bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective loss of microvascular endothelial function in human hypercholesterolemia.
Authors: Gilligan D M , Guetta V , Panza J A , García C E , Quyyumi A A , Cannon R O
Published: June 2012

BACKGROUND

Endothelial dysfunction is increasingly recognized as an early and important feature of vascular disease. Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia, although it is unknown whether this defect is selective for some pathways of nitric oxide production or indicates a more generalized abnormality of endothelial function. The aim of this study was to further elucidate the nature of endothelial dysfunction in human hypercholesterolemia by comparing vascular responses of agonists that use different signal transduction pathways to activate production of nitric oxide.

METHODS AND RESULTS

Forearm flow was measured in 12 hypercholesterolemic patients (total cholesterol, 286 +/- 35 mg/dL [mean +/- SD]) aged 50 +/- 11 years and in 12 healthy subjects (total cholesterol, 173 +/- 27 mg/dL) aged 48 +/- 7 years using strain-gauge plethysmography and brachial artery drug infusions. The endothelium-dependent vasodilators used were acetylcholine (7.5, 15, and 30 micrograms/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin (100, 200, and 400 ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside (0.8, 1.6, and 3.2 micrograms/min) was used to test endothelium-independent vasodilation. The maximum flow in response to acetylcholine was markedly impaired in patients compared with healthy subjects (8.0 +/- 5.1 versus 17.5 +/- 7.7 mL.min-1. 100 mL-1, P = .002). However, the maximum forearm flow in response to bradykinin was similar in the two groups (13.0 +/- 4.5 versus 16.2 +/- 5.5 mL.min-1 x 100 mL-, P = .14), as was the maximum flow in response to sodium nitroprusside (7.0 +/- 2.8 versus 8.4 +/- 2.2 mL.min-1 x 100 mL-1, P = .13). NG-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, reduced the maximum forearm vasodilation induced by bradykinin to the same extent in patients and in healthy subjects (-29 +/- 8% versus -32 +/- 6% reduction in peak flow, P = .80), with similar maximum flows in response to bradykinin (9.2 +/- 4.0 versus 10.4 +/- 2.6 mL.min-1 x 100 mL-1, P = .35).

CONCLUSIONS

Hypercholesterolemic patients are capable of normal nitric oxide bioavailability in response to bradykinin. Impairment of microvascular endothelial vasodilator function in human hypercholesterolemia is selective, and the defect occurs at the level of the acetylcholine receptor or its signal transduction pathway.
Utrophin localization in normal and dystrophin-deficient heart.
Authors: Pons F , Robert A , Fabbrizio E , Hugon G , Califano J C , Fehrentz J A , Martinez J , Mornet D
Published: June 2012

BACKGROUND

The localization of dystrophin at the sarcolemma of cardiac skeletal fibers and cardiac Purkinje fibers has been described. Dystrophin deficiency produces clinical manifestations of disease in skeletal muscles and hearts of patients with Duchenne and Becker muscular dystrophy. Utrophin (or dystrophin-related protein), a dystrophin homologous protein, was found to be expressed in fetal muscles and reexpressed in dystrophin-deficient skeletal muscle fibers. We therefore examined utrophin expression in normal and in dystrophin-deficient hearts.

METHODS AND RESULTS

The expression and subcellular distribution of utrophin was examined in cardiac muscle by immunoblot and immunofluorescence analysis in normal bovine heart compared with dystrophin. Utrophin expression was also examined in normal and dystrophin-deficient hearts of MDX mice. Three monoclonal antibodies reacting with dystrophin and utrophin solely or reacting with both proteins along with two polyclonal antibodies reacting with either utrophin or dystrophin and utrophin were tested. In normal bovine heart, utrophin was not expressed at the periphery of fibers but was strongly expressed in intercalated disks and in the cytoplasm of cardiac Purkinje fibers. In cardiocytes, utrophin was colocalized along transverse T tubules with dystrophin. Dystrophin was present at the periphery of cardiocytes and cardiac Purkinje fibers as well as in transverse T tubules but was absent or faintly expressed in intercalated disks. The results with monoclonal and polyclonal antibodies were identical. Western blot analysis revealed that the detected molecules corresponded only to a 400-kD protein band and not to possible shorter transcripts of utrophin or dystrophin (apo-utrophin or apo-dystrophin). In dystrophin-deficient hearts of MDX mice, utrophin alone was abundant but not organized in the same networklike distribution.

CONCLUSIONS

This first localization of utrophin in normal heart (in Purkinje fibers, transverse tubules, and intercalated disks) showed a distinct subcellular localization of this protein with dystrophin, suggesting an important function of this protein in intercellular communication. In dystrophin-deficient hearts of MDX mice, utrophin alone is overexpressed as in skeletal muscle sarcolemma, an area normally occupied by dystrophin but not organized in the same networklike distribution.
Role of microtubules in contractile dysfunction of hypertrophied cardiocytes.
Authors: Tsutsui H , Tagawa H , Kent R L , McCollam P L , Ishihara K , Nagatsu M , Cooper G
Published: June 2012

Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressure-hypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.
Heart disease, cancer, and stroke mortality trends and their interrelations. An international perspective.
Authors: Thom T J , Epstein F H
Published: June 2012

BACKGROUND

Changes in mortality from heart disease, cancer, and stroke over recent decades in many countries have received much attention. However, comprehensive and concurrent analyses of these trends and their effect on total mortality have been lacking. Moreover, the extent to which the trends for one disease may relate to those for another disease is unknown. Concordance of trends for major diseases would suggest that they have common causes and thus may be responsive to the same preventive measures.

METHODS AND RESULTS

Age-adjusted death rates for total mortality and mortality from heart disease, stroke, lung cancer, and cancer other than lung cancer were obtained for the years 1950 to 1987 in 27 countries by sex and ages 35 to 74 years from the World Health Organization statistical reports. Concordance of mortality trends was assessed for ages 35 to 74 between 1950 and 1983 through visual inspection and semiquantitative measurements of percentage change over time. The epidemic increase in heart disease mortality ended in the 1960s or 1970s in most industrialized countries; death rates often declined very steeply. Stroke mortality also changed from an increase to a decline or from a modest to a steep decline in the 1960s or 1970s. Lung cancer mortality slopes generally changed from a steep increase to either a modest increase, a flat trend, or a decline; the changes in slope are lagging behind those for heart disease and stroke. These improvements influenced trends for total mortality. Cancer other than lung cancer trends are less distinct than those for the three other causes of mortality. Yet, testing them for concordance with heart disease trends reveals that they are mostly concordant on a time-lag analysis that assumes that heart disease responds more rapidly to a change in lifestyle or environment than cancer. Trends for heart disease and lung cancer in men also tend to be concordant on time-lag analysis. Heart disease and stroke trends have become more concordant with time.

CONCLUSIONS

Trends for mortality from heart disease, stroke, lung cancer, and, less distinctly, cancer other than lung cancer, tend to be similar in different countries, leading to a corresponding similarity in total mortality trends. An analysis of trends for pairs of diseases within countries indicates a tendency toward concordance of trends, suggesting the existence of common causes amenable to the same preventive measures. This analysis of international mortality trends is intended to stimulate further research along these lines, as a guide to preventive and therapeutic action.
Localized arterial wall drug delivery from a polymer-coated removable metallic stent. Kinetics, distribution, and bioactivity of forskolin.
Authors: Lambert T L , Dev V , Rechavia E , Forrester J S , Litvack F , Eigler N L
Published: June 2012

BACKGROUND

Coronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocompatibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug forskolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent.

METHODS AND RESULTS

Stents were used in rabbit carotid arteries (n = 20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140 +/- 39 pg/microL at 4 hours. The adjacent arterial media contained 60 +/- 39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P < .0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P < .005). In another set of rabbits (n = 14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P < .0001).

CONCLUSIONS

A polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties.
Three-dimensional reconstruction of intracoronary ultrasound images. Rationale, approaches, problems, and directions.
Authors: Roelandt J R , di Mario C , Pandian N G , Wenguang L , Keane D , Slager C J , de Feyter P J , Serruys P W
Published: June 2012

Although intracoronary ultrasonography allows detailed tomographic imaging of the arterial wall, it fails to provide data on the structural architecture and longitudinal extent of arterial disease. This information is essential for decision making during therapeutic interventions. Three-dimensional reconstruction techniques offer visualization of the complex longitudinal architecture of atherosclerotic plaques in composite display. Progress in computer hardware and software technology have shortened the reconstruction process and reduced operator interaction considerably, generating three-dimensional images with delineation of mural anatomy and pathology. The indications for intravascular ultrasonography will grow as the technique offers the unique capability of providing ultrasonic histology of the arterial wall, and the need for a three-dimensional display format for comprehensive analysis is increasingly recognized. Consequently, three-dimensional imaging is being rapidly implemented in the catheterization laboratories for guidance of intracoronary interventions and detailed assessment of their results. However exciting the prospects may be, three-dimensional reconstructions at present remain partially artificial because the true spatial position of the imaging catheter tip is not recorded, and shifts in its location and curves of the arterial lumen result in pseudoreconstructions rather than true reconstructions. In this report, we address the principles of three-dimensional reconstruction with a critical review of its limitations. Potential solutions for refinement of this exciting imaging modality are presented.
Ca(2+)-transporting ATPase, phospholamban, and calsequestrin levels in nonfailing and failing human myocardium.
Authors: Movsesian M A , Karimi M , Green K , Jones L R
Published: June 2012

BACKGROUND

Observations of abnormalities in the diastolic components of intracellular Ca2+ transients in failing human left ventricular myocardium have raised the possibility that reductions in the level or function of sarcoplasmic reticulum proteins involved in Ca2+ transport contribute to the pathophysiology of dilated cardiomyopathy in humans. Functional assays, however, have revealed no differences in ATP-dependent Ca2+ transport or its modulation by phospholamban in sarcoplasmic reticulum-enriched microsomes prepared from nonfailing and failing human left ventricular myocardium. The purpose of the present study was to quantify protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin directly in nonfailing and failing human left ventricular myocardium.

METHOD AND RESULTS

Total protein extracts were prepared from nonfailing left ventricular myocardium from the hearts of unmatched organ donors with normal left ventricular contractility (n = 6) and from failing left ventricular myocardium from the excised hearts of transplant recipients with class IV heart failure resulting from idiopathic dilated cardiomyopathy (n = 6). Ca(2+)-transporting ATPase, phospholamban, and calsequestrin contents were determined by quantitative immunoblotting with monoclonal and affinity-purified polyclonal antibodies. The levels of the three proteins were identical in nonfailing and failing human left ventricular myocardium.

CONCLUSIONS

These results indicate that protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin are not diminished in failing human left ventricular myocardium and that downregulation of the Ca(2+)-transporting ATPase and phospholamban is not part of the molecular pathophysiology of dilated cardiomyopathy in humans.
Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction.
Authors: Cambien F , Costerousse O , Tiret L , Poirier O , Lecerf L , Gonzales M F , Evans A , Arveiler D , Cambou J P , Luc G
Published: June 2012

BACKGROUND

The angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradykinin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segregation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probably by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/deletion polymorphism is present in the 16th intron of the ACE gene (ACE I/D) and appears to be a very good marker for ACE Ss. The biological role of ACE suggests that the ACE gene polymorphism could affect the predisposition to myocardial infarction (MI).

METHODS AND RESULTS

We have recently shown, in a large case-control study (ECTIM), that the marker allele D of the ACE gene, which is associated with higher levels of ACE in plasma and cells, was more frequent in male patients with MI than in control subjects, especially in patients considered at low risk. ACE activity has now been measured from frozen aliquots of plasma in a large subsample of the ECTIM study (n = 1086). Plasma ACE level did not differ between patients and control subjects in the older age group (> or = 55 years) but was higher in patients than in control subjects in the younger age group (< 55 years); P < .005 after adjustment on ACE I/D and other risk factors. In patients, plasma ACE levels decreased with age (R = -.225, P < 10(-4)), but in control subjects no such trend was observed. In the low-risk group (ApoB < 1.25 mg/dL, body mass index < 26 kg/m2, and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozygotes and heterozygotes for the ACE I allele (P < .015). Analysis of the distribution of plasma ACE by using commingling analysis conditional on the marker genotype ACE I/D enabled us to infer the frequencies and effects of the postulated ACE Ss genotypes. The results suggest that the higher plasma ACE levels in patients than in control subjects in the younger age group were due to a difference in frequency of the postulated S allele (.47 versus .36).

CONCLUSIONS

These results extend our previous findings and indicate that plasma ACE level may be a risk factor for MI, independent of the ACE I/D polymorphism.
Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.
Authors: Dekker J M , Schouten E G , Klootwijk P , Pool J , Kromhout D
Published: June 2012

BACKGROUND

Heart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men.

METHODS AND RESULTS

From 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Age-adjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors.

CONCLUSIONS

These results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.
Scopolamine improves autonomic balance in advanced congestive heart failure.
Authors: La Rovere M T , Mortara A , Pantaleo P , Maestri R , Cobelli F , Tavazzi L
Published: June 2012

BACKGROUND

Sympathetic hyperactivity and parasympathetic withdrawal in patients with congestive heart failure correlate closely with disease severity and overall survival. The modulating effects of drugs on the autonomic dysfunction may contribute to improve survival. Low-dose scopolamine has a vagomimetic effect in normal subjects and patients after acute myocardial infarction. We assessed whether transdermal scopolamine would increase vagal activity in patients with congestive heart failure.

METHODS AND RESULTS

Heart rate variability was assessed at baseline, 24 hours after one patch of transdermal scopolamine, and 48 hours after scopolamine withdrawal in 21 patients with moderate to severe heart failure. Scopolamine increased both time- and frequency-domain parameters of heart rate variability. Specifically, the mean RR interval and its SD increased by 5.5% (P < .001) and 45% (P < .001), respectively. The change remained significant when corrected for mean heart rate with a 39% (P < .01) increase of the coefficient of variation. The absolute power of the high-frequency component was also significantly augmented. All the parameters returned to baseline after scopolamine withdrawal. Individual analysis showed that in the 7 patients in whom scopolamine did not increase mean RR interval, heart rate variability did not change.

CONCLUSIONS

Transdermal scopolamine increases vagal activity as assessed by heart rate variability in patients with congestive heart failure. This autonomic modulation does not occur in all patients and can be predicted by RR interval changes. Whether such restoration of the autonomic balance might have beneficial effects in the long-term management of patients with congestive heart failure remains to be determined.
Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies.
Authors: Otto C M , Kuusisto J , Reichenbach D D , Gown A M , O'Brien K D
Published: June 2012

BACKGROUND

Nonrheumatic stenosis of trileaflet aortic valves, often termed senile or calcific valvular aortic stenosis, is considered a "degenerative" process, but little is known about the cellular or molecular factors that mediate its development.

METHODS AND RESULTS

To characterize the developing aortic valvular lesion, we performed histological and immunohistochemical studies on Formalin-fixed and methanol-Carnoy's-fixed paraffin-embedded aortic valve leaflets or on frozen sections obtained at autopsy from 27 adults (age, 46 to 82 years) with normal leaflets (n = 6), mild macroscopic leaflet thickening (n = 15), or clinical aortic stenosis (n = 6). Focal areas of thickening ("early lesions") were characterized by (1) subendothelial thickening on the aortic side of the leaflet, between the basement membrane (PAS-positive) and elastic lamina (Verhoeff-van Gieson), (2) the presence of large amounts of intracellular and extracellular neutral lipids (oil red O) and fine, stippled mineralization (von Kossa), and (3) disruption of the basement membrane overlying the lesion. Regions of the fibrosa adjacent to these lesions were characterized by thickening and by protein, lipid, and calcium accumulation. Control valves showed none of these abnormalities. Immunohistochemical studies were performed using monoclonal antibodies directed against macrophages (anti-CD68 or HAM-56), and contractile proteins of smooth muscle cells or myofibroblasts (anti-alpha-actin and HHF-35) or rabbit polyclonal antiserum against T lymphocytes (anti-CD3). In normal valves, scattered macrophages were present in the fibrosa and ventricularis, and occasional muscle actin-positive cells were detected in the proximal portion of the ventricularis near the leaflet base, but no T lymphocytes were found. In contrast, early lesions were characterized by the presence of an inflammatory infiltrate composed of non-foam cell and foam cell macrophages, occasional T cells, and rare alpha-actin-positive cells. In stenotic aortic valves, a similar but more advanced lesion was seen.

CONCLUSIONS

The early lesion of "degenerative" aortic stenosis is an active inflammatory process with some similarities (lipid deposition, macrophage and T-cell infiltration, and basement membrane disruption) and some dissimilarities (presence of prominent mineralization and small numbers of smooth muscle cells) to atherosclerosis.
Effect of an eccentric severe stenosis on fibrin(ogen) deposition on severely damaged vessel wall in arterial thrombosis. Relative contribution of fibrin(ogen) and platelets.
Authors: Mailhac A , Badimon J J , Fallon J T , Fernández-Ortiz A , Meyer B , Chesebro J H , Fuster V , Badimon L
Published: June 2012

BACKGROUND

Coronary thrombosis is a dynamic process dependent on the pathological substrate, the local shear forces, and blood factors.

METHODS AND RESULTS

We investigated the effect of a severe (80%) eccentric stenosis on fibrin(ogen) interaction with a deeply damaged vessel wall, its relation to platelet deposition in thrombus formation, and the influence of time on thrombus growth. Porcine 125I-fibrinogen and autologous 111In-platelets were injected into pigs instrumented for extracorporeal circulation and treated with low-dose heparin (aPTT ratio < 1.5) that has been previously shown and herein confirmed not to affect platelet and/or fibrin(ogen) attachment. Tunica media, as a model of severely injured vessel wall, was mounted in a tubular perfusion chamber containing an eccentric axisymmetric sinusoidal stenosis obstructing the lumen and exposed for 1, 5, and 10 minutes to perfusing blood. A shear rate of 424 s-1 at the laminar, parallel parabolic local flow perfused segments one to two orders of magnitude greater at the apex of the stenosis. Fibrin(ogen) deposition, its axial distribution with respect to the apex, and its relation to platelet deposition were determined by an ex vivo analysis of the test substrates. Fibrin(ogen) and platelet deposition were both significantly higher at the apex of the stenosis than at either the prestenotic or poststenotic area at all the studied perfusion times (P < .02). However, fibrin(ogen) deposition demonstrated a significantly smaller degree of increase from the prestenotic area to the apex as well as a smaller degree of decrease from the latter to the poststenotic region, compared with platelet deposition (P < .05). Although both fibrin(ogen) and platelet deposition increased over time, the ratio of fibrin(ogen) to platelets showed a progressive decrease that became significant from 5 to 10 minutes (P < .03) at either low or high shear rate. The rate of platelet deposition was relatively constant; however, fibrin(ogen) deposition progressively decreased, especially at the apex.

CONCLUSIONS

On severely damaged vessel wall, fibrin(ogen) and platelet deposition is maximal at the apex of the stenosis where shear rate is extremely high and parallel streamlines are deformed. Nevertheless, fibrin(ogen) deposition is significantly less dependent on high shear rate than is platelet deposition, and the pattern is not influenced by time. Finally, fibrin(ogen) deposition appears to be predominant in the thrombus layers adjacent to a severely damaged vessel wall regardless of the local shear stress levels and flow conditions.
Electrocardiographic characteristics and catheter ablation of parahissian accessory pathways.
Authors: Haissaguerre M , Marcus F , Poquet F , Gencel L , Le Métayer P , Clémenty J
Published: June 2012

BACKGROUND

Accessory pathways may be located in close proximity to the His bundle, resulting in a high risk of heart block during attempted surgical or electrical interruption of these pathways. This study reports the prevalence, ECG characteristics, and results of catheter ablation of parahissian accessory pathways. They were defined on the basis of both the presence of a high amplitude (> 0.1 mV) of His bundle potential at the ablation site and an exclusion of anteroseptal or midseptal location of the accessory pathway.

METHODS AND RESULTS

Eight patients with a parahissian accessory pathway were identified among 582 consecutive patients who underwent radiofrequency ablation of an accessory pathway. They were six males and two females with a mean age of 21 +/- 9 years. During maximal preexcitation, the ECG showed a positive delta wave in leads I, II, and a VF in all patients: six had a negative delta wave in leads V1 and V2 instead of the positivity usually observed in anteroseptal accessory pathways. This pattern had a sensitivity of 75%, a specificity of 96%, a positive predictive value of 86%, and a negative predictive value of 93% for a parahissian location in comparison with a group of 28 patients with anteroseptal accessory pathways. At the successful ablation site, the mean amplitude of the His bundle potential was 0.2 +/- 0.1 (0.12 to 0.4 mV). All accessory pathways were successfully ablated without causing heart block using 5 to 20 W of radiofrequency energy.

CONCLUSIONS

Parahissian accessory pathways have a preexcitation pattern that is distinctive from that of anteroseptal accessory pathways. Catheter ablation of these pathways is feasible using low energy with preservation of normal atrioventricular conduction.
Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty.
Authors: Foley D P , Melkert R , Serruys P W
Published: June 2012

BACKGROUND

Although coronary angioplasty is increasingly applied in the treatment of multivessel disease and a broadening range of vessel size, the influence of vessel size itself on the late results of intervention is unresolved. An influence of vessel size on late outcome would carry implications for the application and evaluation of interventional devices, which are selectively used in larger or smaller vessels. The purpose of the present study was to investigate the influence of vessel size on both the restenosis process and late angiographic outcome in a large homogeneous patient group after successful percutaneous transluminal coronary angioplasty (PTCA).

METHODS AND RESULTS

The study population comprised 3072 patients with 3736 successfully dilated native primary coronary artery lesions and satisfactory quantitative angiographic analysis in multiple identical projections before and after PTCA and at a 6-month follow-up. Late luminal loss, minimal luminal diameter (MLD) at follow-up, and net luminal gain, as well as percent diameter stenosis at follow-up, net gain in percent diameter stenosis, restenosis rates (according to three definitions), and net gain index, were all compared among nine equally sized groups (noniles) according to vessel size. A direct influence of vessel size on continuous measures of late result was also evaluated by linear regression. These evaluations provided conflicting information with no consistent influence of vessel size emerging. To elucidate the independent influence of vessel size on the restenosis process (late loss) and late angiographic outcome (MLD at follow-up), multiple linear regression analysis was performed taking into account luminal gain, preprocedural MLD, and lesion location. In this manner, vessel size was found to be exert a significantly positive influence on MLD at follow-up (P < .0001) and an equally negative effect on loss. Correcting for vessel size by using percent stenosis measurements led to an anticipated neutralization of this influence. Lesion location in the left anterior descending coronary artery was found to be independently associated with greater loss and smaller MLD at follow-up (P < .0001).

CONCLUSIONS

Increasing coronary vessel size was found to be independently predictive of decreasing late luminal loss and increasing follow-up MLD after successful balloon angioplasty. Apparently superior or inferior late angiographic results of new interventional devices may thus be explained in part by preferential use in larger or smaller vessels, respectively. Devices that can safely optimize the short-term result of intervention may realize their ultimate long-term value in larger coronary vessels.
Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Atakr Multicenter Investigators Group.
Authors: Calkins H , Prystowsky E , Carlson M , Klein L S , Saul J P , Gillette P
Published: June 2012

BACKGROUND

The purpose of this study was to evaluate electrode temperatures obtained using a radiofrequency ablation system that incorporates closed loop feedback control to achieve preset target electrode temperatures and to determine if closed loop temperature control results in a lower incidence of developing a coagulum.

METHODS AND RESULTS

Two hundred seventy patients underwent catheter ablation of atrioventricular nodal reentrant tachycardia, an accessory pathway, and/or the atrioventricular junction using an ablation system incorporating closed loop feedback control. Forty-five patients underwent catheter ablation in the power control mode in which power output was fixed, and 225 patients underwent catheter ablation in the temperature control mode. A coagulum occurred during 0.8% of radiofrequency applications in the temperature control mode versus 2.2% in the power control mode (P < .01). Electrode temperatures were within 10 degrees C of the targeted temperature during 35% of applications in the temperature control mode. Ability to achieve the targeted electrode temperature was related to the target, with radiofrequency energy applications at the atrioventricular junction resulting in the highest temperatures (70 +/- 12 degrees C) and those for ablation of the atrioventricular node the lowest (59 +/- 11 degrees C, P < .001), using a maximum of 50 W of power for both. Electrode temperatures were higher during ablation of left free wall and posteroseptal pathways than during ablation of right free wall and septal pathways. The mean and minimum temperatures associated with success were 64 +/- 12 degrees C and 44 degrees C, respectively. Overall, the electrode temperatures at successful and unsuccessful ablation sites did not differ (P > .05).

CONCLUSIONS

Temperature monitoring with closed loop control of power output facilitates radiofrequency catheter ablation procedures by minimizing the probability of developing a coagulum while ensuring maximum lesion formation.
Rapid two-stage arterial switch operation. Acquisition of left ventricular mass after pulmonary artery banding in infants with transposition of the great arteries.
Authors: Boutin C , Jonas R A , Sanders S P , Wernovsky G , Mone S M , Colan S D
Published: June 2012

BACKGROUND

Banding of the pulmonary artery (PAB) in preparation for arterial switch operation (ASO) in patients with transposition of the great arteries (TGA) represents a unique model of acute left ventricular pressure overload in humans.

METHODS AND RESULTS

To establish the rate, magnitude, and determinants of left ventricular hypertrophy and the acute effect on ventricular function, serial bidimensional echocardiographic evaluations were performed on 26 patients with TGA after PAB. Mass, volume, and ejection fraction of the left ventricle were measured. Cardiac catheterization data before PAB and again before ASO were reviewed. The mean interval between the PAB and ASO was 9 +/- 4 days. The left ventricular to right ventricular pressure ratio before PAB was 0.5 and increased to 1.0 before ASO. The mean percentage increase in left ventricular mass from PAB to ASO was 96%, 95% of which was achieved in the first 7 days. The average rate of left ventricular hypertrophy for the entire period was 0.06 g/h and was 0.19 g/h during the interval from PAB to attainment of maximum left ventricular mass. The most rapid rate of hypertrophy was seen by day 2, with an exponential fall in the growth rate thereafter approaching zero by day 7. Ejection fraction was significantly reduced at 12 hours after PAB, but mean values returned to pre-PAB levels by 3.5 days after banding. The absolute rate of left ventricular hypertrophy correlated directly with body surface area but not to other hemodynamic variables.

CONCLUSIONS

Doubling of left ventricular mass can be achieved in 1 week after PAB. Function falls acutely due to afterload excess and/or depressed contractility but recovers rapidly as compensatory hypertrophy occurs.
Infantile dilated cardiomyopathy. Relation of outcome to left ventricular mechanics, hemodynamics, and histology at the time of presentation.
Authors: Matitiau A , Perez-Atayde A , Sanders S P , Sluysmans T , Parness I A , Spevak P J , Colan S D
Published: June 2012

BACKGROUND

For patients with acute dilated cardiomyopathy, definition of prognosis and of clinical features predictive of outcome is particularly important due to the availability of cardiac transplantation and other innovative treatment strategies.

METHODS AND RESULTS

We reviewed our experience with 24 children under 2 years of age with dilated congestive cardiomyopathy to determine outcome and potential predictive variables. Clinical, serological, ECG, echocardiographic, hemodynamic, and histological findings were analyzed. Idiopathic cardiomyopathy or myocarditis constituted 29% of the patients presenting with congestive heart failure without structural heart disease. Among these patients, 45% recovered completely, 25% survived with persistent left ventricular dysfunction, and 30% died. All except one of the deaths occurred during the first 2 months after presentation. Poorer outcome and higher mortality were associated with a more severely depressed left ventricular ejection fraction and/or a more spherical left ventricular shape at presentation. Histological evidence of myocardial inflammation was a favorable prognostic indicator, whereas histological evidence of endocardial fibroelastosis was associated with a poor outcome. During the recovery phase, diastolic volume fell rapidly. Ventricular mass was elevated from the earliest observations and fell more slowly, with persistent elevation of the mass-to-volume ratio up to 2 years. Function and contractility improved over the first several months in most patients who recovered, although in occasional patients continued improvement was seen for as long as 2 years after presentation.

CONCLUSIONS

Histological and echocardiographic features can be used to identify patients at particularly high risk for death. To have any impact on outcome, decisions about cardiac transplantation must be reached rapidly, since almost all deaths occurred within the first 2 months after presentation. Recovery of function is often rapid, but continued improvement may be seen for as long as 2 years.
Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury.
Authors: Hamon M , Vallet B , Bauters C , Wernert N , McFadden E P , Lablanche J M , Dupuis B , Bertrand M E
Published: June 2012

BACKGROUND

Nitric oxide (NO), in addition to its potent vasorelaxant properties, may participate in growth regulation of cultured smooth muscle cells. It was recently demonstrated that in vivo endothelial injury induces the production of NO from L-arginine in the arterial wall.

METHODS AND RESULTS

We studied the effects of long-term administration of L-arginine, the precursor of NO, on neointimal thickening and on neoendothelium-dependent vasorelaxation 4 weeks after balloon denudation of normocholesterolemic rabbit iliac arteries. Rabbits were fed with either a standard diet or a diet supplemented with L-arginine (2.25%) in their drinking water 3 days before and during 4 weeks after balloon denudation. The effectiveness of L-arginine supplementation was confirmed by measurement of plasma arginine levels. L-Arginine had no effect on hemodynamic parameters. All animals were killed 4 weeks after balloon denudation, and a digital histomorphometric analysis of three serial nonconsecutive histological cross sections per iliac artery was performed. Intimal thickening was reduced (P < .05) from 0.43 +/- 0.08 (SE) mm2 in controls (n = 8) to 0.24 +/- 0.02 mm2 in treated animals (n = 8). Ten animals (n = 5 in each group) were used for in vitro vasoreactivity assessment 4 weeks after balloon denudation. Neoendothelium-dependent acetylcholine-induced relaxation (10(-8) mol/L to 3.10(-5) mol/L) in treated animals (Emax = -24.1 +/- 5.5%) was significantly greater than in controls (Emax = -8.9 +/- 2.2%). Endothelium-independent relaxation did not differ between groups (Emax = -58.1 +/- 6.5% in L-arginine-supplemented animals versus -52.9 +/- 6.8% in controls).

CONCLUSIONS

Our results demonstrate that L-arginine, a precursor of NO, reduces neointimal thickening after balloon denudation and improves neoendothelial-dependent acetylcholine-induced relaxation.
Spontaneous delayed recovery of perfusion and contraction after the first 5 weeks after anterior infarction. Evidence for the presence of hibernating myocardium in the infarcted area.
Authors: Galli M , Marcassa C , Bolli R , Giannuzzi P , Temporelli P L , Imparato A , Silva Orrego P L , Giubbini R , Giordano A , Tavazzi L
Published: June 2012

BACKGROUND

In patients with ventricular dysfunction caused by stunning or hibernation, it is not clear when complete recovery of the salvaged myocardium occurs after acute myocardial infarction. The purpose of this study was to determine whether a delayed recovery of perfusion and contraction continues even after the subacute phase.

METHODS AND RESULTS

We prospectively studied 71 consecutive male patients with first uncomplicated Q-wave anterior infarction. Resting regional blood flow distribution and contraction were assessed quantitatively 5 weeks and 7 months after the acute phase by serial sestamibi tomography and two-dimensional echocardiography. Coronary angiography also was performed in 52 patients. Overall, at 7 months there was an improvement in the perfusion defect severity (1019 +/- 811 versus 1365 +/- 821 at 5 weeks, P < .001) as well as in the extent of abnormal wall motion (28 +/- 19% versus 32 +/- 15%, P < .001) and left ventricular ejection fraction (53 +/- 14% versus 50 +/- 13%, P < .01). Among the 68 of 71 patients showing resting perfusion defects at 5 weeks, two groups were identified: 47 (group 1) who showed a significant (beyond the reproducibility limits) 7-month reduction of the resting perfusion defect, and 21 patients (group 2) in whom the perfusion defect remained unchanged. Ejection fraction and the extent of abnormal wall motion significantly (P < .01) improved in group 1 but not in group 2. Despite the presence of a comparable perfusion defect size between the two groups at 5 weeks after infarction, group 1 already showed a better regional and global ventricular function (P < .05). No significant differences were found between the two groups regarding age, medical therapy, the extent of underlying coronary disease, thrombolysis in the acute phase, Thrombolysis in Myocardial Infarction grade of the infarct-related vessel, and presence of collaterals on angiography.

CONCLUSIONS

After anterior Q-wave infarction, the recovery of perfusion and wall motion may continue well after the subacute phase. Several patients exhibit relative hypoperfusion in viable tissue as late as 5 weeks after infarction, and a significant improvement of perfusion in the infarcted area commonly is observed between 5 weeks and 7 months. This delayed improvement of perfusion is associated with a delayed improvement of contractile function in the infarcted area after the first 5 weeks, which may continue for up to 7 months, suggesting the presence of hibernating myocardium in the infarcted area. Despite similar perfusion defect sizes, the level of regional function can be different at 5 weeks, and measurements taken around this time may not accurately estimate the eventual recovery of function.
Direct thrombin inhibitors in cardiovascular medicine.
Authors: Lefkovits J , Topol E J
Published: June 2012

Currently used antithrombotics such as heparin have a number of potential limitations that may be overcome by the new class of agents that directly inhibit thrombin. These agents variously block the active catalytic and/or the anion binding exosites of the thrombin molecule and are potent and specific inhibitors of thrombin's many biological actions, as demonstrated by in vitro and animal models of thrombosis. Preliminary data indicate that the direct antithrombins are safe and efficacious in humans, and their use in acute coronary syndromes and coronary angioplasty in place of heparin has yielded promising early results. Phase III trials in these clinical settings are currently under way. Newer antithrombotics that inhibit thrombin generation and thrombin activity at various strategic points within the coagulation cascade are also in the early stages of development.
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.