Refining Our Understanding of the Flow Through Coronary Artery Branches; Revisiting Murray's Law in Human Epicardial Coronary Arteries

Background: Quantification of coronary blood flow is used to evaluate coronary artery disease, but our understanding of flow through branched systems is poor. Murray’s law defines coronary morphometric scaling, the relationship between flow (Q) and vessel diameter (D) and is the basis for minimum lumen area targets when intervening on bifurcation lesions. Murray’s original law (Q α D(P)) dictates that the exponent (P) is 3.0, whilst constant blood velocity throughout the system would suggest an exponent of 2.0. In human coronary arteries, the value of Murray’s exponent remains unknown. Aim: To establish the exponent in Murray’s power law relationship that best reproduces coronary blood flows (Q) and microvascular resistances (Rmicro) in a bifurcating coronary tree. Methods and Results: We screened 48 cases, and were able to evaluate inlet Q and Rmicro in 27 branched coronary arteries, taken from 20 patients, using a novel computational fluid dynamics (CFD) model which reconstructs 3D coronary anatomy from angiography and uses pressure-wire measurements to compute Q and Rmicro distribution in the main- and side-branches. Outputs were validated against invasive measurements using a Rayflow™ catheter. A Murray’s power law exponent of 2.15 produced the strongest correlation and closest agreement with inlet Q (zero bias, r = 0.47, p = 0.006) and an exponent of 2.38 produced the strongest correlation and closest agreement with Rmicro (zero bias, r = 0.66, p = 0.0001). Conclusions: The optimal power law exponents for Q and Rmicro were not 3.0, as dictated by Murray’s Law, but 2.15 and 2.38 respectively. These data will be useful in assessing patient-specific coronary physiology and tailoring revascularisation decisions

Validation of a novel numerical model to predict regionalized blood flow in the coronary arteries

Aims: Ischaemic heart disease results from insufficient coronary blood flow. Direct measurement of absolute flow (mL/min) is feasible, but has not entered routine clinical practice in most catheterization laboratories. Interventional cardiologists, therefore, rely on surrogate markers of flow. Recently, we described a computational fluid dynamics (CFD) method for predicting flow that differentiates inlet, side branch, and outlet flows during angiography. In the current study, we evaluate a new method that regionalizes flow along the length of the artery. Methods and results: Three-dimensional coronary anatomy was reconstructed from angiograms from 20 patients with chronic coronary syndrome. All flows were computed using CFD by applying the pressure gradient to the reconstructed geometry. Side branch flow was modelled as a porous wall boundary. Side branch flow magnitude was based on morphometric scaling laws with two models: a homogeneous model with flow loss along the entire arterial length; and a regionalized model with flow proportional to local taper. Flow results were validated against invasive measurements of flow by continuous infusion thermodilution (Coroventis™, Abbott). Both methods quantified flow relative to the invasive measures: homogeneous (r 0.47, P 0.006; zero bias; 95% CI -168 to +168 mL/min); regionalized method (r 0.43, P 0.013; zero bias; 95% CI -175 to +175 mL/min). Conclusion: During angiography and pressure wire assessment, coronary flow can now be regionalized and differentiated at the inlet, outlet, and side branches. The effect of epicardial disease on agreement suggests the model may be best targeted at cases with a stenosis close to side branches.</p

Modified magnetic anisotropy at LaCoO_(3)/La_(0.7)Sr_(0.3)MnO_(3) interfaces

Controlling magnetic anisotropy is an important objective towards engineering novel magnetic device concepts in oxide electronics. In thin film manganites, magnetic anisotropy is weak and it is primarily determined by the substrate, through induced structural distortions resulting from epitaxial mismatch strain. On the other hand, in cobaltites, with a stronger spin orbit interaction, magnetic anisotropy is typically much stronger. In this paper, we show that interfacing La0.7Sr0.3MnO3 (LSMO) with an ultrathin LaCoO3 (LCO) layer drastically modifies the magnetic anisotropy of the manganite, making it independent of the substrate and closer to the magnetic isotropy characterizing its rhombohedral structure. Ferromagnetic resonance measurements evidence a tendency of manganite magnetic moments to point out-of-plane suggesting non collinear magnetic interactions at the interface. These results may be of interest for the design of oxide interfaces with tailored magnetic structures for new oxide devices

Evaluation of models of sequestration flow in coronary arteries—Physiology versus anatomy?

Background: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as ‘leak’. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. Methods and results: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; −5.2 mL/min, 95% CI −52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI −325 to ＋2549). Conclusion: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data.The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data

Wide antral circumferential vs. ostial pulmonary vein isolation using pulsed field ablation—the butterfly effect

BackgroundWide antral circumferential ablation (WACA) in comparison to ostial pulmonary vein (PV) isolation (PVI) has been attributed with improved rhythm outcome. We investigated the feasibility, lesion formation, and rhythm outcome of WACA-PVI in comparison to ostial-PVI using pulsed field ablation (PFA).MethodsSymptomatic atrial fibrillation (AF) patients (69 years, 67% male; 67% paroxysmal AF) were prospectively enrolled into our single-center registry and underwent first-time ostial-PFA or WACA-PFA, N = 15 each. In all patients, eight pulse trains (2 kV/2.5 s, bipolar, biphasic, 4× basket/flower configuration each) were delivered to each PV. In WACA-PFA, two extra pulse trains in a flower configuration were added to the anterior and posterior antrum of the PVs. For comparison of PFA lesion size, pre- and post-ablation left atrial (LA) voltage maps were acquired using a multipolar spiral catheter together with a three-dimensional electroanatomic mapping system.ResultsWACA-PFA resulted in a significant larger lesion formation than ostial-PFA (45.5 vs. 35.1 cm2, p = 0.001) with bilateral overlapping butterfly shape-like lesions and concomitant posterior LA wall isolation in 73% of patients. This was not associated with increased procedure time, sedation dosage, or exposure to radiation. One-year freedom from AF recurrence was numerically higher after WACA-PFA than ostial-PFA (94% vs. 87%) but not statistically significant (p = 0.68). No organized atrial tachycardias (ATs) were observed. Ostial-PFA patients more often underwent re-ablation due to recurrent AF episodes.ConclusionWACA-PFA is feasible and resulted in significantly wider lesion sets than ostial-PFA. Concomitant posterior LA wall isolation occurred as an epiphenomenon in the majority of patients. The WACA approach was associated with neither increased procedure and fluoroscopy times nor statistically significant differences in 1-year rhythm outcome. ATs were absent

Randomisierter Vergleich systolischer und diastolischer CT-Datensätze zur Planung der kathetergestützten Aortenklappenimplantation: Eine prospektive Outcome Studie

Hintergrund und Ziele Der transkutane, kathetergestützte Aortenklappenersatz ist ein interventionelles Verfahren zur Behandlung einer symptomatischen, hochgradigen Aortenklappenstenose. Der minimalinvasive Eingriff wurde für Patienten konzipiert, die aufgrund ihrer Multimorbidität einem operativen Aortenklappenersatz nicht zugeführt werden konnten. Nichtunterlegenheitsstudien wie die PARTNER- und SURTAVI-Trials haben dazu geführt, dass die Indikationsstellung zunehmend breiter gestellt wird. Nach epidemiologischen Schätzungen ist anzunehmen, dass die Prävalenz der hochgradigen Aortenklappenstenose und somit auch die Rate an interventionellen Eingriffen steigen wird. Prozedurale sowie technische Fortschritte, eine progressive Lernkurve mit zunehmender Expertise in den kardiologischen Zentren haben den transkutan, kathetergestützten Aortenklappenersatz zu einer fortwährend sicheren Intervention gemacht. Relevante Komplikationen können sich in Form einer residuellen paravalvulären Aortenklappeninsuffizienz manifestieren, die langfristig Einfluss auf das Patientenoutcome haben kann. Die Ursachen einer relevanten Aortenklappeninsuffizienz sind multifaktoriell: Neben anatomischen und dynamischen Faktoren können die präprozedurale Diagnostik zur Prothesengrößenbestimmung und die Implantationstechnik zu einer verbleibenden Insuffizienz führen. Mittels der kardialen Computertomographie ist es möglich, mit hoher Auflösung die Anatomie der Aortenwurzel und des Aortenklappenannulus darzustellen. Diese Messmodalität ermöglicht im Vergleich zu anderen bildgebenden Verfahren eine genauere Analyse der annulären Dimensionen. Aktuell wird eine systolische Akquisition zur Prothesengrößenbestimmung vor TAVI empfohlen. Im Rahmen dieser Ausarbeitung sollte in einem klinischen Setting überprüft werden, ob unterschiedliche computertomographische Messmodalitäten einen signifikanten Einfluss auf die Inzidenz einer postinterventionellen paravalvulären Aortenklappeninsuffizienz und auf das Patientenoutcome haben können. Miteinander verglichen wurden in einer prospektiven Analyse Messungen während des systolischen und diastolischen Herzzyklus. Methoden 160 Patienten wurden eingeschlossen. In einem 1:1 Verhältnis erfolgte eine Randomisierung entsprechend zur systolischen oder diastolischen Bestimmung der Dimensionen des Aortenannulus. Zur Datenerhebung nutzten wir ein Dual Source CT System (Somatom Force, Siemens Healthineers, Forchheim, Deutschland) mit einer EKG-synchronisierten Spiralakquisition. Die systolische Datenerfassung erfolgte 300ms nach der R-Zacke. Als diastolische Akquisition wurde der Zeitpunkt 60% zwischen zwei R-R-Zacken definiert. Es wurde eine Schichtdicke von 0.75mm und ein Inkrement von 0.5mm gewählt. Annuläre Kalzifikationen wurden entsprechend einer standardisierten, visuellen Analogskala in vier Schweregrade eingeteilt. Als primärer Endpunkt wurde eine paravalvuläre Aortenklappeninsuffizienz ≥ °II definiert. Sekundäre Endpunkte beinhalteten die Häufigkeit an Nachdilatationen sowie Mortalitätsraten nach 30 und 365 Tagen. Zur statistischen Analyse verwendeten wir die Software SPSS 21.0 (SPSS Inc., Chicago, IL, USA). Die statistische Illustration erfolgte mittels Prism v7.0 (GraphPad Software Inc., La Jolla, CA). Ergebnisse Von 160 Patienten mussten 39 aufgrund von verschiedenen Gründen (Tod, Malignom, Valve-in-Valve, operativer Aortenklappenersatz) aus der weiteren Analyse ausgeschlossen werden. Insgesamt 62 Patienten aus der systolischen Kohorte sowie 59 Patienten aus dem diastolischen Studienarm wurden genauer betrachtet (mittleres Alter 82±5 versus 83±6 Jahre, p>0.5). Baselinecharakteristika und das operative Sterblichkeitsrisiko zeigten keinen signifikanten Unterschied (log. EuroScore 25.9±18.3% versus 26.3±14.0%, p=0.5). Sowohl die annuläre Fläche, der mittlere Diameter als auch der Perimeter zeigten in den computertomographischen Auswertungen keinen signifikanten Unterschied zwischen beiden Gruppen (495±95mm², 25±4mm und 78±16mm in der Systole versus 483±94mm², 25±2mm und 78±16mm in der Diastole, p>0.2). Vergleichsweise ähnlich war auch der Grad an Kalzifikationen des Aortenklappenannulus (Grad 0 zu 53% versus 55%, Grad 1 zu 31% versus 24%, Grad 2 zu 11% versus 10% und Grad 3 zu 5% versus 7%, p>0.4). Die Wahl des Prothesentyps (ballonexpandierbare Prothesen 81% versus 86% und selbstexpandierbare Prothesen 19% versus 14%, p>0.3) und der Prothesengrößen waren nicht signifikant unterschiedlich. Eine paravalvuläre Aortenklappeninsuffizienz ≥ °II nach Sellers manifestierte sich in der Aortographie zu 16% in der Gruppe, die nach systolischer Akquisition einen Aortenklappenersatz erhalten hat, gegenüber 15% entsprechend nach diastolischer Akquisition (p=0.8). Die Rate an Nachdilatationen mittels Ballonkatheter zur Reduktion einer relevanten Leckage unterschied sich ebenfalls nicht signifikant (1 Nachdilatation in 47% versus 54% der Fälle, 2 Nachdilatationen in 2% versus 2% der Fälle, p=0.4). Hinsichtlich der Sterblichkeit nach 30 und 365 Tagen zeigten sich vergleichbare Mortalitätsraten (30-Tages-Mortalität 8% versus 2% (kumulativ: 5%), p=0.1; 1-Jahres-Mortaliät 18% versus 14% (kumulativ: 16%), p=0.5). Schlussfolgerungen Zusammenfassend scheinen die EKG-synchronisierte systolische und diastolische computertomographische Akquisition zur Größenbestimmung der Aortenklappenprothese in diesem prospektiv randomisierten, klinischen Setting entsprechend des prozeduralen Erfolgs und des Outcomes nach 1 Jahr gleichwertig zu sein

Safety and Feasibility of Catheter Ablation Procedures in Patients with Bleeding Disorders

Aims/Objectives: Patients with bleeding disorders are a rare and complex population in catheter ablation (CA) procedures. The most common types of bleeding disorders are von Willebrand disease (VWD) and hemophilia A (HA). Patients with VWD or HA tend to have a higher risk of bleeding complications compared to other patients. There is a lack of data concerning peri- and postinterventional coagulation treatment. We sought to assess the optimal management of patients with VWD and HA referred for catheter ablation procedures. Methods and Results: In this study, we analyzed patients with VWD or HA undergoing CA procedures at two centers in Germany and Switzerland between 2016 and 2021. Clotting factors were administered in conjunction with hemostaseological recommendations. CA was performed as per the institutional standard. During the procedure, unfractionated heparin (UFH) was given intravenously with respect to the activated clotting time (ACT). Primary endpoints included the feasibility of the procedure, bleeding complications, and thromboembolic events during the procedure. Secondary endpoints included bleeding complications and thromboembolic events up to one year after catheter ablation. A total of seven patients (three VWD Type I, one VWD Type IIa, three HA) underwent 10 catheter ablation procedures (pulmonary vein isolation (PVI): two × radiofrequency (RF), one × laser balloon (LB), one × cryoballoon (CB); PVI + cavotricuspid isthmus (CTI): one × RF; PVI + left atrial appendage isolation (LAAI): one × RF; Premature ventricular contraction (PVC): three × RF; Atrioventricular nodal reentrant tachycardia (AVNRT): one × RF). VWD patients received 2000–3000 IE Wilate i.v. 30 to 45 min prior to ablation. Patients with HA received 2000–3000 IE factor VIII before the procedure. All patients undergoing PVI received UFH (cumulative dose 9000–18,000 IE) with a target ACT of >300 s. All patients after PVI were started on oral anticoagulation (OAC) 12 h after ablation. Two patients received aspirin (acetylsalicylic acid; ASA) for 4 weeks after the ablation of left-sided PVCs. No anticoagulation was prescribed after slow pathway modulation in a case with AVNRT. No bleeding complications or thromboembolic events were reported. During a follow-up of one year, one case of gastrointestinal bleeding occurred following OAC withdrawal after LAA occlusion. Conclusions: After the substitution of clotting factors, catheter ablation in patients with VWD and HA seems to be safe and feasible

Safety and Feasibility of Catheter Ablation Procedures in Patients with Bleeding Disorders

AIMS/OBJECTIVES Patients with bleeding disorders are a rare and complex population in catheter ablation (CA) procedures. The most common types of bleeding disorders are von Willebrand disease (VWD) and hemophilia A (HA). Patients with VWD or HA tend to have a higher risk of bleeding complications compared to other patients. There is a lack of data concerning peri- and postinterventional coagulation treatment. We sought to assess the optimal management of patients with VWD and HA referred for catheter ablation procedures. METHODS AND RESULTS In this study, we analyzed patients with VWD or HA undergoing CA procedures at two centers in Germany and Switzerland between 2016 and 2021. Clotting factors were administered in conjunction with hemostaseological recommendations. CA was performed as per the institutional standard. During the procedure, unfractionated heparin (UFH) was given intravenously with respect to the activated clotting time (ACT). Primary endpoints included the feasibility of the procedure, bleeding complications, and thromboembolic events during the procedure. Secondary endpoints included bleeding complications and thromboembolic events up to one year after catheter ablation. A total of seven patients (three VWD Type I, one VWD Type IIa, three HA) underwent 10 catheter ablation procedures (pulmonary vein isolation (PVI): two × radiofrequency (RF), one × laser balloon (LB), one × cryoballoon (CB); PVI + cavotricuspid isthmus (CTI): one × RF; PVI + left atrial appendage isolation (LAAI): one × RF; Premature ventricular contraction (PVC): three × RF; Atrioventricular nodal reentrant tachycardia (AVNRT): one × RF). VWD patients received 2000-3000 IE Wilate i.v. 30 to 45 min prior to ablation. Patients with HA received 2000-3000 IE factor VIII before the procedure. All patients undergoing PVI received UFH (cumulative dose 9000-18,000 IE) with a target ACT of &gt;300 s. All patients after PVI were started on oral anticoagulation (OAC) 12 h after ablation. Two patients received aspirin (acetylsalicylic acid; ASA) for 4 weeks after the ablation of left-sided PVCs. No anticoagulation was prescribed after slow pathway modulation in a case with AVNRT. No bleeding complications or thromboembolic events were reported. During a follow-up of one year, one case of gastrointestinal bleeding occurred following OAC withdrawal after LAA occlusion. CONCLUSIONS After the substitution of clotting factors, catheter ablation in patients with VWD and HA seems to be safe and feasible

Metacognitive theory and assessment in dementia: Do we recognize our areas of weakness?

Anosognosia, disordered awareness of cognitive and behavioral deficits, is a striking and common symptom of Alzheimer's disease (AD), yet its etiology, clinical correlates, and prognostic value are unclear. Historically, disordered awareness has been a conceptually challenging phenomenon, evidenced by the numerous and diverse theories that aim to explain the manner in which this syndrome arises. We review many of these theories, focusing on the neuroanatomic substrates of awareness, and highlighting the potential roles of critical regions such as the right prefrontal and parietal cortices in enabling self-awareness. We then address methodological limitations such as use of subjective measurement tools that likely contribute to the conceptual ambiguity surrounding anosognosia. We argue that metacognitive techniques used in healthy adults, such as the Feeling of Knowing task, offer models for dissecting awareness into clear and identifiable cognitive components in patients with AD. We critique several studies that have pioneered such tasks in AD, and offer guidelines for future implementation of such methods. A final goal of this review is to advocate for a multidimensional approach to studying metacognitive skills that will facilitate the objective investigation of deficit awareness as it relates to a variety of disease variables such as prognosis, neuropsychological profile, neuropathological distribution, psychiatric symptoms, and clinical course