Publications by authors named "John D Day"

111 Publications

Dr. Louise Eisenhardt's personal notes: how she and Dr. Cushing collected data and followed patients.

J Neurosurg 2021 Sep 24:1-6. Epub 2021 Sep 24.

1Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Dr. Louise Eisenhardt was one of the first neuropathologists and was responsible for the development of tumor diagnosis guidelines. This historical vignette reviews her previously unseen handwritten notes in which she describes methods used by her and Dr. Harvey Cushing to obtain patient follow-up data for their Brain Tumor Registry. Her description spans 50 years, using "every possible clue to be jumped upon in [their] clinical records and correspondence." Their follow-up was divided into two periods: early follow-up (1912-1932) and registry (1933-1961). During early follow-up, patients were asked to write to them on the anniversary of their operation. The foundation of the registry necessitated the use of "considerable effort on [their] part to gather up old threads" including renewed contact with patients after 15-20 years. Methods of follow-up included continued verbal and written correspondence with patients and "strong-arm methods," including use of the Fuller Brush man and the exhumation of a body. Drs. Eisenhardt and Cushing believed "every case was important in adding to our collective knowledge of various types of tumors particularly in relationship to life expectancies and suggesting improvement in surgical treatments." Dr. Eisenhardt's meticulous record keeping allows for insights into the first known outcomes-related tumor registry in neurosurgery.
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http://dx.doi.org/10.3171/2021.4.JNS201086DOI Listing
September 2021

Long-term Outcomes in Patients Treated with Flecainide for Atrial Fibrillation with Stable Coronary Artery Disease.

Am Heart J 2021 Sep 16. Epub 2021 Sep 16.

Department of Medicine, School of Medicine, University of Utah, Salt Lake City, Utah. Electronic address:

Background: Class 1C antiarrhythmic drugs(AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction(MI). Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease(CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation(AF) in patients with CAD without a prior MI.

Methods: In 24,315 patients treated with the initiation of AADs, two populations were evaluated: 1. propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n=1,114, versus class-3 AAD, n=1,114); 2. AF patients who had undergone a PCI or CABG (flecainide, n=150, and class-3 AAD, n=1,453). Outcomes at three years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups.

Results: At 3 years, mortality (9.1% vs 19.3%, p<0.0001), HF hospitalization (12.5% vs 18.3%, p<0.0001), MACE (22.9% vs 36.6%, p<0.0001), and VT (5.8% vs 8.5%, p=0.02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs25.8%, p=0.26), HF hospitalization (24.5% vs 26.1%, p=0.73), VT (10.9% vs 14.7%, p=0.28) and MACE (44.5% vs 49.5%, p=0.32).

Conclusions: Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.
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http://dx.doi.org/10.1016/j.ahj.2021.08.013DOI Listing
September 2021

Maturation of the anterior petrous apex: surgical relevance for performance of the middle fossa transpetrosal approach in pediatric patients.

J Neurosurg 2021 Sep 17:1-7. Epub 2021 Sep 17.

2Department of Neurosciences and Pediatrics, University of California, San Diego, San Diego.

Objective: The middle fossa transpetrosal approach to the petroclival and posterior cavernous sinus regions includes removal of the anterior petrous apex (APA), an area well studied in adults but not in children. To this end, the authors performed a morphometric analysis of the APA region during pediatric maturation.

Methods: Measurements of the distance from the clivus to the internal auditory canal (IAC; C-IAC), the distance of the petrous segment of the internal carotid artery (petrous carotid; PC) to the mesial petrous bone (MPB; PC-MPB), the distance of the PC to the mesial petrous apex (MPA; PC-MPA), and the IAC depth from the middle fossa floor (IAC-D) were made on thin-cut CT scans from 60 patients (distributed across ages 0-3, 4-7, 8-11, 12-15, 16-18, and > 18 years). The APA volume was calculated as a cylinder using C-IAC (length) and PC-MPB (diameter). APA pneumatization was noted. Data were analyzed by laterality, sex, and age.

Results: APA parameters did not differ by laterality or sex. APA pneumatization was seen on 20 of 60 scans (33.3%) in patients ≥ 4 years. The majority of the APA region growth occurred by ages 8-11 years, with PC-MPA and PC-MPB increasing 15.9% (from 9.4 to 10.9 mm, p = 0.08) and 23.5% (from 8.9 to 11.0 mm, p < 0.01) between ages 0-3 and 8-11 years, and C-IAC increasing 20.7% (from 13.0 to 15.7 mm, p < 0.01) between ages 0-3 and 4-7 years. APA volume increased 79.6% from ages 0-3 to 8-11 years (from 834.3 to 1499.2 mm3, p < 0.01). None of these parameters displayed further significant growth. Finally, IAC-D increased 51.1% (from 4.3 to 6.5 mm, p < 0.01) between ages 0-3 and adult, without significant differences between successive age groups.

Conclusions: APA development is largely complete by the ages of 8-11 years. Knowledge of APA growth patterns may aid approach selection and APA removal in pediatric patients.
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http://dx.doi.org/10.3171/2021.3.JNS202648DOI Listing
September 2021

Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon.

Front Oncol 2021 26;11:662260. Epub 2021 Apr 26.

Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.
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http://dx.doi.org/10.3389/fonc.2021.662260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108694PMC
April 2021

Surgical Relevance of Pediatric Anterior Clinoid Process Maturation for Anterior Skull Base Approaches.

Oper Neurosurg (Hagerstown) 2021 02;20(3):E200-E207

Department of Neurosciences and Pediatrics, University of California, San Diego, San Diego, California.

Background: Removal of the anterior clinoid process (ACP) can expand anterior skull base surgical corridors. ACP development and anatomical variations are poorly defined in children.

Objective: To perform a morphometric analysis of the ACP during pediatric maturation.

Methods: Measurements of ACP base thickness (ACP-BT), midpoint thickness (ACP-MT), length (ACP-L), length from optic strut to ACP tip (ACP-OS), pneumatization (ACP-pneumo), and the presence of an ossified carotico-clinoid ligament (OCCL) or interclinoid ligament (OIL) were made from high-resolution computed-tomography scans from 60 patients (ages 0-3, 4-7, 8-11 12-15, 16-18, and >18 yr). Data were analyzed by laterality, sex, and age groups using t-tests and linear regression.

Results: There were no significant differences in ACP parameters by laterality or sex, and no significant growth in ACP-BT or ACP-MT during development. From ages 0-3 yr to adult, mean ACP-L increased 49%, from 7.7 to 11.5 mm. The majority of ACP-L growth occurred in 2 phases between ages 0-3 to 8-11 and ages 16-18 to adult. Conversely, ACP-OS was stable from ages 0-3 to 8-11 but increased by 63% between ages 8-11 to adult. Variations in ACP morphology (OCCL/OIL/ACP-pneumo) were found in 15% (9/60) of scans. OCCL and OIL occurred in patients as young as 3 yrs, whereas ACP-pneumo was not seen in patients younger than 11 yrs.

Conclusion: The ACP demonstrates stable thickness and a complex triphasic elongation and remodeling pattern with development, the understanding of which may facilitate removal in patients <12. Clinically relevant ACP anatomic variations can occur at any age.
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http://dx.doi.org/10.1093/ons/opaa374DOI Listing
February 2021

Neurosurgical management of perineural metastases: A case series and review of the literature.

Surg Neurol Int 2020 25;11:206. Epub 2020 Jul 25.

Department of Neurological Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Background: Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and underreported, phenomenon. Adding complexity to reaching a diagnosis and treating perineural spread (PNS) is the finding that patients may have no known primary tumor, history of skin cancer, and/or incidental PNI in the primary tumor. These delays in diagnosis and treatment are further compounded by an already slow disease process and often require multidisciplinary care with combinations of stereotactic radiosurgery, surgical resection, and novel treatments such as checkpoint inhibitors.

Methods: Six patients with metastatic cancer to the cranial nerves who underwent Gamma Knife radiosurgery (GKRS) treatment were chosen for retrospective analysis. This information included age, gender, any past surgeries (both stereotactic and regular surgery), dose of radiation and volume of the tumor treated in the GKRS, date of PNS, comorbidities, the patient follow-up, and pre- and post-GKRS imaging. The goal of the follow-up with radiographing imaging was to assess the efficacy of GKSS.

Results: The clinical course of six patients with PNS is presented. Patients followed variable courses with mixed outcomes: two patients remain living, one was lost to follow-up, and three expired with a median survival of 12 months from date of diagnosis. Patients at our institution are ideally followed for life.

Conclusion: Given the morbidity and mortality of PNS of cancer, time is limited, and further understanding is required to improve outcomes. Here, we provide a case series of patients with PNS treated with stereotactic radiosurgery, discuss their clinical courses, and review the known literature.
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http://dx.doi.org/10.25259/SNI_146_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451152PMC
July 2020

Rates and Anticoagulation Treatment of Known Atrial Fibrillation in Patients with Acute Ischemic Stroke: A Real-World Study.

Adv Ther 2020 10 27;37(10):4370-4380. Epub 2020 Aug 27.

Atrial Fibrillation Centre and Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Introduction: Known atrial fibrillation (AF) rate and appropriate prescription of oral anticoagulants (OACs) in acute ischemic stroke (AIS) patients with AF in China are not as well known as in Western countries.

Methods: Known AF and unknown AF, rate and adequacy of OACs use of AIS patients with AF attending five hospitals from April 2018 to August 2019 in the northwest region of China were investigated.

Results: A total of 344 patients were enrolled. Of these, 237 (AF-known group; 237/344, 68.9%) and 107 patients (AF-unknown group; 107/344, 31.1%) were diagnosed with AF before and after AIS during this hospitalization, respectively. In the AF-known group with echocardiography results (178 patients, including 103 female and 75 male patients), 154 of overall, 88 of female and 66 of male patients, respectively, were indicated to be taking OACs. However, the actual OACs proportion was much lower [overall (30.5%, 47/154); female (31.8%, 28/88) and male (28.8%, 19/66) patients] than indicated. Only one female patient met the guideline-based criteria for OACs. As for patients diagnosed with massive cerebral infraction (MCI; 43.0%, 148/344), the known AF rate was 65.5% (97/148). Among the MCI patients in the AF-known group with echocardiography results (61 patients), 50 patients had an OACs indication. However, only 22.0% (11/50) of these patients took OACs, and none met the guideline-based criteria for OACs.

Conclusions: This study revealed a low known AF rate, low OACs use rate and low rate of meeting the guideline-based criteria for OACs in AIS patients with AF in the northwest region of China. These findings indicated the importance of AF as a public health problem in China.
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http://dx.doi.org/10.1007/s12325-020-01469-wDOI Listing
October 2020

Cardiovascular disease during the COVID-19 pandemic: Think ahead, protect hearts, reduce mortality.

Cardiol J 2020 13;27(5):616-624. Epub 2020 Aug 13.

Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Coronavirus disease 2019 (COVID-19) is rapidly spreading globally. As of October 3, 2020, the number of confirmed cases has been nearly 34 million with more than 1 million fatalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for COVID-19. Newly diagnosed and worsening cardiovascular disease are common complications in COVID-19 patients, including acute cardiac injury, hypertension, arrhythmia, myocardial infarction, heart failure and sudden cardiac arrest. The mechanisms contributing to cardiac disease burden include hypoxemia, inflammatory factor storm, dysfunctional angiotensin converting enzyme 2 (ACE2), and drug-induced cardiac toxicity. Notably, the macrophages expressing ACE2 as direct host cells of SARS-CoV-2 secrete chemokine and inflammatory cytokines, as well as a decrease in cellular immune responses to SARS-CoV-2 infection due to elevated exhaustion levels and dysfunctional diversity of T cells, that may be accountable for the "hyperinflammation and cytokine storm syndrome" and subsequently acute cardiac injury and deteriorating cardiovascular disease in COVID-19 patients. However, no targeted medication or vaccines for COVID-19 are yet available. The management of cardiovascular disease in patients with COVID-19 include general supportive treatment, circulatory support, other symptomatic treatment, psychological assistance as well as online consultation. Further work should be concentrated on better understanding the pathogenesis of COVID-19 and accelerating the development of drugs and vaccines to reduce the cardiac disease burden and promote the management of COVID-19 patients, especially those with a severe disease course and cardiovascular complications.
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http://dx.doi.org/10.5603/CJ.a2020.0101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078991PMC
November 2020

Procedural Patterns and Safety of Atrial Fibrillation Ablation: Findings From Get With The Guidelines-Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2020 09 23;13(9):e007944. Epub 2020 Jul 23.

Duke Clinical Research Institute (Z.L., D.N.H., R.A.M., J.P.P.), Duke University Medical Center.

Background: Catheter ablation is an increasingly used treatment for symptomatic atrial fibrillation (AF). However, there are limited prospective, nationwide data on patient selection and procedural characteristics. This study describes patient characteristics, techniques, treatment patterns, and safety outcomes of patients undergoing AF ablation.

Methods: A total of 3139 patients undergoing AF ablation between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation registry from 24 US centers were included. Patient demographics, medical history, procedural details, and complications were abstracted. Differences between paroxysmal and patients with persistent AF were compared using Pearson χ and Wilcoxon rank-sum tests.

Results: Patients undergoing AF ablation were predominantly male (63.9%) and White (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and patients with persistent AF had more comorbidities than patients with paroxysmal AF. Drug refractory, paroxysmal AF was the most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radiofrequency ablation with contact force sensing was the most common ablation modality (70.5%); 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations; the most common adjunctive lesions included left atrial roof or posterior/inferior lines, and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases.

Conclusions: More than 98% of AF ablations among participating sites are performed for class I or class IIA indications. Contact force-guided radiofrequency ablation is the dominant technique and pulmonary vein isolation the principal lesion set. In-hospital complications are uncommon and rarely life-threatening.
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http://dx.doi.org/10.1161/CIRCEP.119.007944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502261PMC
September 2020

A novel Cas9-targeted long-read assay for simultaneous detection of IDH1/2 mutations and clinically relevant MGMT methylation in fresh biopsies of diffuse glioma.

Acta Neuropathol Commun 2020 06 20;8(1):87. Epub 2020 Jun 20.

Department of Neurosurgery, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.

Molecular biomarkers provide both diagnostic and prognostic results for patients with diffuse glioma, the most common primary brain tumor in adults. Here, we used a long-read nanopore-based sequencing technique to simultaneously assess IDH mutation status and MGMT methylation level in 4 human cell lines and 8 fresh human brain tumor biopsies. Currently, these biomarkers are assayed separately, and results can take days to weeks. We demonstrated the use of nanopore Cas9-targeted sequencing (nCATS) to identify IDH1 and IDH2 mutations within 36 h and compared this approach against currently used clinical methods. nCATS was also able to simultaneously provide high-resolution evaluation of MGMT methylation levels not only at the promoter region, as with currently used methods, but also at CpGs across the proximal promoter region, the entirety of exon 1, and a portion of intron 1. We compared the methylation levels of all CpGs to MGMT expression in all cell lines and tumors and observed a positive correlation between intron 1 methylation and MGMT expression. Finally, we identified single nucleotide variants in 3 target loci. This pilot study demonstrates the feasibility of using nCATS as a clinical tool for cancer precision medicine.
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http://dx.doi.org/10.1186/s40478-020-00963-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305623PMC
June 2020

Surgical Treatment of Symptomatic Small Medial Petrous Meningiomas Causing Trigeminal Neuralgia.

World Neurosurg 2020 07 29;139:e761-e768. Epub 2020 Apr 29.

Department of Neurosurgery, University of Arkansas Medical Sciences, Little Rock, Arkansas, USA. Electronic address:

Background: Symptomatic trigeminal neuralgia caused by small (<3 cm) skull base meningiomas is treated by radiosurgery or surgical resection. Although radiosurgery is less invasive, surgical resection provides more rapid resolution of symptoms. We reviewed a short series of patients who underwent an anterior transpetrosal approach for surgical resection of meningiomas causing trigeminal neuralgia.

Methods: A retrospective review of 5 consecutive patients with meningiomas causing trigeminal neuralgia of the senior author was included. Preoperative parameters (size, proximity to critical neurovascular structures, presence of brainstem compression), intraoperative parameters (Simpson grade of resection, loss of brainstem evoked potentials, surgical approach), and outcomes (symptom resolution, extent of resection, follow-up) were recorded.

Results: Patient median age was 67 years (range, 60-73 years). All patients had symptoms concerning trigeminal neuralgia with 2 having associated areas of facial numbness. The anterior transpetrosal approach was used to achieve complete resection (Simpson grade I). Postresection, the trigeminal nerve and brainstem were clearly visible to evaluate neurovascular structures and ensure decompression. No postoperative complications were reported, and all patients experienced sustained symptomatic relief 1 month postsurgery.

Conclusions: With the advent of radiosurgery for skull base meningiomas, surgical resection is not always considered; however, such meningiomas causing trigeminal neuralgia can be resected safely using the anterior transpetrosal approach allowing rapid resolution of symptoms. This review of operative nuances provides a guide for neurosurgeons to provide safe surgical resection.
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http://dx.doi.org/10.1016/j.wneu.2020.04.127DOI Listing
July 2020

Decompression of Cavernous Sinus for Trigeminal Neuropathic Pain From Perineural Spread of Tumor: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2020 Sep;19(3):E304-E305

Department of Neurosurgery, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas.

Head and neck malignancies with perineural spread are rare. Patients can present with neuropathic pain and cranial nerve palsies.1 Skull base approaches for surgical decompression are a consideration for patients to provide symptom relief.2 We demonstrate a frontotemporal extradural approach for a patient with worsening visual symptoms and refractory neuropathic pain in the V1, V2, and V3 distributions and briefly review the relevant anatomy.3-7  A 41-yr-old female with a poorly differentiated carcinoma of the head and neck with an infiltration of the cavernous sinus and perineural spread along the trigeminal nerve presented with severe neuropathic facial pain and anesthesia. She had previously undergone radiosurgery. Magnetic resonance imaging (MRI) demonstrated an interval increase in perineural disease within the cavernous sinus with extension intradurally. Her pain was medically refractory. A 2-dimensional intraoperative video illustrates the microsurgical decompression of her perineural invasion along the skull base as a palliative procedure. The patient recovered well postoperatively and had a symptomatic improvement in her pain and visual symptoms. Her preoperative facial numbness persisted postoperatively as expected. Postoperative imaging demonstrates a gross total resection of the intradural component of the tumor with decompression and expected expansion of the cavernous sinus. Because of the retrospective nature of this report, informed consent was not required. Images within the video have been reproduced from Fukuda et al4 with permission from © Georg Thieme Verlag KG; and Matsuo et al5 by permission of the Congress of Neurological Surgeons.
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http://dx.doi.org/10.1093/ons/opaa033DOI Listing
September 2020

Histology of the vertebral artery-dural junction: relevance to posterolateral approaches to the skull base.

J Neurosurg 2019 Nov 22:1-6. Epub 2019 Nov 22.

5Neurosciences and Pediatrics, University of California-San Diego, La Jolla, California.

Objective: The far-lateral and extreme-lateral infrajugular transcondylar-transtubercular exposure (ELITE) and extreme-lateral transcondylar transodontoid (ELTO) approaches provide access to lesions of the foramen magnum, inferolateral to mid-clivus, and ventral pons and medulla. A subset of pathologies in this region require manipulation of the vertebral artery (VA)-dural interface. Although a cuff of dura is commonly left on the VA to avoid vessel injury during these approaches, there are varying descriptions of the degree of VA-dural separation that is safely achievable. In this paper the authors provide a detailed histological analysis of the VA-dural junction to guide microsurgical technique for posterolateral skull base approaches.

Methods: An ELITE approach was performed on 6 preserved adult cadaveric specimens. The VA-dural entry site was resected, processed for histological analysis, and qualitatively assessed by a neuropathologist.

Results: Histological analysis demonstrated a clear delineation between the intima and media of the VA in all specimens. No clear plane was identified between the connective tissue of the dura and the connective tissue of the VA adventitia.

Conclusions: The VA forms a contiguous plane with the connective tissue of the dura at its dural entry site. When performing posterolateral skull base approaches requiring manipulation of the VA-dural interface, maintenance of a dural cuff on the VA is critical to minimize the risk of vascular injury.
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http://dx.doi.org/10.3171/2019.9.JNS191394DOI Listing
November 2019

Long-term outcomes after low power, slower movement versus high power, faster movement irrigated-tip catheter ablation for atrial fibrillation.

Heart Rhythm 2020 02 6;17(2):184-189. Epub 2019 Aug 6.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, Salt Lake City, Utah.

Background: High power, shorter duration (HPSD) ablation strategies have been advocated to increase efficacy and minimize posterior wall deep tissue thermal injury during atrial fibrillation (AF) ablation.

Objective: The purpose of this study was to determine the long-term outcomes of arrhythmia-free survival from AF and atrial flutter (AFL) between HPSD and low power, longer duration (LPLD) ablation strategies.

Methods: Of a total of 1333 first time AF ablation procedures with 3 years of follow-up, propensity-matched populations for baseline risk factors were created, comprising 402 patients treated with LPLD ablation (30 W for 5 seconds: posterior wall; 30 W for 10-20 seconds: anterior wall) and 402 patients treated with HPSD ablation (50 W for 2-3 seconds: posterior wall; 50 W for 5-15 seconds: anterior wall). AF/AFL outcomes after a 90-day blanking period were assessed.

Results: HPSD ablation was associated with shorter procedure and fluoroscopy times (P < .0001 for both). The recurrence of AF at 1 year (12.9% vs 16.2%; P = .19) and 3 years (26.5% vs 30.7%; P = .23) was similar between LPLD and HPSD groups. AFL was higher at 1 year (7.2% vs 11.2%; P = .03) and 3 years (16.1% vs 21.8%; P = .06; P = .04 after multivariate adjustment) with HPSD ablation. Patients who underwent an LPLD approach had lower rates of need for repeat ablation (21% vs 30%; P = .002).

Conclusion: Long-term freedom from AF rates were not significantly different between both approaches. An HPSD ablation strategy compared with an LPLD approach was associated with an increased risk of AFL and need for repeat ablation but with lowered procedure times.
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http://dx.doi.org/10.1016/j.hrthm.2019.08.001DOI Listing
February 2020

The Impact of Repeated Cardioversions for Atrial Fibrillation on Stroke, Hospitalizations, and Catheter Ablation Outcomes.

J Atr Fibrillation 2019 Apr 30;11(6):2164. Epub 2019 Apr 30.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah.

Background: Long-term outcomes after direct current cardioversion (DCCV) in patients that receive anticoagulation have demonstrated to have no adverse sequela. Less is known about the impact on atrial fibrillation (AF) outcomes and resource utilization of repeated DCCVs that are often required for long-term rhythm control.

Methods: A total of 4,135 AF patients >18 years of age that underwent DCCV with long-term system follow-up were evaluated. Patients were stratified by the number of DCCVs received: 1 (n=2,201), 2-4 (n=1,748), and ≥5 (n=186). Multivariable Cox hazard regression was used to determine the association of DCCV categories to the outcomes of death, AF hospitalization, AF ablation, DCCVs, and stroke/transient ischemic attack.

Results: The average follow-up of the patient population was 1,633.1±1,232.9 (median: 1,438.0) days. Patients who underwent 2-4 and ≥5 DCCVs had more comorbidities, namely hypertension, hyperlipidemia and heart failure. Anticoagulation use was common at the time of DCCV in all groups (89.1%, 91.2%, 91.9%, p=0.06) and amiodarone use increased with increasing DCCV category (30.1%, 43.4%, 52.2, p<0.0001). At 5 years, patients that received more DCCVs had higher rates of repeat DCCVs, AF hospitalizations, and ablations. Stroke rates were not increased. Though not statistically significant, 5-year death was increased when comparing DCCV >5 vs. 1, (HR=1.32 [0.89-1.94], p=0.17).

Conclusions: This study found that the increasing number of DCCVs, despite escalation of other pharmacologic and nonpharmacologic therapies, is a long-term independent risk factor for repeat DCCVs, ablations, and AF hospitalizations among AF patients.
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http://dx.doi.org/10.4022/jafib.2164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652789PMC
April 2019

Stroke and dementia risk in patients with and without atrial fibrillation and carotid arterial disease.

Heart Rhythm 2020 01 9;17(1):20-26. Epub 2019 Jul 9.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah.

Background: Patients with carotid arterial disease (CD) with and without atrial fibrillation (AF) are at risk of stroke. Patients with AF are at a higher risk of stroke and dementia.

Objectives: We sought to understand the risks of stroke, transient ischemic attack (TIA), and dementia in patients with and without AF and CD or a combination of both as well as to determine whether therapies for each disease may influence risks.

Methods: A total of 11,572 patients were included in 4 groups, with 2893 patients populating each group (1: no AF or CD; 2: AF, no CD; 3: CD and no AF; 4: AF and CD) and matched for age, sex, and comorbidities. Long-term outcomes of stroke/TIA and dementia were assessed. Subset analyses of these outcomes were performed in patients with CD treated with revascularization and in patients with AF treated with ablation.

Results: CD increased the risk of stroke/TIA (hazard ratio [HR] 2.74; P < .0001) and dementia (HR 1.44; P < .0001). Similarly, AF increased the risk of stroke/TIA (HR 2.08; P < .0001) and dementia (HR 1.30; P = .004). The coexistence of AF and CD further augmented the risk of both end points. CD revascularization was associated with a decreased risk of dementia (HR 0.47; P < .0001) but not stroke. Ablation of AF improved outcomes of stroke/TIA (HR 0.55; P = .002), particularly in those with CD (HR 0.36; P < .0001), and was associated with a reduced risk of dementia (HR 0.51; P = .04).

Conclusion: CD and AF augment risk of stroke/TIA and dementia in the general population, and the coexistence of both diseases is additive in risk. Ablation of AF was associated with lower risk, the magnitude of which was greater in those with CD.
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http://dx.doi.org/10.1016/j.hrthm.2019.07.007DOI Listing
January 2020

Rationale and design of the impact of anticoagulation therapy on the Cognitive Decline and Dementia in Patients with Nonvalvular Atrial Fibrillation (CAF) Trial: A Vanguard study.

Clin Cardiol 2019 May 10;42(5):506-512. Epub 2019 Apr 10.

Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.

Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Observational trials suggest that the implementation and quality of long-term anticoagulation impact dementia risk. Emerging evidence suggests that direct oral anticoagulants may improve long-term risk of dementia in AF patients. This manuscript describes the rational and trial design of the the Cognitive Decline and Dementia in Atrial Fibrillation Patients (CAF) Trial. CAF investigates if AF patients randomized to dabigatran etexilate will have long-term higher cognition scores and lower rates of dementia compared in the long term to dose-adjusted warfarin (International Normalized Ratio [INR]: 2.0-3.0). As of 27 February 2019, a total of 120 subjects will be enrolled at one investigational site in the United States and will be followed for 2 years after study enrollment. To date, 97 have been enrolled. The average age is 74.2 years, 53% are male, and 9% had a prior stroke. In this Vanguard study, patients will be followed for 2 years after study enrollment. These prospective, randomized data will inform the understanding of two anticoagulants in AF patients as it relates to risk of cognitive decline and dementia. Cranial imaging and biomarkers collected will assist in understanding mechanisms of brain injury.
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http://dx.doi.org/10.1002/clc.23181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522997PMC
May 2019

Mechanisms of Improved Mortality Following Ablation: Does Ablation Restore Beta-Blocker Benefit in Atrial Fibrillation/Heart Failure?

Cardiol Clin 2019 May 27;37(2):177-183. Epub 2019 Feb 27.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, 5169 Cottonwood St, Murray, UT 84017, USA.

Observational trials have shown that atrial fibrillation ablation favorably impacts long-term outcomes in systolic heart failure. These outcomes have been confirmed by randomized prospective trials highlighting the favorable impact of ablation on left ventricular function and remodeling, risk of heart failure hospitalization, and mortality. Ablation along with established heart failure medications is new and supported conceptually by the value of restoring sinus rhythm, avoiding long-term antiarrhythmic drugs, and minimizing drug-drug interactions. Observational data suggest a potential long-term benefit of beta-blockers with ablation that becomes augmented as follow-up is extended from 1 to 5 years.
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http://dx.doi.org/10.1016/j.ccl.2019.01.011DOI Listing
May 2019

Low complication rates using high power (45-50 W) for short duration for atrial fibrillation ablations.

Heart Rhythm 2019 02;16(2):165-169

Intermountain Medical Center Heart Institute, Salt Lake City, Utah.

Background: Many centers use radiofrequency (RF) energy at 25-35 W for 30-60 seconds. There is a safety concern about using higher power, especially on the posterior wall.

Objective: The purpose of this study was to examine complication rates for atrial fibrillation (AF) ablations performed with high-power, short-duration RF energy.

Methods: We examined the complication rates of 4 experienced centers performing AF ablations at RF powers from 45-50 W for 2-15 seconds per lesion. In total, 13,974 ablations were performed in 10,284 patients. On the posterior wall, 11,436 ablations used 45-50 W for 2-10 seconds, and 2538 ablations used power reduced to 35 W for 20 seconds. Esophageal temperature monitoring was used in 13,858 (99.2%).

Results: Demographics were age 64 ± 11 years, male 68%, left atrial size 4.4 ± 0.7 cm, paroxysmal AF 37%, persistent AF 42%, longstanding AF 20%, antiarrhythmic drugs failed 1.4 ± 0.7, hypertension 54%, diabetes 15%, previous cerebrovascular accident/transient ischemic attack 7%, and CHADS-VASc score 2.1 ± 1.4. Procedural time was 116 ± 41 minutes. Complications were death in 2 (0.014%; 1 due to stroke and 1 due to atrioesophageal fistula), pericardial tamponade in 33 (0.24%; 26 tapped, 7 surgical), strokes <48 hours in 6 (0.043%), strokes 48 hours-30 days in 6 (0.043%), pulmonary vein stenosis requiring intervention in 2 (0.014%), phrenic nerve paralysis in 2 (0.014%; both resolved), steam pops 2 (0.014%) without complications, and catheter char 0 (0.00%). There was 1 atrioesophageal fistula in 11,436 ablations using power 45-50 W on the posterior wall and 3 in 2538 ablated with 35 W on the posterior wall (P = .021), although 2 of the 3 had no esophageal monitoring during a fluoroless procedure.

Conclusion: AF ablations can be performed at 45-50 W for short durations with very low complication rates. High-power, short-duration ablations have the potential to shorten procedural and total RF times and create more localized and durable lesions.
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http://dx.doi.org/10.1016/j.hrthm.2018.11.031DOI Listing
February 2019

The Impact of Gender on Atrial Fibrillation Incidence and Progression to Dementia.

Am J Cardiol 2018 11 3;122(9):1489-1495. Epub 2018 Aug 3.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah; Stanford University, Department of Internal Medicine, Palo Alto, California. Electronic address:

There are a paucity of data regarding the role of gender and atrial fibrillation (AF) on cognitive decline and incidence of dementia. Such data may provide insight into the disproportionate incidence of dementia in women and may help identify high-risk characteristics to target for prevention. We examined patients who underwent coronary angiography at an Intermountain Healthcare Medical Center and enrolled in a prospective cardiovascular database. To be included, patients could not have a previous diagnosis of AF or dementia and had to have 5years of follow-up. Endpoints included incident AF and dementia. Study cohort consisted of 35,608 patients without a previous history of AF or dementia, with 14,377 (40.4%) being woman. Women had lower rates of hypertension, diabetes, coronary artery disease, and prior myocardial infarction, but higher rates of prior stroke. Men had a higher incidence of 5-year and long-term AF. However, women trended toward a higher incidence of 5-year and long-term dementia and stroke compared with men. In all groups of patients with and without AF, prior stroke predicted cognitive decline. In patients without a history of or development of AF, diabetes significantly increased risk of dementia. Women have higher rates of dementia over time than men, driven by higher baseline stroke rates and nontraditional cardiovascular risk factors. The higher dementia rates were in the setting of lower AF rates. However, in both men and women who develop AF, dementia rates are increased and do not show gender-based differences in risk.
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http://dx.doi.org/10.1016/j.amjcard.2018.07.031DOI Listing
November 2018

Vagus nerve injury symptoms after catheter ablation for atrial fibrillation.

Pacing Clin Electrophysiol 2018 04 30;41(4):389-395. Epub 2018 Mar 30.

Intermountain Medical Center Heart Institute, Murray, UT, USA.

Background: Vagus nerve injury during catheter ablation for atrial fibrillation can significantly impact quality of life and result in lingering gastrointestinal symptoms. This study was designed to define risk factors of vagus nerve injury, symptoms, prevalence, and temporal resolution.

Methods: A total of 100 patients undergoing radiofrequency catheter ablation (RFCA) were enrolled and consented to participate in the study. Patients completed a 22-item questionnaire that included questions specific to vagus nerve injury symptomatology during their baseline visit and at 1 and 3 months post-RFCA.

Results: The average age of the population was 63 ± 10.6 years and 68% were male. A total of 100 patients completed their baseline questionnaire (90 patients completed the 1-month questionnaires and 85 patients completed the 3-month questionnaires). Symptoms rated as moderate were prevalent at baseline (trouble swallowing 13%, bloating 26%, feeling full 20%), and increased in all categories analyzed at 1 month and with the exception of trouble swallowing returned to the preablation percentages at 3 months (heartburn 22.4%, trouble swallowing 18.8%, bloating 16.5%, nausea 8.2%, vomiting 3.5%, constipation 18.8%, diarrhea 16.4%, feeling full 15.3%). Severe rated symptoms of trouble swallowing (2-5.5%), bloating (5-7.6%), and early satiety (5-9.8%) increased at 1 month and bloating and early satiety percentages remained approximately two times higher at 3 months (trouble swallowing 2.4%, bloating 8.2%, early satiety 7.1%).

Conclusion: The majority of symptoms were resolved by 3 months, although those patients who rate bloating and early satiety at a severe rating may have persistent symptoms.
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http://dx.doi.org/10.1111/pace.13304DOI Listing
April 2018

Extended middle fossa approach to lateralized pontine cavernomas in children.

J Neurosurg Pediatr 2018 04 2;21(4):384-388. Epub 2018 Feb 2.

1Department of Pediatric Neurosurgery, University of California, San Diego, California.

OBJECTIVE Treatment of hemorrhagic cavernous malformations within the lateral pontine region demands meticulous surgical planning and execution to maximize resection while minimizing morbidity. The authors report a single institution's experience using the extended middle fossa rhomboid approach for the safe resection of hemorrhagic cavernomas involving the lateral pons. METHODS A retrospective chart review was performed to identify and review the surgical outcomes of patients who underwent an extended middle fossa rhomboid approach for the resection of hemorrhagic cavernomas involving the lateral pons during a 10-year period at Rady Children's Hospital of San Diego. Surgical landmarks for this extradural approach were based on the Fukushima dual-fan model, which defines the rhomboid based on the following anatomical structures: 1) the junction of the greater superficial petrosal nerve (GSPN) and mandibular branch of the trigeminal nerve; 2) the lateral edge of the porus trigeminus; 3) the intersection of the petrous ridge and arcuate eminence; and 4) the intersection of the GSPN, geniculate ganglion, and arcuate eminence. The boundaries of maximal bony removal for this approach are the clivus inferiorly below the inferior petrosal sinus; unroofing of the internal auditory canal posteriorly; skeletonizing the geniculate ganglion, GSPN, and internal carotid artery laterally; and drilling under the Gasserian ganglion anteriorly. This extradural petrosectomy allowed for an approach to all lesions from an area posterolateral to the basilar artery near its junction with cranial nerve (CN) VI, superior to the anterior inferior cerebellar artery and lateral to the origin of CN V. Retraction of the mandibular branch of the trigeminal nerve during this approach allowed avoidance of the region involving CN IV and the superior cerebellar artery. RESULTS Eight pediatric patients (4 girls and 4 boys, mean age of 13.2 ± 4.6 years) with hemorrhagic cavernomas involving the lateral pons and extension to the pial surface were treated using the surgical approach described above. Seven cavernomas were completely resected. In the eighth patient, a second peripheral lesion was not resected with the primary lesion. One patient had a transient CN VI palsy, and 2 patients had transient trigeminal hypesthesia/dysesthesia. One patient experienced a CSF leak that was successfully treated by oversewing the wound. CONCLUSIONS The extended middle fossa approach can be used for resection of lateral pontine hemorrhagic cavernomas with minimal morbidity in the pediatric population.
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http://dx.doi.org/10.3171/2017.10.PEDS17381DOI Listing
April 2018

Atrial Fibrillation Ablation and its Impact on Stroke.

Curr Treat Options Cardiovasc Med 2018 Jan 24;20(1). Epub 2018 Jan 24.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT, USA.

Atrial fibrillation (AF) is a commonly encountered arrhythmia, which is not yet fully understood. Catheter ablation has shown to be an effective strategy for rhythm management and several small or retrospective studies have shown that stroke rates are decreased in ablated AF patients compared to those medically managed. Several studies even show that ablation returns stroke risk to that of non-AF patients. Large scale, prospective trials will further illuminate this connection and provide mechanistic understanding of the role of the procedure versus the process of selection for the procedure and peri- and post-procedural therapy and management. Furthermore, modification of risk factors associated with AF show a significant increase in the sustained success of AF ablation and can also moderate the progression of AF.
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http://dx.doi.org/10.1007/s11936-018-0596-0DOI Listing
January 2018

The role of interventricular conduction delay to predict clinical response with cardiac resynchronization therapy.

Heart Rhythm 2017 12;14(12):1748-1755

Intermountain Heart Institute, Murray, Utah.

Background: Pacing at sites with late electrical activation or greater interventricular delay is associated with improvement in measures of cardiac resynchronization therapy (CRT) response, primarily reverse remodeling. However, little is known about whether such lead positions improve heart failure (HF) clinical outcomes.

Objective: The purpose of this study was to assess the association between interventricular electrical delay and HF clinical outcomes.

Methods: The Pacing Evaluation-Atrial SUpport Study was a multicenter randomized trial of patients undergoing CRT-defibrillator implantation. Interventricular delay was measured as the unpaced right ventricle-left ventricle (RV-LV) interval in sinus rhythm. The HF clinical composite score was the primary end point. In addition, the time to first HF hospitalization or death was measured and events were adjudicated by a blinded core laboratory. The cohort was divided at the median RV-LV interval into short (<67 ms) and long (≥67 ms) subgroups. In addition, receiver operating characteristic curves were constructed to identify the optimal cutoff of the RV-LV interval and spline analysis was performed to assess RV-LV interval as a continuous variable.

Results: A total of 1342 patients were included in this study. The clinical composite score at 1 year differed between groups, with more patients improving and fewer patients worsening in the long RV-LV group (P = .014). The time to first HF hospitalization or mortality also differed with a lower risk of an event in the long RV-LV group (hazard ratio 0.62; P = .002). Multivariate analysis showed that RV-LV time (hazard ratio 0.71; P = .038) and sex were independent predictors of this outcome.

Conclusion: Baseline interventricular delay is a strong independent predictor of clinical response to CRT.
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http://dx.doi.org/10.1016/j.hrthm.2017.10.016DOI Listing
December 2017

Five-year impact of catheter ablation for atrial fibrillation in patients with a prior history of stroke.

J Cardiovasc Electrophysiol 2018 02 13;29(2):221-226. Epub 2017 Dec 13.

Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT, USA.

Background: Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach. Patients with a prior history of a stroke (CVA) represent a unique high-risk population for recurrent thromboembolic events. The role of antiarrhythmic treatment on the natural history of stroke recurrence in these patients is not fully understood.

Methods: Three patient groups with a prior CVA and 5 years of follow-up were matched 1:3:3 by propensity score (±0.01): AF ablation patients receiving their first ablation (n  =  139), AF patients that did not receive an ablation (n  =  416), and CVA patients without clinical AF (n  =  416). Prior CVA was determined by medical chart review. Patients were followed for outcomes of recurrent CVA, heart failure, and death.

Results: The average age of the population was 69 ± 11 years and 51% male. AF ablation patients had higher rates of hypertension and heart failure (P < 0.0001), but diabetes prevalence was similar between the groups (P  =  0.5). Note that 5-year risk of CVA (HR  =  2.26, P < 0.0001) and death (HR  =  2.43, P < 0.0001) were higher in the AF, no ablation group compared those that were ablated. When comparing AF, ablation to no AF patients, there was not a significant difference in 5-year risk of for CVA (HR  =  0.82, P  =  0.39) and death (HR  =  0.92, P  =  0.70); however, heart failure risk was increased (HR  =  3.08, P  =  0.001).

Conclusion: In patients with AF and a prior CVA, patients undergoing ablation have lower rates of recurrent stroke compared to AF patients not ablated. Although the full mechanisms of benefit are unknown, as CVA rates are similar to patients without AF these data are suggestive of a potential altering of the natural history of disease progression.
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http://dx.doi.org/10.1111/jce.13390DOI Listing
February 2018
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