Head-to-head comparison of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia in an animal model of coronary artery stenosis

To compare the sensitivity of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia we produced a physiologically significant stenosis in the left circumflex artery of 14 open-chest dogs (range: 50 to 89% reduction in luminal diameter). In each study, dobutamine (5 to 40 µg kg-1 min-1 in 3-min stages) and pacing (20 bpm increments, each 2 min, up to 260 bpm) were performed randomly, and then followed by dipyridamole (up to 0.84 mg/kg over 10 min). The positivity of stress echocardiography tests was quantitatively determined by a significant (P<0.05) reduction of or failure to increase absolute and percent systolic wall thickening in the stenotic artery supplied wall, as compared to the opposite wall (areas related to the left anterior descending artery). Systolic and diastolic frozen images were analyzed off-line by two blinded observers in the control and stress conditions. The results showed that 1) the sensitivity of dobutamine, dipyridamole and pacing stress tests was 57, 57 and 36%, respectively; 2) in animals with positive tests, the mean percent change of wall thickening in left ventricular ischemic segments was larger in the pacing (-19 ± 11%) and dipyridamole (-18 ± 16%) tests as compared to dobutamine (-9 ± 6%) (P = 0.05), but a similar mean reduction of wall thickening was observed when this variable was normalized to a control left ventricular segment (area related to the left anterior descending artery) (pacing: -16 ± 7%; dipyridamole: -25 ± 16%; dobutamine: -26 ± 10%; not significant), and 3) a significant correlation was observed between magnitude of coronary stenosis and left ventricular segmental dysfunction induced by ischemia in dogs submitted to positive stress tests. We conclude that the dobutamine and dipyridamole stress tests showed identical sensitivities for the detection of myocardial ischemia in this one-vessel disease animal model with a wide range of left circumflex artery stenosis. The pacing stress test was less sensitive, but the difference was not statistically significant. The magnitude of segmental left ventricular dysfunction induced by ischemia was similar in all stress tests evaluated.

Successful scale-up of human embryonic stem cell production in a stirred microcarrier culture system

Future clinical applications of human embryonic stem (hES) cells will require high-yield culture protocols. Currently, hES cells are mainly cultured in static tissue plates, which offer a limited surface and require repeated sub-culturing. Here we describe a stirred system with commercial dextran-based microcarriers coated with denatured collagen to scale-up hES cell production. Maintenance of pluripotency in the microcarrier-based stirred system was shown by immunocytochemical and flow cytometry analyses for pluripotency-associated markers. The formation of cavitated embryoid bodies expressing markers of endoderm, ectoderm and mesoderm was further evidence of maintenance of differentiation capability. Cell yield per volume of medium spent was more than 2-fold higher than in static plates, resulting in a significant decrease in cultivation costs. A total of 10(8) karyotypically stable hES cells were obtained from a unitary small vessel that needed virtually no manipulation during cell proliferation, decreasing risks of contamination. Spinner flasks are available up to working volumes in the range of several liters. If desired, samples from the homogenous suspension can be withdrawn to allow process validation needed in the last expansion steps prior to transplantation. Especially when thinking about clinical trials involving from dozens to hundreds of patients, the use of a small number of larger spinners instead of hundreds of plates or flasks will be beneficial. To our knowledge, this is the first description of successful scale-up of feeder- and Matrigel™-free production of undifferentiated hES cells under continuous agitation, which makes this system a promising alternative for both therapy and research needs.

The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma

La sclérodermie (sclérose systémique, ScS) est une maladie auto-immune du tissu conjonctif caractérisée  par  l’épaississement  de  la  peau,  l’apparition  spontanée de lésions cicatricielles, des maladies   des   vaisseaux   sanguins,   divers   degrés   d’inflammation,   en   association   avec   un   système   immunitaire hyperactif. La pathogénèse exacte de cette maladie est inconnue et aucun traitement approprié   n’est   disponible.   La fibrose est un élément distinctif de la maladie de ScS et est considérée   résulter   d’une   incapacité   à   mettre   fin   de   façon   appropriée   à   la   réponse   normale   de   réparation   des   plaies.   L’analyse   histologique   du   stade   initial   de   la   ScS   révèle   une   infiltration   périvasculaire de cellules mononucléaires dans le derme, associée à une synthèse accrue de collagène dans les fibroblastes environnants. Ainsi, la compréhension des moyens de contrôler le stade inflammatoire de la ScS pourrait être bénéfique pour contrôler la progression de la maladie peu après son apparition. La mPGES-1 est une enzyme inductible qui agit en aval de la cyclo- oxygénase (COX) pour catalyser spécifiquement la conversion de la prostaglandine (PG) H2 en PGE2. La mPGES-1  joue  un  rôle  clé  dans  l’inflammation,  la  douleur  et  l’arthrite;;  toutefois,  le   rôle de la mPGES-1 dans les mécanismes de fibrose, spécifiquement en rapport avec la ScS humaine, est inconnu. Mon laboratoire a précédemment montré que les souris à mPGES-1 nulle sont résistantes à la fibrose   cutanée   induite   par   la   bléomycine,   à   l’inflammation,   à   l’épaississement  cutané,  à  la  production  de  collagène  et  à  la  formation  de  myofibroblastes.  Sur  la   base  de  ces  résultats,  j’ai  formulé  l’hypothèse  que  l’inhibition pharmacologique de la mPGES-1 régulera à la baisse la production de médiateurs pro-inflammatoires et pro-fibreux au cours de la maladie   de   ScS.   Afin   d’explorer   le   rôle   de   la   mPGES-1   dans   l’inflammation   et   la   fibrose   associées  à  la  maladie  de  ScS,  j’ai  d’abord  examiné  l’expression  de  la  mPGES-1 dans la peau normale comparativement à des biopsies de peau extraites de patients atteints de ScS. Mes résultats ont montré que la mPGES-1 est nettement élevée dans la peau de patients atteints de ScS en comparaison avec la peau humaine normale. De plus, les niveaux de PGE2 dérivés de la mPGES-1 étaient également significativement plus élevés dans les fibroblastes cutanés isolés de patients  atteints  de  ScS  comparativement  aux  fibroblastes  isolés  de  témoins  sains.  J’ai  également   étudié  l’effet  de  l’inhibition pharmacologique de la mPGES-1  sur  l’expression  de  marqueurs  pro- fibreux.   Mes   études   ont   montré   que   l’expression   de   médiateurs   pro-fibreux clés (α-SMA, endothéline-1, collagène de type 1 et facteur de croissance du tissu conjonctif (FCTC)) est élevée dans les fibroblastes cutanés ScS en comparaison avec les fibroblastes cutanés normaux. Un traitement avec un inhibiteur de la mPGES-1 a eu pour effet de réduire significativement l’expression  de  l’α-SMA,  de  l’endothéline-1, du collagène de type 1 mais pas du FCTC dans les fibroblastes  ScS,  sans  effet  significatif  sur  les  fibroblastes  normaux.  J’ai  en  outre  examiné  l’effet   de  l’inhibition  de  la  mPGES-1 sur des cytokines pro-inflammatoires clés impliquées dans la pathologie de la ScS, incluant IL-6, IL-8 et MCP-1.  L’inhibition  pharmacologique  de  la  mPGES- 1 a eu pour effet de réduire significativement les niveaux de production de cytokines pro- inflammatoires IL6, IL8 et MCP-1 dans les fibroblastes avec lésion ScS comparativement à des fibroblastes non traités. De plus, les patients atteints de ScS ont présenté des niveaux plus élevés de p-AKT, de p-FAK et de p-SMAD3 en comparaison avec les fibroblastes cutanés normaux. L’inhibiteur  de  la  mPGES-1 a pu réguler à la baisse cette expression accrue de p-AKT et de p- FAK, mais pas de p-SMAD3,  dans  les  fibroblastes  ScS.  Ces  résultats  ont  suggéré  que  l’inhibition   de la mPGES-1 pourrait être une méthode viable pour réduire le développement de sclérose cutanée et constituent une cible thérapeutique potentielle pour contrôler les mécanismes fibreux et inflammatoires associés à la pathophysiologie de la maladie de ScS. L’un   des   autres   processus   critiques   reliés   à   l’évolution de la réponse fibreuse associée à la maladie de ScS est la différenciation des fibroblastes en des cellules activées spécialisées iii iv appelées myofibroblastes, responsables de déclencher une signalisation adhésive excessive et le dépôt excessif de matrice extracellulaire,   conduisant   à   la   destruction   de   l’architecture   de   l’organe.   Ainsi,   l’identification   des   facteurs   endogènes   qui   initient/   favorisent   la   différenciation   fibroblaste-myofibroblaste peut mener à des stratégies thérapeutiques prometteuses pour contrôler  l’excès  de  signalisation  adhésive  et  de  fibrose  associé  à  la  maladie  de  ScS.  Des  études   antérieures  dans  le  domaine  de  la  biologie  du  cancer  ont  suggéré  que  l’éphrine  B2,  une  protéine   transmembranaire appartenant à la famille des éphrines, est impliquée dans la signalisation adhésive   et   le   remodelage   extracellulaire.   Cependant,   son   rôle   dans   la   fibrose   n’a   jamais   été   exploré.   Dans   la   deuxième   partie   de   mon   étude,   j’ai   donc   étudié   le   rôle   de   l’éphrine   B2   dans   la   fibrose.   Mes   études   montrent   que   l’expression   de   l’éphrine   B2   est   significativement   augmentée   dans la peau humaine ScS comparativement à la peau normale. Plus important encore, le traitement in vitro de   fibroblastes   de   la   peau   humaine   normale   avec   de   l’éphrine   B2   recombinante est capable de transformer des fibroblastes en cellules myofibroblastiques manifestant toutes les caractéristiques myofibroblastiques typiques, incluant la formation accrue de  fibres  de  tension,  des  adhérences  focales,  l’activation  accrue  de  la  FAK,  un  accroissement  de   l’expression  et  de  la  migration  de  fibroblastes  et  de  leur  adhérence  à  la  fibronectine  à  la  fois  chez   les   fibroblastes   cutanés   normaux   et   ScS.   En   outre,   j’ai   traité   des   souris   avec   de   l’éphrine   B2   recombinante et montré que ces souris ont développé une fibrose cutanée significative associée à une épaisseur dermique et à une synthèse de collagène augmentées, une teneur en hydroxyproline (teneur en collagène) accrue et un nombre accru de myofibroblastes exprimant de   l’α-SMA, une activation augmentée de la FAK et de marqueurs pro-fibreux incluant le collagène de type 1 et le FCTC. Dans  l’ensemble,  mes  études  ont  identifié  deux  médiateurs  endogènes  cruciaux  impliqués  dans  la   propagation  de  l’inflammation  et  de  la  fibrose  associées  à  la  maladie  de  ScS.  L’inhibition  de  la   mPGES-1   pourrait   représenter   une   bonne   stratégie   alternative   pour   contrer   l’inflammation   et   la   fibrose au moins durant les stades précoces de la maladie de ScS. De plus, une signalisation excessive   de   l’éphrine B2 favorise la signalisation adhésive et fibreuse en déclenchant la différenciation   de   fibroblastes   en   myofibroblastes   par   l’activation   de   la   voie   de   signalisation   de   la  FAK.  Ainsi,  l’inhibition  d’éphrine  B2  bloquera  la  formation  de  fibroblastes-myofibroblastes et régulera à la baisse la fibrose associée à la maladie de ScS. En somme, la mPGES-1  et  l’éphrine   B2 semblent toutes deux des cibles attrayantes pour le traitement de la ScS et des troubles fibreux qui y sont reliés.

The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion

SCOPE: Evidence for the benefits of green tea catechins on vascular function is inconsistent, with genotype potentially contributing to the heterogeneity in response. Here, the impact of the catechol-O-methyltransferase (COMT) genotype on vascular function and blood pressure (BP) after green tea extract ingestion are reported. METHODS AND RESULTS: Fifty subjects (n = 25 of the proposed low-activity [AA] and of the high-activity [GG] COMT rs4680 genotype), completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, digital volume pulse (DVP), and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo. A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion. A genotype × treatment interaction was observed for DVP reflection index (p = 0.014), with green tea extract in the AA COMT group attenuating the increase observed with placebo. A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo (p = 0.07). A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group demonstrating a greater concentration (p = 0.049). CONCLUSION: Differences in small vessel tone according to COMT genotype were evident after acute green tea extract.

Produção do tomateiro (Lycopersicon esculentum L.) cultivado em diferentes recipientes e níveis de cálcio na solução nutritiva

Pós-graduação em Agronomia - FEIS

Strategies for Multivessel Revascularization in Patients with Diabetes

BACKGROUND In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease. METHODS In this randomized trial, we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure, and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients' mean age was 63.1 +/- 9.1 years, 29% were women, and 83% had three-vessel disease. The primary outcome occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03). CONCLUSIONS For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.)

Eosinophilic vasculitis: an inhabitual and resistant manifestation of a vasculitis

A 55-year-old woman was referred because of diffuse pruritic erythematous lesions and an ischemic process of the third finger of her right hand. She was known to have anaemia secondary to hypermenorrhea. She presented six months before admission with a cutaneous infiltration on the left cubital cavity after a paravenous leakage of intravenous iron substitution. She then reported a progressive pruritic erythematous swelling of her left arm and lower extremities and trunk. Skin biopsy of a lesion on the right leg revealed a fibrillar, small-vessel vasculitis containing many eosinophils.Two months later she reported Raynaud symptoms in both hands, with a persistent violaceous coloration of the skin and cold sensation of her third digit of the right hand. A round 1.5 cm well-delimited swelling on the medial site of the left elbow was noted. The third digit of her right hand was cold and of violet colour. Eosinophilia (19 % of total leucocytes) was present. Doppler-duplex arterial examination of the upper extremities showed an occlusion of the cubital artery down to the palmar arcade on the right arm. Selective angiography of the right subclavian and brachial arteries showed diffuse alteration of the blood flow in the cubital artery and hand, with fine collateral circulation in the carpal region. Neither secondary causes of hypereosinophilia nor a myeloproliferative process was found. Considering the skin biopsy results and having excluded other causes of eosinophilia, we assumed the diagnosis of an eosinophilic vasculitis. Treatment with tacrolimus and high dose steroids was started, the latter tapered within 12 months and then stopped, but a dramatic flare-up of the vasculitis with Raynaud phenomenon occurred. A new immunosuppressive approach with steroids and methotrexate was then introduced. This case of aggressive eosinophilic vasculitis is difficult to classify into the usual forms of vasculitis and constitutes a therapeutic challenge given the resistance to current immunosuppressive regimens.

[Which clinical symptoms suggest distinct autoantibody measurements?]

The detection of autoantibodies is an important cornerstone in the diagnosis of systemic autoimmune disorders such as autoimmune connectivitides and small vessel vasculitides. Antinuclear antibodies (ANAs ) and antineutrophil cytoplasmic antibodies (c+p-ANCAs) are appropriate diagnostic screening tools for autoimmune connectivitides and small vessel vasculitides. For economic and intellectual/didactic reasons more extensive autoantibody diagnostics should be performed only in particular situations when patients history and clinical exam lead to strong diagnostic suspicion.

Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (213Bi-DOTA-PESIN and 213Bi-AMBA versus 177Lu-DOTA-PESIN)

Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of α-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of α-particles as compared with β-particles. (213)Bi is considered an α-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide α-therapy; however, there is limited knowledge available within this context of use. In this study, two novel (213)Bi-labeled peptides, DOTA-PEG(4)-bombesin (DOTA-PESIN) and DO3A-CH(2)CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH(2) (AMBA), were compared with (177)Lu (β-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with (177)Lu-DOTA-PESIN, (213)Bi-DOTA-PESIN, or (213)Bi-AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive (175)Lu-DOTA-PESIN. The MTD of (213)Bi-DOTA-PESIN and (213)Bi-AMBA was 25 MBq (0.68 mCi) whereas (177)Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, (213)Bi-DOTA-PESIN and (213)Bi-AMBA were significantly more effective than (177)Lu-DOTA-PESIN. At the same time, (177)Lu-DOTA-PESIN showed minimal, (213)Bi-DOTA-PESIN slight, and (213)Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that α-therapy with (213)Bi-DOTA-PESIN or (213)Bi-AMBA is more efficacious than β-therapy. Furthermore, (213)Bi-DOTA-PESIN has a better safety profile than (213)Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide α-therapy treating recurrent prostate cancer.

Tidal volume single breath washout of two tracer gases--a practical and promising lung function test

Background Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF6) and helium (He) using an ultrasonic flowmeter (USFM). Methods The tracer gas mixture contained 5% SF6 and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart. Results USFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF6 and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%. Conclusion The USFM accurately measured relative changes in SF6 and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF6 and He washout patterns during tidal breathing.

Reasons to withhold intra-arterial thrombolysis in clinical practice

BACKGROUND: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6 hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce. METHODS: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center. RESULTS: 76 patients (33.0%) presented within 3 hours, 69 (30%) between 3 and 6 hours of symptom onset and 85 (37%) later than 6 hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6 hours did not undergo arteriography and thrombolysis, mostly because of mild (n = 44) or rapidly improving neurological deficits (n = 13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n = 7), limiting comorbidty (n = 7) and baseline international normalized ratio > 1.7 (n = 1). CONCLUSIONS: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6 hours time window and mild or rapidly improving symptoms.

Clinical relevance of coronary angiography at the time of percutaneous closure of a patent foramen ovale

BACKGROUND: The value of incidental coronary angiography during percutaneous shunt closure to screen for asymptomatic coronary artery disease (CAD) is unknown. METHODS: On the occasion of percutaneous closure of patent foramen ovale (PFO), incidental coronary angiography routinely offered to men >40 and women >50 years, or younger patients with particular risk patterns, was performed in 575 patients (64% men, mean age 55 +/- 10 years, mean 1.5 +/- 1.1 cardiovascular risk factors) without overt history, signs, or symptoms of CAD. RESULTS: CAD was found in 164 patients (29%); 53 (9%) had >or=50% diameter stenoses. Thirty patients (5%) had one-vessel, 13 (2%) two-vessel, and 10 (2%) three-vessel disease. Patients with CAD (n = 164) were older (60 +/- 9 vs. 53 +/- 10 years; P < 0.0001), more frequently male (76% vs. 59%; P = 0.0002), and had a higher body mass index (26.5 +/- 4.0 vs. 25.4 +/- 4.6; P = 0.006) and more cardiovascular risk factors (2.0 +/- 1.1 vs. 1.2 +/- 1.0; P < 0.0001). There were six procedural complications (1%). Two were unequivocally related to coronary angiography: one minor stroke (diplopia), and one iatrogenic dissection of the right coronary ostium requiring stenting. Furthermore, four arteriovenous fistulae at the puncture site requiring elective surgical closure were possibly related to coronary angiography. Forty-five patients (8% of total) underwent percutaneous (n = 43) or surgical (n = 2) revascularization. CONCLUSIONS: In selected asymptomatic patients referred for percutaneous PFO closure, incidental coronary angiography discloses a rather high prevalence of clinically unsuspected CAD. These findings are relevant not only for timely revascularization but also for maintenance of long-term antiplatelet therapy beyond the few months recommended after PFO closure.

Age-dependent differences in demographics, risk factors, co-morbidity, etiology, management, and clinical outcome of acute ischemic stroke

BACKGROUND : Comparisons between younger and older stroke patients including comorbidities are limited. METHODS : Prospective data of consecutive patients with first ever acute ischemic stroke were compared between younger ( 45 years). RESULTS : Among 1004 patients, 137 (14 %) were disease (14 % versus 40 %; p < 0.0001), and a lower mean Charlson co-morbidity index (CCI), (0.18 versus 0.84; p < 0.0001). Tobacco use was more prevalent in the young (39 % versus 26 %; P < 0.0001). Large artery disease (2 % versus 21 %; p < 0.0001), small artery disease (3 % versus 12 %; p = 0.0019) and atrial fibrillation (1 % versus 17 %; p = 0.001) were less common in young patients, while other etiologies (31 % versus 9 %; p < 0.0001), patent foramen ovale or atrial septal defect (44 % versus 26 %; p < 0.0001), and cervical artery dissection (26 % versus 7 %; p < 0.0001) were more frequent. A favorable outcome (mRS 0 or 1) was more common (57.4 % versus 46.9 %; p = 0.023), and mortality (5.1 % versus 12 %; p = 0.009) was lower in the young. After regression analysis, there was no independent association between age and outcome (p = 0.206) or mortality (p = 0.073). Baseline NIHSS score (p < 0.0001), diabetes (p = 0.041), and CCI (p = 0.002) independently predicted an unfavorable outcome. CONCLUSIONS : Younger patients were more likely to be female, had different risk factors and etiologies and fewer co-morbidities. There was no independent association between age and clinical outcome or mortality.

Unprotected left main stenting in the real world: two-year outcomes of the French left main taxus registry

BACKGROUND: Cardiac surgery is the reference treatment for patients with left main (LM) disease, although percutaneous coronary intervention with drug-eluting stents is emerging as a possible alternative. The objective of this registry was to evaluate the 2-year outcome of elective percutaneous coronary intervention for unprotected LM disease with paclitaxel-eluting stents. METHODS AND RESULTS: A total of 291 patients were prospectively included from 4 centers. Acute myocardial infarction and cardiogenic shock were the only exclusion criteria. Patients were 69+/-11 years old, 29% were diabetic, and 25% had 3-vessel disease. For distal LM lesions (78%), the provisional side-branch T-stenting approach was used in 92% of cases and final kissing balloon inflation in 97%. Angiographic success was obtained in 99.7% of cases. At 2-year follow-up, the total cardiac death rate was 5.4% (1 EuroSCORE point was associated with a 15% [95% confidence interval 2.9% to 28.2%, P=0.013] higher risk of cardiac death), target-lesion revascularization was 8.7%, and incidence of Q-wave or non-Q-wave myocardial infarction was 0.9% and 3.1%, respectively. The combined end point occurred in 15.8% of cases and stroke in 0.7%. The incidence of definite and probable LM stent thrombosis was 0.7%, whereas the incidence of any stent thrombosis was 3.8%, with a higher risk in patients with side-branch stenting in the presence of LM bifurcation lesions (hazard ratio 9.6, 95% confidence interval 1.2 to 77.7, P=0.035). CONCLUSIONS: Unprotected LM stenting with paclitaxel-eluting stents, with a strategy of provisional side-branch T-stenting for distal lesions, provides excellent acute angiographic results and good mid-term clinical outcomes, with a 15.8% rate of major adverse cardiac events at 2-year follow-up.

Increased prevalence of hyperhomocysteinemia in cervical artery dissection causing stroke: a case-control study

BACKGROUND: Spontaneous cervical artery dissection (sCAD) is a nonatherosclerotic vascular disease of unknown etiology. Mild elevation of total plasma homocysteine (tHcy) levels may be a risk factor for sCAD, but the precise mechanism remains unknown. On the other hand, mild hyperhomocysteinemia is also associated with ischemic stroke related to atherothrombotic or small artery disease. We undertook a case-control study to compare the prevalence of mild hyperhomocysteinemia and tHcy levels between patients with a first ischemic stroke due to sCAD and healthy volunteers, as well as patients with a first ischemic stroke due to atherothrombotic or small artery disease. METHODS: Fasting tHcy levels were determined in 346 consecutive patients with a first ischemic stroke due to sCAD (n = 86) and atherothrombotic or small artery disease (n = 260) within 24 h after the onset of symptoms, and in 100 healthy volunteers. RESULTS: Mild hyperhomocysteinemia was more prevalent in patients with sCAD causing ischemic stroke (n = 33, 38%) than in healthy volunteers (n = 23, 23%; p = 0.034), and less prevalent than in patients with ischemic stroke due to atherothrombotic or small artery disease (n = 149, 57%; p = 0.001). Mean fasting tHcy levels of patients with ischemic stroke caused by sCAD showed a trend to be higher (11.4 +/- 3.8 micromol/l) than those of healthy volunteers (10.2 +/- 3.0 micromol/l, p = 0.61), but were lower than those of patients with stroke due to atherothrombotic or small artery disease (13.6 +/- 6.6 micromol/l, p = 0.002). CONCLUSION: Our results suggest that mild hyperhomocysteinemia may be a risk factor for sCAD causing ischemic stroke, but further studies are needed to identify a possible mechanism. This study confirms the association of hyperhomocysteinemia with ischemic stroke due to atherothrombotic or small artery disease.