Supernumerary right coronary artery

A rare case of a patient with supernumerary right coronary artery in whom the two vessels arose from the right coronary sinus from two separate ostia adjacent to each other is presented. The smaller vessel gave off the sinoatrial nodal branch and the posterior descending artery whereas the larger one gave off the conus branch, the right ventricular branches, and continued as acute marginal branch. This is the first case report in the English literature.     

Difficulties in the use of electrocardiographic criteria for the differential diagnosis of left bundle branch block pattern tachycardia in patients with a structurally normal heart.

In patients with left bundle branch block pattern tachycardia, electrocardiographic criteria, based on leads V1, V2 and V6, have been shown to be effective for the diagnosis of ventricular tachycardia in patients with a previous myocardial infarct. To test these criteria on a wider population, we studied 53 consecutive patients with left bundle branch block pattern tachycardia. Seventeen patients had supraventricular tachycardia and 36 had ventricular tachycardia, 18 with a previous myocardial infarction, two with cardiomyopathy, and 16 with a normal heart. The sensitivity for the diagnosis of ventricular tachycardia in patients with a previous myocardial infarct of the combined criteria was 100% but was only 50% for the other patients, which was not significantly different from the patients with supraventricular tachycardia (29%). Two other criteria, right axis shift in tachycardia and ventricular ectopics during sinus rhythm with the same morphology as the tachycardia, were only seen in patients with ventricular tachycardia, and combined with the other criteria allowed the correct identification of 35/36 patients with ventricular tachycardia. To conclude, the electrocardiographic criteria based on leads V1, V2 and V6 are not sensitive for the diagnosis of a ventricular origin of left bundle branch block pattern tachycardia in patients with a normal heart and additional criteria are required for the diagnosis in these patients.     

Optimal Fluoroscopic Projections of Coronary Ostia and Bifurcations Defined by Computed Tomographic Coronary Angiography

ObjectivesThe aim of this study was to define the optimal fluoroscopic viewing angles of both coronary ostia and important coronary bifurcations by using 3-dimensional multislice computed tomographic data.BackgroundOptimal fluoroscopic projections are crucial for coronary imaging and interventions. Historically, coronary fluoroscopic viewing angles were derived empirically from experienced operators.MethodsIn this analysis, 100 consecutive patients who underwent computed tomographic coronary angiography (CTCA) for suspected coronary artery disease were studied. A CTCA-based method is described to define optimal viewing angles of both coronary ostia and important coronary bifurcations to guide percutaneous coronary interventions.ResultsThe average optimal viewing angle for ostial left main stenting was left anterior oblique (LAO) 37°, cranial (CRA) 22° (95% confidence interval [CI]: LAO 33° to 40°, CRA 19° to 25°) and for ostial right coronary stenting was LAO 79°, CRA 41° (95% CI: LAO 74° to 84°, CRA 37° to 45°). Estimated mean optimal viewing angles for bifurcation stenting were as follows: left main: LAO 0°, caudal (CAU) 49° (95% CI: right anterior oblique [RAO] 8° to LAO 8°, CAU 43° to 54°); left anterior descending with first diagonal branch: LAO 11°, CRA 71° (95% CI: RAO 6° to LAO 27°, CRA 66° to 77°); left circumflex bifurcation with first marginal branch: LAO 24°, CAU 33° (95% CI: LAO 15° to 33°, CAU 25° to 41°); and posterior descending artery and posterolateral branch: LAO 44°, CRA 34° (95% CI: LAO 35° to 52°, CRA 27° to 41°).ConclusionsCTCA can suggest optimal fluoroscopic viewing angles of coronary artery ostia and bifurcations. As the frequency of use of diagnostic CTCA increases in the future, it has the potential to provide additional information for planning and guiding percutaneous coronary intervention procedures.     

The Utility of Rapid Atrial Pacing Immediately Post-TAVR to Predict the Need for Pacemaker Implantation

ObjectivesThe aim of this study was to determine the utility of rapid atrial pacing immediately after transcatheter aortic valve replacement (TAVR) to predict the need for permanent pacemaker implantation (PPI).BackgroundRisk stratification for patients without high-grade atrioventricular block (AVB) after TAVR is imprecise and based on anatomic considerations, electrocardiographic characteristics, and clinical suspicion. A more reliable assessment is necessary to minimize inpatient rhythm monitoring and/or reduce unnecessary PPI.MethodsConsecutive patients undergoing TAVR at 2 centers were included. After valve implantation in patients without pacemakers who did not have complete heart block or atrial fibrillation, the temporary pacemaker was withdrawn from the right ventricle and placed in the right atrium. Rapid atrial pacing was performed from 70 to 120 beats/min, and patients were assessed for the development of Wenckebach AVB. Patients were then followed for clinical outcomes, including PPI.ResultsA total of 284 patients were included. Of these, 130 (45.8%) developed Wenckebach AVB. There was a higher rate of PPI within 30 days of TAVR among the patients who developed Wenckebach AVB (13.1% vs. 1.3%; p < 0.001), with a negative predictive value for PPI in the group without Wenckebach AVB of 98.7%. A greater percentage of patients receiving self-expanding valves required PPI than those receiving a balloon-expandable valves (15.9% vs. 3.7%; p = 0.001), though these rates were still relatively low among patients who did not develop Wenckebach AVB (2.9% and 0.8%).ConclusionsAtrial pacing post-TAVR is easily performed and can help identify patients who may benefit from extended rhythm monitoring. Patients who did not develop pacing-induced Wenckebach AVB demonstrated an extremely low likelihood of PPI.     

Prognostic value of electrophysiologic investigations in Brugada syndrome

INTRODUCTION: The prognostic value of electrophysiologic investigations in individuals with Brugada syndrome is unclear. Previous studies failed to determine its value because of a limited number of patients or lack of events during follow-up. We present data on the prognostic value of electrophysiologic studies in the largest cohort ever collected of patients with Brugada syndrome. METHODS AND RESULTS: Two hundred fifty-two individuals with an ECG diagnostic of Brugada syndrome were studied electrophysiologically. The diagnosis was made because of a classic ECG with a coved-type ST segment elevation in precordial leads V1 to V3. Of the 252 individuals, 116 had previously developed spontaneous symptoms (syncope or aborted sudden cardiac death) and 136 were asymptomatic at the time of diagnosis. A sustained ventricular arrhythmia was induced in 130 patients (51%). Symptomatic patients were more frequently inducible (73%) than asymptomatic individuals (33%) (P = 0.0001). Fifty-two individuals (21%) developed an arrhythmic event during a mean follow-up of 34 +/- 40 months. Inducibility was a powerful predictor of arrhythmic events during follow-up both in symptomatic and asymptomatic individuals. Overall accuracy of programmed ventricular stimulation to predict outcome was 67%. Overall accuracy in asymptomatic individuals was 70.5%, with a 99% negative predictive value. Overall accuracy in symptomatic patients was 62%, with only a 4.5% false-negative rate. No significant differences were found in the duration of the H-V interval during sinus rhythm between symptomatic or asymptomatic individuals. However, the H-V interval was significantly longer in the asymptomatic individuals who became symptomatic during follow-up compared with those who did not develop symptoms (59 +/- 8 msec vs 48 +/- 11 msec, respectively; P = 0.04). CONCLUSION: Inducibility of sustained ventricular arrhythmias is a good predictor of outcome in Brugada syndrome. In asymptomatic individuals, a prolonged H-V interval during sinus rhythm is associated with a higher risk of developing arrhythmic events during follow-up. Symptomatic patients require protective treatment even when they are not inducible. Asymptomatic patients can be reassured if they are noninducible.     

Intronic sequence elements impede exon ligation and trigger a discard pathway that yields functional telomerase RNA in fission yeast

The fission yeast telomerase RNA (TER1) precursor harbors an intron immediately downstream from its mature 3′ end. Unlike most introns, which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transesterification reactions, TER1 only undergoes the first cleavage reaction during telomerase RNA maturation. The mechanism underlying spliceosome-mediated 3′ end processing has remained unclear. We now demonstrate that a strong branch site (BS), a long distance to the 3′ splice site (3′ SS), and a weak polypyrimidine (Py) tract act synergistically to attenuate the transition from the first to the second step of splicing. The observation that a strong BS antagonizes the second step of splicing in the context of TER1 suggests that the BS–U2 snRNA interaction is disrupted after the first step and thus much earlier than previously thought. The slow transition from first to second step triggers the Prp22 DExD/H-box helicase-dependent rejection of the cleaved products and Prp43-dependent “discard” of the splicing intermediates. Our findings explain how the spliceosome can function in 3′ end processing and provide new insights into the mechanism of splicing.     

离断大鼠迷走神经肝支对血糖血脂水平的影响及其与mTOR表达水平的关系

目的　探讨离断大鼠迷走神经肝支对血糖、血脂水平的影响及其与mTOR表达水平的关系,为糖脂代谢神经调节机制研究提供实验依据。 方法　建立离断迷走神经肝支大鼠模型作为实验组,另设迷走神经肝支探查的假手术组和不作任何处理的对照组,术后每两周检测大鼠血糖、血脂、胰岛素和皮质醇水平、肝和骨骼肌组织的糖原含量以及mTOR的表达水平。 结果　实验组大鼠与对照组大鼠相比,术后2周胰岛素水平升高、肝糖原含量增多、血糖水平降低（P<0.05）;术后6周,肝、骨骼肌组织mTOR表达增多、肝糖原及骨骼肌糖原含量降低、血糖水平增高、甘油三酯水平增高,高密度脂蛋白水平降低（P<0.05）。假手术组和对照组大鼠各项指标各时间点无明显差异（P>0.05）。 结论　离断大鼠迷走神经肝支可导致糖脂代谢以及糖原含量异常,其机制可能与胰岛素水平变化以及肝、骨骼肌mTOR表达水平升高有关。     

An Anatomical Study to Demonstrate the Proximity of Kirschner Wires to Structures at Risk in Percutaneous Pinning of Distal Radius Fractures

Distal radius fractures are often treated using percutaneous Kirschner wires (K-wires). The sensory nerves in this area, extensor tendons, radial artery and cephalic vein are at risk of injury in this procedure. We undertook a cadaveric investigation to identify probability of damage to these ‘at risk’ structures by measuring their distances in relation to standard K-wire sites. Nine upper limbs from six formalin-preserved cadavers were studied. Four K-wires were placed percutaneously simulating fixation of a distal radius fracture. Careful dissection was done preserving the original position of neurovascular and tendinous structures. Distances to relevant soft-tissue structures from each K-wire were measured using an electronic digital caliper. Distance of superficial nerves from radial styloid and Lister’s tubercle was measured to determine their ‘safe distance’ from these fixed landmarks. None of the superficial nerves were injured by a K-wire. Cephalic vein had been pierced on 4 occasions (4/18) and extensor tendons on 3 occasions (3/18). Wilcoxon signed-rank test was used to compare distance of the superficial nerves from radial styloid and Lister tubercle, and the latter was found to be the safer option. This study highlights the inherent danger in percutaneous K-wire fixation of wrist fractures. Limited size of the area, where K-wires can be positioned, and anatomic variations of neurovascular structures pose obstacles in developing guidelines for reducing risk of injury. We advocate use of mini-open approach and guiding devices to avert complications of inadvertent impalement and damage to these structures.     

A genetic method for dating ancient genomes provides a direct estimate of human generation interval in the last 45,000 years

The study of human evolution has been revolutionized by inferences from ancient DNA analyses. Key to these studies is the reliable estimation of the age of ancient specimens. High-resolution age estimates can often be obtained using radiocarbon dating, and, while precise and powerful, this method has some biases, making it of interest to directly use genetic data to infer a date for samples that have been sequenced. Here, we report a genetic method that uses the recombination clock. The idea is that an ancient genome has evolved less than the genomes of present-day individuals and thus has experienced fewer recombination events since the common ancestor. To implement this idea, we take advantage of the insight that all non-Africans have a common heritage of Neanderthal gene flow into their ancestors. Thus, we can estimate the date since Neanderthal admixture for present-day and ancient samples simultaneously and use the difference as a direct estimate of the ancient specimen’s age. We apply our method to date five Upper Paleolithic Eurasian genomes with radiocarbon dates between 12,000 and 45,000 y ago and show an excellent correlation of the genetic and ¹⁴C dates. By considering the slope of the correlation between the genetic dates, which are in units of generations, and the ¹⁴C dates, which are in units of years, we infer that the mean generation interval in humans over this period has been 26–30 y. Extensions of this methodology that use older shared events may be applicable for dating beyond the radiocarbon frontier.Ancient DNA analyses have transformed research into human evolutionary history, making it possible to directly observe genetic variation patterns that existed in the past, instead of having to infer them retrospectively (1). To interpret findings from an ancient specimen, it is important to have an accurate estimate of its age. The current gold standard is radiocarbon dating, which is applicable for estimating dates for samples up to 50,000 y old (2). This method is based on the principle that, when a living organism dies, the existing ¹⁴C starts decaying to ¹⁴N with a half-life of ∼5,730 y (3). By measuring the ratio of ¹⁴C to ¹²C in the sample and assuming that the starting ratio of carbon isotopes is the same everywhere in the biosphere, the age of the sample is inferred. A complication is that carbon isotope ratios vary among carbon reservoirs (e.g., marine, freshwater, atmosphere) and over time. Thus, ¹⁴C dates must be converted to calendar years using calibration curves based on other sources, including annual tree rings (dendrochronology) or uranium-series dating of coral (2). Such calibrations, however, may not fully capture the variation in atmospheric carbon. In addition, contamination of a sample by modern carbon, introduced during burial or by handling afterwards, can make a sample seem younger than it actually is (2). The problem is particularly acute for samples that antedate 30,000 y ago because they retain very little original ¹⁴C.Here, we describe a genetic approach for dating ancient samples, applicable in cases where DNA sequence data are available, as is becoming increasingly common (1). This method relies on the insight that an ancient genome has experienced fewer generations of evolution compared with the genomes of its living (i.e., extant) relatives. Because recombination occurs at an approximately constant rate per generation, the accumulated number of recombination events provides a molecular clock for the time elapsed or, in the case of an ancient sample, the number of missing generations since it ceased to evolve. This idea is referred to as “branch shortening” and estimates of missing evolution can be translated into absolute time in years by using an estimate of the mean age of reproduction (generation interval) or an independent calibration point such as human–ape divergence time.Branch shortening has been used in studies of population history, for inferring mutation rates, and for establishing time scales for phylogenic trees in humans and other species (4, 5). It was first applied for dating ancient samples on a genome-wide scale by Meyer et al. (6), who used the mutation clock (instead of the recombination clock as proposed here) to estimate the age of the Denisova finger bone, which is probably older than 50,000 y, and has not been successfully radiocarbon dated (6). Specifically, the authors compared the divergence between the Denisova and extant humans and calibrated the branch shortening relative to human–chimpanzee (HC) divergence time. The use of ape divergence time for calibration, however, relies on estimates of mutation rate that are uncertain (7). In particular, recent pedigree studies have yielded a yearly mutation rate that is approximately twofold lower than the one obtained from phylogenetic methods (7). In addition, comparison with HC divergence relies on branch-shortening estimates that are small relative to the total divergence of millions of years, so that even very low error rates in allele detection can bias estimates. These issues lead to substantial uncertainty in estimated age of the ancient samples, making this approach impractical for dating specimens that are tens of thousands of years old, a time period that encompasses the vast majority of ancient human samples sequenced to date.Given the challenges associated with the use of the mutation clock, here we explore the possibility of using a molecular clock based on the accumulation of crossover events (the recombination clock), which is measured with high precision in humans (8). In addition, instead of using a distant outgroup, such as chimpanzees, we rely on a more recent shared event that has affected both extant and ancient modern humans and is therefore a more reliable fixed point on which to base the dating. Previous studies have documented that most non-Africans derive 1–4% ancestry from Neanderthals from an admixture event that occurred ∼37,000–86,000 y before present (yBP) (9, 10), with some analyses proposing a second event (around the same time) into the ancestors of East Asians (11, 12). Because the vast majority of ancient samples sequenced to date were discovered in Eurasia (with estimated ages of ∼2,000–45,000 yBP), postdate the Neanderthal admixture, and show evidence of Neanderthal ancestry, we used the Neanderthal gene flow as the shared event.The idea of our method is to estimate the date of Neanderthal gene flow separately for the extant and ancient genomes. Because the ancient sample is closer in time to the shared Neanderthal admixture event, we expect that the inferred dates of Neanderthal admixture will be more recent in ancient genomes (by an amount that is directly determined by the sample’s age) compared with the dates in the extant genomes. The difference in the dates thus provides an estimate of the amount of missing evolution: that is, the age of the ancient sample. An illustration of the idea is shown in SI Appendix, Fig. S1. An assumption in our approach is that the Neanderthal admixture into the ancestors of modern humans occurred approximately at the same time and that the same interbreeding events contributed to the ancestry of all of the non-African samples being compared. Deviations from this model could lead to incorrect age estimates. Our method is not applicable for dating genomes that do not have substantial Neanderthal ancestry, such as sub-Saharan African genomes.To date the Neanderthal admixture event, we used the insight that gene flow between genetically distinct populations, such as Neanderthals and modern humans, introduces blocks of archaic ancestry into the modern human background that break down at an approximately constant rate per generation as crossovers occur (13–15). Thus, by jointly modeling the decay of Neanderthal ancestry and recombination rates across the genome, we can estimate the date of Neanderthal gene flow, measured in units of generations. Similar ideas have been used to estimate the time of admixture events between contemporary human populations (14–16), as well as between Eurasians and Neanderthals (9, 17). An important feature of our method is that it is expected to give more precise results for samples that are older because these samples are closer in time to the Neanderthal introgression event, thus it is easier to accurately estimate the time of the admixture event for them. Thus, unlike ¹⁴C dating, the genetic approach becomes more reliable with age and, in that regard, complements ¹⁴C dating.     

Acute anterior wall myocardial infarction entailing st-segment elevation in lead v1: Electrocardiographic and angiographic correlations

Background: The correlation between ST elevation in lead V₁ during anterior wall acute myocardial infaction (AMI) and the culprit lesion site in the left anterior descending (LAD) coronary artery is poor. Hypothesis: The study was undertaken to assess the electrocardiographic (ECG) characteristics and angiographic significance of ST-segment elevation in lead V¹ during anterior wall acute myocardial infarction (AMI). Methods: Data from 115 patients with anterior wall AMI, who underwent coronary angiography within 14 days of hospitalization, were studied. The admission 12-lead ECG was examined and the coronary angiogram was evaluated for the nature of the conal branch of the right coronary artery (RCA) and for the culprit lesion site in the left anterior descending (LAD) coronary artery. Results: Mean ST-segment deviation and the frequency of patients with ST-segment elevation > 0.1 mV were significantly lower in lead V i than in lead V2 (0.136 $$ 0.111 mV vs. 0.421 $$ 0.260 mV, and 37 vs. 96%, for leads Vi and Vi, respectively). A small conal branch not reaching the interventricular septum (IVS) was more prevalent among patients with ST-segnicni elevation >0.1 mV in lead Vi (67%), whereas a large conal branch was more prevalent in patients with ST-segment deviation (1 mV in that lead (83%, p<0.001). No relation was found between ST-segment deviation in lead V i during anterior wall AMI and the culprit lesion site in the LAD. Conclusion: ST-segment elevation in lead V₁ during first anterior wall AMI was found in one third of the patients, and its magnitude was lower than that in the other precordial leads. ST-segment elevation in lead V₁ favors the presence of a small conal branch of the RCA that does not reach the IVS.