characteristics from the Expanded Clinical Evaluation of Lovastatin (EXCEL) study were examined to determine their association with the magnitude of lovastatin-induced changes in these lipids and lipoproteins.

METHODS AND RESULTS

After a baseline period consisting of dietary therapy, 8,245 patients with moderate hypercholesterolemia were randomized to five groups that received 48 weeks of treatment with either placebo or daily doses of lovastatin ranging from 20 to 80 mg. By use of linear statistical models, 20 different patient characteristics were examined for modification of the dose-dependent responses observed. For LDL cholesterol, the following were associated with enhanced lowering (p less than 0.05; percent changes are placebo-corrected, adjusted mean changes from baseline for the 80-mg/day lovastatin group): full drug compliance (-41.9%) versus 80% compliance (-20.3%); an age of 65 (-43.4%) versus 45 years (-38.1%) for women; white race (-40.9%) versus black race (-38.0%); and 4.5-kg weight gain (-42.6%) versus 4.5-kg weight loss (-37.9%). Similar relations for enhanced triglyceride lowering were found with older age and weight gain. Patients with initially low HDL cholesterol (less than 0.91 mmol/l) and high triglycerides (greater than 2.26 mmol/l) had enhanced responses for these parameters: placebo-corrected percent changes at 80 mg/day were -27.4% for triglycerides and +12.3% for HDL cholesterol.

CONCLUSIONS

Overall, patient characteristics had very little impact of clinical importance on the dose-dependent LDL cholesterol lowering found with lovastatin. In patients with initially high levels of triglycerides and low levels of HDL cholesterol, the elevation of HDL cholesterol produced by lovastatin appears to be enhanced.
Continuous measurement of left ventricular performance during and after maximal isometric deadlift exercise.
Authors: Sullivan J , Hanson P , Rahko P S , Folts J D
Published: June 2012

BACKGROUND

Isometric exercise produces a reflex increase in arterial blood pressure that is proportional to the intensity and mass of muscle used during contraction. Little is known about the transient effects of heavy weight lifting on left ventricular performance. In this study, we measured continuous changes in left ventricular performance during maximal large-muscle isometric exercise using the standing deadlift position.

METHODS AND RESULTS

Ten healthy young men performed serial deadlifts at 50% of maximal voluntary effort for 90 seconds and 100% of maximal effort for 30 seconds. Echocardiographic imaging (apical four-chamber view), arterial blood pressure (brachial artery catheter), and electrocardiographic monitoring were recorded throughout the deadlift and for 30 seconds of recovery. Aortic flow velocity was also monitored during a separate series of deadlifts. During 100% maximal deadlift, mean arterial pressure increased from 108 +/- 4 to 164 +/- 6 mm Hg. Left ventricular ejection fraction declined initially (from 57 +/- 2% to 49 +/- 3%) at 15 seconds into the lift and recovered (56 +/- 1%) due to significant increases in end-diastolic volume (104 +/- 11 ml to 132 +/- 16 ml) by the end of the lift. The peak systolic pressure/end-systolic volume ratio did not change during the deadlift. After cessation of the deadlift, mean arterial pressure declined precipitously (to 88 +/- 4 mm Hg) within 5 seconds and gradually returned to baseline after 30 seconds. Left ventricular performance indexes all increased significantly during the recovery phase (ejection fraction to 68 +/- 3%, peak systolic pressure/end-systolic volume ratio to 5.9 +/- 0.9). Findings were qualitatively similar for the 50% deadlift.

CONCLUSIONS

During an intense isometric deadlift, left ventricular performance declines initially but is restored by the Frank-Starling mechanism. Upon release of the deadlift, increased left ventricular performance develops in conjunction with a rapid decrease in arterial pressure. The combined effects of increased wall stress during the lift phase and enhanced contractility during the release phase probably contribute to left ventricular hypertrophy associated with repetitive weight training.
Ultrafast computed tomography analysis of regional radius-to-wall thickness ratios in normal and volume-overloaded human left ventricle.
Authors: Feiring A J , Rumberger J A
Published: June 2012

BACKGROUND

This study tested two hypotheses: 1) regional left ventricular radius-to-wall thickness ratios (R/T) are uniform in normal subjects, and 2) patients with left ventricular hypertrophy secondary to compensated volume overload normalize global and regional R/T.

METHODS AND RESULTS

Ultrafast computed tomography was used to measure regional short-axis ventricular R/T in 11 normal subjects and 13 patients with compensated aortic insufficiency (AI) of moderate severity (regurgitant fraction, greater than or equal to 25%). Radius and wall thickness dimensions were calculated by two different methods. In method 1, the average radius and wall thickness were determined for each planimetric transaxial tomographic image. In method 2, the left ventricle was three-dimensionally reconstructed; then, new radii and wall thickness were recalculated as if all the images were acquired orthogonal to the endocardial surface at each tomographic level. In normals, the mean R/T ratio was 1.75 +/- 0.11 (SEM) with method 1 and 1.80 +/- 0.07 with method 2. The R/T ratios varied as a function of the relative apex-to-base position. R/T ratios at the basal four levels were relatively uniform, whereas R/T at the lower three tomographic levels were significantly less than those at the base (p less than 0.01). Patients with AI had a mean regurgitant fraction of 44 +/- 3.8% (range, 25-63%). The mean R/T ratio was 2.18 +/- 0.16 with method 1 and 2.55 +/- 0.18 with method 2. Similar to the pattern observed in normals, the regional R/T ratios at the lower three or four levels were significantly less than the basal R/T ratios (p less than 0.01). Regional comparison of the normal to the volume-overloaded ventricles demonstrated that R/T ratios in the AI patients were significantly greater at the upper five levels with method 1 and at all eight levels with method 2 (p less than 0.01-0.001, AI versus normal).

CONCLUSIONS

These findings demonstrate that regional R/T ratios are heterogeneous in both normals and patients with left ventricular hypertrophy secondary to compensated aortic insufficiency. Furthermore, these findings challenge the accepted hypothesis that global and regional R/T ratios normalize in patients with compensated volume-overload hypertrophy.
Effect of chronic rapid ventricular pacing on total vascular capacitance.
Authors: Ogilvie R I , Zborowska-Sluis D
Published: June 2012

BACKGROUND

Rapid right ventricular pacing (RRVP) at 250 bpm for 3-6 weeks produces chronic heart failure manifested by a reduction in cardiac output and increases in right atrial, pulmonary artery, and capillary wedge pressures.

METHODS AND RESULTS

One week after splenectomy and pacemaker placement, vascular capacitance, unstressed volume, and compliance were determined in 19 anesthetized dogs from pressure-volume curves using transient circulatory arrests induced by acetylcholine. Nine dogs were restudied 31 +/- 1 days later without RRVP, and 10 dogs underwent RRVP at 250 bpm and were restudied at 23 +/- 8 and 38 +/- 8 days in cardiac failure and after 1 and 2 weeks of postpacing recovery. Control animals had no changes in vascular capacitance or compliance. Dogs undergoing RRVP exhibited a marked increase in mean circulatory filling pressure (5.4 +/- 0.4 to 10.5 +/- 1.5 mm Hg) during the development of cardiac failure with a reduction in unstressed volume (81.9 +/- 5.7 to 43.9 +/- 8.1 ml.kg-1) without changing total vascular compliance. Total blood volume decreased (95.4 +/- 6.2 to 66.7 +/- 6.5 ml.kg-1) primarily due to a reduction in packed cell volume. The pressure gradient for venous return and overall venous resistance was unaltered. Central blood volume as a proportion of total blood volume increased (9.3 +/- 1.7% to 16.0 +/- 2.7%). Arterial compliance and capacity and pulmonary vascular compliance were reduced. In the 2-week postpacing period, except for a reduced cardiac response to a volume load, all of these parameters returned to baseline values.

CONCLUSIONS

Chronic RRVP induced cardiac failure with a marked reduction in total vascular capacitance due to a reduction in unstressed volume without altering compliance. The rise in mean circulatory filling pressure was limited by a reduction in total blood volume.
Selective radiofrequency ablation of the slow pathway for the treatment of atrioventricular nodal reentrant tachycardia. Evidence for involvement of perinodal myocardium within the reentrant circuit.
Authors: Kay G N , Epstein A E , Dailey S M , Plumb V J
Published: June 2012

BACKGROUND

The circuit of atrioventricular (AV) nodal reentrant tachycardia may include perinodal atrial myocardium. Furthermore, in patients with dual AV nodal pathways, the atrial insertion of the slow pathway is likely to be located near the ostium of the coronary sinus, caudal to the expected location of the AV node. The present study was designed to evaluate the safety and efficacy of selective catheter ablation of the slow pathway using radiofrequency energy applied along the tricuspid annulus near the coronary sinus ostium as definitive therapy for AV nodal reentrant tachycardia.

METHODS AND RESULTS

Among 34 consecutive patients who were prospectively enrolled in the study, the slow pathway was selectively ablated in 30, and the fast pathway was ablated in four. Antegrade conduction over the fast pathway remained intact in all 30 patients after successful selective slow pathway ablation. There was no statistically significant change in the atrio-His interval (68.5 +/- 21.8 msec before and 69.6 +/- 23.9 msec after ablation) or AV Wenckebach rate (167 +/- 27 beats per minute before and 178 +/- 50 beats per minute after ablation) after selective ablation of the slow pathway. However, the antegrade effective refractory period of the fast pathway decreased from 348 +/- 94 msec before ablation to 309 +/- 79 msec after selective slow pathway ablation (p = 0.005). Retrograde conduction remained intact in 26 of 30 patients after selective ablation of the slow pathway. The retrograde refractory period of the ventriculo-atrial conduction system was 285 +/- 55 msec before and 280 +/- 52 msec after slow pathway ablation in patients with intact retrograde conduction (p = NS). There were three complications in two patients, including an episode of pulmonary edema and the development of spontaneous AV Wenckebach block during sleep in one patient after slow pathway ablation and the late development of complete AV block in another patient after fast pathway ablation. Over a mean follow-up period of 322 +/- 73 days, AV nodal reentrant tachycardia recurred in three patients, all of whom were successfully treated in a second ablation session.

CONCLUSIONS

Radiofrequency ablation of the slow AV pathway is highly effective and is associated with a low rate of complications.
Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function.
Authors: Margossian S S , White H D , Caulfield J B , Norton P , Taylor S , Slayter H S
Published: June 2012

BACKGROUND

A number of parameters reflecting the effects of idiopathic dilated cardiomyopathy (IDC) on the structure and function of myosin from the human myocardium were analyzed.

METHODS AND RESULTS

The content of the regulatory light chain, LC2, was reduced in myopathic heart myosin in contrast to the controls in which it was present in stoichiometric amounts relative to the essential light chain, LC1. In IDC hearts, the absence or significant reduction in amount of LC2 was related to the presence of an active protease, which was isolated and purified about 130-fold. The protease exhibited a significant degree of specificity: It cleaved LC2 almost totally (but not the heavy chains) in human control heart myosin but only partially cleaved LC2 in canine heart or in rabbit skeletal muscle myosins. The protease was present at a very low level or was inactive in control heart tissue. When the LC1/LC2 molar ratio was calculated, it was found to be 1:1.0 in control heart myosin and remained constant in various samples analyzed, whereas in myopathic myosin from different individuals, this ratio varied from 1:0.1 to 1:0.69. The rates of ATP binding to control and myopathic myosins were similar, whereas the Vm of actin-activated ATPase of myopathic myosin was about 25% less than that of the control. However, ATP binding and its hydrolysis by control S1, i.e., the myosin head, were faster by a factor of 2 than that of the myopathic S1. In addition, control myosin synthetic thick filament length as well as turbidity in solution, measured by light scattering, were twice as large as those of the myopathic heart myosin. These effects induced by myopathy in both filament assembly and turbidity were reversed upon reassociation of IDC myosin with LC2.

CONCLUSIONS

The changes in myosin structure and function were linked to a protease-mediated cleavage of LC2 in myosin; a possible role for the protease in the degenerative effects of idiopathic dilated cardiomyopathy is thus defined.
Coronary calcification and its relation to extracoronary atherosclerosis in asymptomatic hypercholesterolemic men. The PCV METRA Group.
Authors: Megnien J L , Sene V , Jeannin S , Hernigou A , Plainfosse M C , Merli I , Atger V , Moatti N , Levenson J , Simon A
Published: June 2012

BACKGROUND

The prevalence of coronary calcifications and extracoronary plaques was studied in patients with asymptomatic hypercholesterolemia.

METHODS AND RESULTS

Ultrafast computed tomography for coronary calcification (presence or absence: calcium score) and echographic assessment of carotid, aortic, and femoral plaques were performed in 111 hypercholesterolemic men: 65% had coronary calcification, 72% had extracoronary plaque. The two lesions were associated as: 1) compared with subjects without coronary calcification, those with calcification had a higher prevalence of aortic (p less than 0.05) and femoral (p less than 0.01) plaque and of two diseased sites (p less than 0.05); 2) the prevalence of coronary calcification was higher in the presence than in the absence of aortic (p less than 0.05) or femoral (p less than 0.01) plaque and higher in two (p less than 0.01) and three diseased (p less than 0.05) sites than in no diseased site; 3) the calcium score was higher in the presence than in the absence of carotid (p less than 0.05), aortic (p less than 0.05), or femoral (p less than 0.001) plaque, higher in two (p less than 0.001) and three diseased (p less than 0.05) sites than in no diseased sites, and higher in two (p less than 0.01) than in one diseased site; and 4) the calcium score correlated with femoral plaque (p less than 0.001). Overall, the presence of two or three diseased extracoronary sites versus no or one diseased site showed a power of 78% for predicting coronary calcification. Coronary calcium score correlated with age (p less than 0.01) and triglycerides (p less than 0.05).

CONCLUSIONS

The close relation between coronary calcium and extracoronary plaques suggests that echography of extracoronary vessels could aid in the screening of coronary atherosclerosis in high-risk, asymptomatic individuals.