Cusp Symmetry and Coronary Ostial Eccentricity and its Impact on Coronary Access Following TAVR

ObjectivesThe aim of this study was to assess cusp symmetry and coronary ostial eccentricity and its impact on coronary access following transcatheter aortic valve replacement (TAVR) using a patient-specific commissural alignment implantation technique.BackgroundTAVR implantation techniques to obtain neocommissural alignment have been introduced. The impact of cusp symmetry and coronary ostial eccentricity on coronary access after TAVR remains unknown.MethodsCardiac computed tomographic scans from 200 tricuspid aortic valves (TAVs) and 200 type 1 bicuspid aortic valves (BAVs) were studied. Cusp symmetry and coronary ostial eccentricity were assessed. In addition, the right coronary cusp/left coronary cusp and right coronary artery (RCA)/left coronary artery (LCA) ostia overlap views were calculated and compared.ResultsSevere cusp asymmetry (>135°) was more frequent in BAVs (52.5%) than in TAVs (2.5%) (P < 0.001), with the noncoronary cusp being the most common dominant cusp. The RCA ostium was found to be more often eccentric (>20°) than the LCA ostium (28% vs 6%, respectively; P < 0.001). Considering the right/left cusp overlap view, there was <20° deviation between the right coronary cusp–left coronary cusp centered line and the RCA-LCA centered line in 95% of all patients (TAV, 97%; BAV, 93%). The right/left cusp and coronary ostia overlap view differed by <10° and <20° fluoroscopic angulation in 75% and 98% of all cases, respectively.ConclusionsUsing the right/left cusp overlap view to obtain commissural alignment in TAVR is also an effective approach to implant one of the transcatheter heart valve commissures in the near center between both coronary ostia in most TAVs and type 1 BAVs. Preprocedural CT assessment remains crucial to assess cusp symmetry and coronary ostial eccentricity.     

Isolation and characterization of beta 1-adrenergic receptors from adult, rat cardiac myocytes

The beta-receptors were isolated from rat cardiac myocytes and characterized. Isolated myocytes were prepared from adult rat hearts and characterized for viability. Membrane proteins were solubilized from myocytes with 1% Triton X-102. The solubilized membrane proteins were fractionated by DEAE-Sephacel ion exchange column chromatography. Two major protein peaks were obtained. The second protein peak sample was found to contain beta-receptors to which 125I-15-(4'-azido-3'-iodobenzyl)-carazolol (125I-ABC) was specifically bound. This sample was labeled covalently with 125I-ABC by UV irradiation. The radiolabeled sample was applied to a Sepharose CL-6B gel column. Two radiolabeled protein peaks, one with a molecular weight of approximately 570,000 and the other with a molecular weight of approximately 95,000 were found. When the 570,000-dalton complex was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions, it was dissociated into a component with a molecular weight of 66,000. The 95,000-dalton complex was dissociated into a 58,000-dalton component upon SDS-PAGE under reducing conditions. An excess amount of isoproterenol and propranolol decreased photolabeling of the beta-receptors with 125I-ABC by 60% and 40%, respectively.     

The applicability of the signal averaging technique in clinical cardiology

Summary: Since 1963 the signal averaging technique has been applied to improve the signal to noise ratio in highly amplified EKG registrations. Based on the experiences from the literature and the authors own laboratory, the applications of the signal averaging technique in clinical cardiology are reviewed: extraction and analysis of the fetal EKG and P-wave variations, His bundle electro-grams from the body surface (recovery rate 33–100% of cases), ventricular delayed depolarizations within the ST segment of the surface EKG (recovery rate, 40–90% of cases, depending on patient groups investigated), preatrial activity (sinus nodal potentials) from intra-cardiac (recovery rate, 80–90% of individuals), or surface EKGs (recovery rate, 60% of patients), analysis of frequency components of surface EKG-QRS complexes in patients with previous myocardial infarctions, and detection of low amplitude diastolic signals from surface phonocardiogram (recovery rate, 80% of cases). At present, advantages and limitations of the signal averaging technique may be appraised as follows: (1) sinus nodal potentials: S-A conduction times may be more reliable than those obtained by the extra-stimulus technique, since with averaging they are recorded during undisturbed sinus rhythm; direct recordings of changing S-A blocks may be impossible due to the summation process; validation of sinus nodal potentials in man necessary, (2) A-V nodal potentials: demonstration of true A-V nodal rhythm rather than His bundle rhythm; possibly direct identification of abnormal pathways in A-V nodal tachycardias; direct recordings of single A-V nodal blocks impossible due to summation process; (3) surface His bundle potentials: follow-up or screening of patients with A-V nodal and particularly His-Pur-kinje-system blocks; monitoring of antiarrhythmic drug therapy; atrial overlap in one-third of cases; direct identification of higher degree A-V nodal blocks impossible due to summation process (future developments may overcome this problem); (4) ventricular delayed depolarizations: possible identification of patients at high risk of sudden cardiac death; follow-up of therapeutic measures like antiarrhythmic drug therapy or cardiac surgery (bypass grafting, aneurysmectomy); validation of delayed depolarizations from body surface by direct intracardiac and/or epicardial mapping necessary.     

Haemodynamic effects of frusemide and its influence on repetitive rapid volume loading in acute myocardial infarction

The haemodynamic effects of intravenous frusemide (1 mg/kg)were studied in 22 male patients with left ventricular failurefollowing acute myocardial infarction. Radiographic pulmonaryoedema was present in all patients and their average left heartfilling pressure was 20 mmHg. Bolus injection of the drug wasfollowed by immediate increases in systemic arterial pressure(P < 0.05) and heart rate (<0.05); these declined to pre-injectionvalues after 60 min. Following frusemide there were progressivereductions in left heart filling pressure (P < 0.01), thermodilutioncardiac output (P < 0.01) and stroke volume (P < 0.05)and a progressive increase in the derived systemic vascularresistance (P < 0.05). There was an average diuresis of 860ml during the 90 min following the frusemide injection. Theinfluence of frusemide on left ventricular performance was studiedby comparing the circulatory effects of passive leg raisingin the control period with those at 30, 60 and 90 min afterthe drug. In the control period this manoeuvre increased leftheart filling pressure, but not heart rate, cardiac output,stroke volume or systemic vascular resistance. Ninety minutesafter frusemide, but not before, passive leg raising resultedin a significant increase in cardiac output (P < 0.01) andstroke volume at a similar increment in filling pressure anda significant reduction in the systemic vascular resistance(P <0.05). These circulatory actions of intravenous frusemideare compatible with initial arteriolar constriction and venodilatationfollowed by depletion of blood volume with subsequent changein left ventricular pumping performance.     

TGF-β1 enhances cardiomyogenic differentiation of skeletal muscle-derived adult primitive cells

The optimal medium for cardiac differentiation of adult primitive cells remains to be established. We quantitatively compared the efficacy of IGF-1, dynorphin B, insulin, oxytocin, bFGF, and TGF-β1 in inducing cardiomyogenic differentiation. Adult mouse skeletal muscle-derived Sca1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells were cultured in basic medium (BM; DMEM, FBS, IGF-1, dynorphin B) alone and BM supplemented with insulin, oxytocin, bFGF, or TGF-β1. Cardiac differentiation was evaluated by the expression of cardiac-specific markers at the mRNA (qRT-PCR) and protein (immunocytochemistry) levels. BM+TGF-β1 upregulated mRNA expression of Nkx2.5 and GATA-4 after 4 days and Myl2 after 9 days. After 30 days, BM+TGF-β1 induced the greatest extent of cardiac differentiation (by morphology and expression of cardiac markers) in SM- cells. We conclude that TGF-β1 enhances cardiomyogenic differentiation in skeletal muscle-derived adult primitive cells. This strategy may be utilized to induce cardiac differentiation as well as to examine the cardiomyogenic potential of adult tissue-derived stem/progenitor cells. Electronic supplementary material  The online version of this article (DOI:) contains supplementary material, which is available to authorized users. Returned for 1. Revision: 8 January 2008 1. Revision received: 8 April 2008 Ahmed Abdel-Latif and Ewa K. Zuba-Surma contributed equally to this work.     

Increased thromboxane production in women with a history of venous thromboembolic event: effect of heparins

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1alpha) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (+/-SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44.0 +/- 4.1 versus 19.0 +/- 3.6 ng/mmol creatinine, P < 0.001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25.2 +/- 3.5 versus 13.6 +/- 2.1 ng/mmol creatinine, P < 0.01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins.     

优化AV间期和VV间期对提高心脏再同步治疗疗效的评价

心脏再同步治疗(CRT)作为一种新治疗心力衰竭的方法,疗效确切,但是心脏再同步一心力衰竭研究(CARE-HF)证实仍然有20%～30%患者对CRT治疗无反应.目前认为提高CRT疗效除了严格适应证选择、左室电极的正确放置外,术后进行房室问期(AV间期)以及心室同步(VV间期)优化是一项重要措施.迄今为止,已经提出很多指导优化程控的方法,如心电图、超声心动图、核素心室显像、磁共振描记成像等.就心电图而言,心电图简单而且在理论上有助于CRT的优化程控,但是忽略了心肌各部位之间的电机械延迟;同心电图相比,超声心动图指标有重要的实践意义,是CRT术后优化程控的有效方法.但是CRT术后优化程控仍然面临重大挑战,最佳AV存在个体差异,而且随着心率的变化而改变,因此个体化的动态优化程控是今后发展的方向.     

The Effect of Computerized Physician Order Entry with Clinical Decision Support on the Rates of Adverse Drug Events: A Systematic Review

Context Computerized physician order entry (CPOE) with clinical decision support (CDS) has been promoted as an effective strategy to prevent the development of a drug injury defined as an adverse drug event (ADE). Objective To systematically review studies evaluating the effects of CPOE with CDS on the development of an ADE as an outcome measure. Data Sources PUBMED versions of MEDLINE (from inception through March 2007) were searched to identify relevant studies. Reference lists of included studies were also searched. Methods We searched for original investigations, randomized and nonrandomized clinical trials, and observational studies that evaluated the effect of CPOE with CDS on the rates of ADEs. The studies identified were assessed to determine the type of computer system used, drug categories being evaluated, types of ADEs measured, and clinical outcomes assessed. Results Of the 543 citations identified, 10 studies met our inclusion criteria. These studies were grouped into categories based on their setting: hospital or ambulatory; no studies related to the long-term care setting were identified. CPOE with CDS contributed to a statistically significant (P ≤ .05) decrease in ADEs in 5 (50.0%) of the 10 studies. Four studies (40.0%) reported a nonstatistically significant reduction in ADE rates, and 1 study (10.0%) demonstrated no change in ADE rates. Conclusions Few studies have measured the effect of CPOE with CDS on the rates of ADEs, and none were randomized controlled trials. Further research is needed to evaluate the efficacy of CPOE with CDS across the various clinical settings.     

冠心病心室晚电位与冠状动脉病变的关系

为观察心室晚电位（ＶＬＰ）、心律失常事件（ＡＥ）与冠状动脉病变的关系，对１４５例冠心病患者（心绞痛５５例、陈旧性心肌梗死９０例）进行信号平均心电图的定性分析和２４小时Ｈｏｌｔｅｒ监测，并同期进行冠状动脉造影，并长期随访观察。１１９例（失访２６例）随访１４．１±７．１（４～３６）个月，发生ＡＥ７例。ＶＬＰ阳性者ＡＥ发生率２５％（４／１６），明显高于ＶＬＰ阴性者ＡＥ的发生率２．９％（３／１０３），Ｐ＜０．００１；ＶＬＰ、ＡＥ与冠状动脉病变血管的支数和狭窄程度之间均无明显关系（Ｐ均＞０．０５）。结果提示ＶＬＰ与ＡＥ密切相关，但ＶＬＰ、ＡＥ与冠状动脉病变的范围和程度无明显关系。     

Changes in DNA content,number of nuclei and cellular dimensions of young rat atrial myocytes in response to left coronary artery ligation

Studies of enzymatically isolated myocytes from atria of young male Sprague-Dawley rats at 11 days after left coronary artery ligation show that a major response of atrial myocytes to ventricular infarction is binucleation. In sham-operated animals, 23.2% of left and 15.5% of right atrial myocytes were binucleated, compared to 77.8% of left and 40.5% of right atrial myocytes of infarcted animals. Examination of 150 g and 250 g unoperated control animals indicate that this response is occurring at a time when a small but significant amount of binucleation is also occurring as a normal part of growth. Using a Feulgen-acriflavine-SO₂ method for cytofluorometry, a significant increase in ploidy was seen in left atrial myocytes of infarcted animals over those of sham or control animals. The number of left atrial myocytes in infarcted animals having a ploidy level above 3C was 10.8% above sham values. The mean length of binucleated myocytes of left atrium was significantly greater in infarcted animals (119.8 μm) than in sham-operated animals (97 μm) and the mean length of mononucleated myocytes was greater in infarcted animals (104.1 μm) than in sham-operated animals (77 μm). Thus, cardiac myocytes are capable of a substantial response to a stressful situation by increases in cell length, number of nuclei and ploidy. Study of a model system such as the rat atrium may yield an understanding of the mechanisms involved in the induction of these nuclear changes.