Distribution of Myocardial Fibrosis in Patients with Non-Ischemic Cardiomyopathy and Ventricular Tachycardia Based on Genetic Variant.

BACKGROUND: Many genetic non-ischemic dilated cardiomyopathies (NICM) cause ventricular tachycardias (VT) originating from scar substrate identified as areas of low electrogram voltage. Substrate locations vary and the causes of scar are not well defined. OBJECTIVE: This study evaluated VT substrate locations in genetic NICM patients undergoing VT ablation to evaluate spatial relationships between specific variants and substrate locations. METHODS: In this retrospective case series analysis, 32 patients (age 55 +/- 16 years, 94% male, left ventricular ejection fraction 34 +/- 13%) with genetic NICM referred for VT ablation between October 2018 and November 2022 at a single medical center were evaluated. Scar locations were defined as areas of low unipolar/ bipolar voltage. RESULTS: Of the thirty-two patients evaluated, mutations in TTN (n=11 of 32), LMNA (n=6 of 32), PKP2 (n=5 of 32), MYBPC3 (n=3 of 32), DSP (n=2 of 32), TTR (n=1 of 32), FLNC (n=1 of 32), AGL (n=1 of 32), DES (n=1 of 32), DSG2 (n=1 of 32), were observed. Substrates associated with mutations in TTN were only observed in basal subregions, predominantly anterior (100%), and septal (50%) regions. LMNA mutations were associated with fibrosis in mid inferolateral (60%) and apical inferolateral (60%) regions. Substrate location for individuals with PKP2 mutations were solely observed in the right ventricle, predominantly basal inferolateral regions. CONCLUSION: Understanding spatial relationships between genetic variants causing NICM and VT substrate locations can help lead to generalizable regions in patients with genetically related NICM presenting in VT which can be investigated during ablation procedures.

Can Intracardiac Echocardiography Reduce Steam Pops During Half-Normal Saline Irrigated Radiofrequency Ablation?

BACKGROUND: Irrigated radiofrequency ablation with half-normal saline can potentially increase lesion size but may increase the risk of steam pops with the risk of emboli or perforation. We hypothesized that pops would be preceded by intracardiac echocardiography (ICE) findings as well as a large impedance fall. METHODS: In 100 consecutive patients undergoing endocardial ventricular arrhythmia radiofrequency ablation with half-normal saline, we attempted to observe the ablation site with ICE. Radiofrequency ablation power was titrated to a 15 to 20 Ohm impedance fall and could be adjusted for tissue whitening and increasing bubble formation on ICE. Steam pops were defined as audible or a sudden explosion of microbubbles on ICE. RESULTS: Of 2190 ablation applications in 100 patients (82% cardiomyopathy, 50% sustained ventricular tachycardia), pops occurred during 43 (2.0%) applications. Sites with pops had greater impedance decreases of 18 [14, 21]% versus 13 [10, 17]% (P<0.001). ICE visualized 1308 (59.7%) radiofrequency sites, and fewer pops occurred when ICE visualized the radiofrequency ablation site (1.4%) compared with without ICE visualization (2.8%; P=0.016). Of the 18 ICE-visible pops, 7 (39%) were silent but recognized as an explosion of bubbles on ICE. With ICE, 89% of pops were preceded by either tissue whitening or a sudden increase in bubbles. In a multivariable model, tissue whitening and a sudden increase in bubbles were associated with steam pops (odds ratio, 7.186; P=0.004, and odds ratio, 29.93; P<0.001, respectively), independent of impedance fall and power. There were no pericardial effusions or embolic events with steam pops. CONCLUSIONS: Steam pops occurred in 2% of half-normal saline radiofrequency applications titrated to an impedance fall and are likely under-recognized without ICE. On ICE, steam pops are usually preceded by tissue whitening or a sudden increase in bubble formation, which can potentially be used to adjust radiofrequency application to help reduce pops.

Perspectives of wheelchair users with chronic spinal cord injury following a walking program using a wearable robotic exoskeleton.

PURPOSE: To examine the perspectives of wheelchair users with spinal cord injury (WUSCI) regarding their participation in a 16-week walking program using a wearable robotic exoskeleton (WRE); and explore concerns and expectations regarding potential use of this device and intervention in the context of a home or community-based adapted physical activity program. METHOD: Semi-structured interviews were conducted using a narrative research, 3 weeks post-intervention. Thematic analysis resulted in 6 themes and 21 subthemes. RESULTS: Seven men and 4 women aged between 32 and 72 years were interviewed; 8 of them had a complete SCI. After the walking program, WUSCI reported positive psychological aspects (having fun and motivation) and experiencing improvements in physical aspects (strength, endurance, balance and flexibility, blood circulation and intestinal transit). The structural aspects of the WRE device were acceptable in a lab with research personnel (appearance, size, weight, and comfort). Participants had concerns about safety on uneven surfaces, and possibility of falling. They expressed the desire to use the WRE for more life habits than just walking. CONCLUSION: This is the first study in which WUSCI report that the WRE should be implemented in initial rehabilitation. Lack of availability for community use after rehabilitation remains a concern.

Participation in a walking training program using a wearable robotic exoskeleton, 1-3 times weekly over several weeks, may be well tolerated and provide physical and psychological benefits for wheelchair users with spinal cord injuries.Using a robotic exoskeleton during initial rehabilitation may be well received and help with regaining strength, endurance, balance, and flexibility as well as promoting blood circulation and intestinal transit.The use of the wearable robotic exoskeleton always needs supervision of a clinician for walking and can't be used independently by wheelchair users; there is no possibility for hands free for household tasks (e.g., washing floors, accessing cupboards or reaching shelves, using stairs), and for recreation (e.g., exercising, taking walks, cultural activities, concerts).

Successful Confirmation of Dual Genital Herpes Co-Infection with Herpes Simplex Virus 1 and Herpes Simplex Virus 2 Using Unbiased Metagenomic Next-Generation Sequencing.

Dual co-infection with both HSV-1 and HSV-2 is rare, with few cases reported in the literature. In this case report, we describe the successful use of unbiased metagenomic next-generation sequencing (mNGS) as a rapid and alternative method for confirming dual genital herpes co-infection. Our case involves a 74-year-old woman who presented with genital lesions and initially tested positive for both HSV-1 and HSV-2 via the Luminex ARIES HSV 1&2 assay. The entire mNGS process, from nucleic acid extraction to result analysis, was completed in less than 48 h. Using mNGS, we identified mapped reads specific to either HSV-1 or HSV-2 and screened the sequences to rule out mis-genotyping by the Luminex ARIES assay. Notably, the generated sequences can reveal sequence variations within multiple gene regions, demonstrating the potential of mNGS for identifying novel HSV-1 and HSV-2 variants. Our findings suggest that mNGS can serve as a rapid and reliable alternative confirmatory method for dual genital herpes infections, providing valuable information to guide appropriate treatment options for patients. By eliminating the need for prior knowledge of causative agents, mNGS offers an unbiased approach for detecting and characterizing viral co-infections.

Design of Instructional Videos for People with Autism Who Want to Learn About Grocery Store Work: A Community, Business, Educational and Health Partnership.

To facilitate the integration of people with autism into the food industry labour market, this cross sectoral project aimed to design, validate and test instructional videos to concretely demonstrate various tasks in the grocery store, and to probe interest and assess knowledge about these tasks. Results are the delivery of 21 instructional videos validated for individuals with autism and 21 for mentors in grocery.

Catheter Ablation of Atrial Fibrillation in Adult Congenital Heart Disease: Procedural Characteristics and Outcomes.

BACKGROUND: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described. METHODS: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use. RESULTS: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14-69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non-pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%-45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00-1.06] per 1 mL/m2 increment; P=0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21-0.90]; P=0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8-37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs. CONCLUSIONS: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation.

Helping Patients With Chronic Conditions Overcome Challenges of High-Deductible Health Plans: Mixed Methods Study.

BACKGROUND: A growing number of Americans are enrolled in high-deductible health plans (HDHPs). Enrollees in HDHPs, particularly those with chronic conditions, face high out-of-pocket costs and often delay or forgo needed care owing to cost. These challenges could be mitigated by the use of cost-conscious strategies when seeking health care, such as discussing costs with providers, saving for medical expenses, and using web-based tools to compare prices, but few HDHP enrollees engage in such cost-conscious strategies. A novel behavioral intervention could enable HDHP enrollees with chronic conditions to adopt these strategies, but it is unknown which intervention features would be most valued and used by this patient population. OBJECTIVE: This study aimed to assess preferences among HDHP enrollees with chronic conditions for a novel behavioral intervention that supports the use of cost-conscious strategies when planning for and seeking health care. METHODS: In an exploratory sequential mixed methods study among HDHP enrollees with chronic conditions, we conducted 20 semistructured telephone interviews and then surveyed 432 participants using a national internet survey panel. Participants were adult HDHP enrollees with diabetes, hypertension, coronary artery disease, chronic obstructive pulmonary disease, or asthma. The interviews and survey assessed participants' health care experiences when using HDHPs and their preferences for the content, modality, and frequency of use of a novel intervention that would support their use of cost-conscious strategies when seeking health care. RESULTS: Approximately half (11/20, 55%) of the interview participants reported barriers to using cost-conscious strategies. These included not knowing where to find information and worrying that the use of cost-conscious strategies would be very time consuming. Most (18/20, 90%) interviewees who had discussed costs with providers, saved for medical expenses, or used web-based price comparison tools found these strategies to be helpful for managing their health care costs. Most (17/20, 85%) interviewees expressed interest in an intervention delivered through a website or phone app that would help them compare prices for services at different locations. Survey participants were most interested in learning to compare prices and quality, followed by discussing costs with their providers and putting aside money for care, through a website-based or email-based intervention that they would use a few times a year. CONCLUSIONS: Regular use of cost-conscious strategies could mitigate financial barriers faced by HDHP enrollees with chronic conditions. Interventions to encourage the use of cost-conscious strategies should be delivered through a web-based modality and focus on helping these patients in navigating their HDHPs to better manage their out-of-pocket spending.

Novel insights into the substrate involved in maintenance of ventricular fibrillation: results from continuous multipolar mapping in a canine model.

BACKGROUND: While the triggers for ventricular fibrillation (VF) are well-known, the substrate required for its maintenance remains elusive. We have previously demonstrated dynamic spatiotemporal changes across VF from electrical induction of VF to asystole. Those data suggested that VF drivers seemed to reside in the distal RV and LV. However, signals from these areas were not recorded continuously. The aim of this study was to map these regions of significance with stationary basket electrodes from induction to asystole to provide further insights into the critical substrate for VF rhythm sustenance in canines. METHODS: In six healthy canines, three multipolar basket catheters were positioned in the distal right ventricle (RV), RV outflow tract, and distal left ventricle (LV), and remained in place throughout the study. VF was induced via direct current application from an electrophysiologic catheter. Surface and intracardiac electrograms were recorded simultaneously and continuously from baseline, throughout VF, and until asystole, in order to get a complete electrophysiologic analysis of VF. Focused data analysis was also performed via two defined stages of VF: early VF (immediately after induction of VF to 10 min) and late VF (after 10 min up to VF termination and asystole). RESULTS: VF was continuously mapped for a mean duration of 54 ± 9 min (range 42-70 min). Immediately after initiation of VF in the early phase, the distal LV region appeared to drive the maintenance of VF. Towards the terminal stage of VF, the distal RV region appeared to be responsible for VF persistence. In all canines, we noted local termination of VF in the LV, while VF on surface ECG continued; conversely, subsequent spontaneous termination of VF in the RV was associated with termination of VF on surface ECG into a ventricular escape rhythm. Continuous mapping of VF showed trends towards an increase in peak-to-peak ventricular electrogram cycle length (p = 0.06) and a decrease in the ventricular electrogram amplitude (p = 0.06) after 40 min. Once we could no longer discern surface QRS activity, we demonstrated local ventricular myocardial capture in both the RV and LV but could not reinitiate sustained VF despite aggressive ventricular burst pacing. CONCLUSIONS: This study describes the evolution of VF from electrical initiation to spontaneous VF termination without hemodynamic support in healthy canines. These data are hypothesis-generating and suggest that critical substrate for VF maintenance may reside in both the distal RV and LV depending on stage of VF. Further studies are needed to replicate these findings with hemodynamic support and to translate such findings into clinical practice. Ventricular fibrillation maintenance may be dependent on critical structures in the distal RV. ECG: electrocardiogram; LV: left ventricle; RV: right ventricle; RVOT: right ventricular outflow tract; VF: ventricular fibrillation.

A Proposed Algorithm for Managing Cerebral Proliferative Angiopathy.

OBJECTIVE: Cerebral proliferative angiopathy (CPA) is a rare disease, characterized by a large vascular nidus, diffuse angiogenesis, and intermingled normal brain tissue. Conservative treatment, endovascular intervention, indirect revascularization, and radiotherapy have been applied to treat this disease. However, some cases deteriorate even after non-conservative treatment, and there has been no standard of treatment for this disease so far. In order to build a better treatment strategy, we review literature, present our case and propose an algorithm for managing CPA. METHODS: Following the PRISMA principle, we systemically reviewed literature discussing CPA. A case successfully managed with multi-modal treatment is also illustrated. RESULTS: A total of 23 articles with 74 cases of CPA were found. Thirty-three patients received single-modal management. These 33 cases include 24 receiving endovascular intervention, 7 receiving indirect revascularization, and 2 receiving radiotherapy. Three of the 33 patients deteriorated clinically, and 1 expired. We present a 6-year-old boy with left hemispheric CPA receiving indirect revascularization, followed by 2 consecutive courses of stereotactic radiosurgery targeting arteriovenous shunts in the left basal ganglia and arteriovenous shunts around the olfactory groove. In the follow-up period of more than 4 years, good collateral formation, improved perilesional perfusion, CPA shrinkage, and symptom relief were all achieved. CONCLUSIONS: Based on our literature review and case, we propose an algorithm for the management of CPA and emphasize that multi-modal treatment is necessary for most CPA cases.

Ventricular nanosecond pulsed electric field delivery using active fixation leads: a proof-of-concept preclinical study.

BACKGROUND: Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept. METHODS: In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month. RESULTS: Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes. CONCLUSIONS: Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads.

Paroxysmal supine hypoxaemia with hyperthyroidism and atrial fibrillation: a case report of a diagnostic challenge.

Background: A patent foramen ovale (PFO) is a persistent embryonic defect in the interatrial septum. Platypnoea-orthodeoxia syndrome is characterized by positional hypoxaemia that is most commonly due to right-to-left shunting through a PFO. Dynamic right-to-left shunting through a PFO can also exacerbate positional hypoxaemia without platypnea-orthodeoxia syndrome. Case summary: A 78-year-old woman with hyperthyroidism and paroxysmal atrial fibrillation (AF) presented with positional hypoxaemia exacerbated by supine positioning. Diagnostic testing revealed intermittent right-to-left shunting through a PFO triggered by worsening atrial functional tricuspid regurgitation and elevated right atrial pressures. Diuresis, rate control, and thyroidectomy initially led to resolution of positional hypoxaemia, but recurrent AF episodes triggered right-to-left shunting with recurrent desaturation. Left atrial and cavo-tricuspid isthmus ablation led to restoration of normal sinus rhythm and resolution of positional hypoxaemia without PFO closure. Discussion: The clinical presentation of intermittent intracardiac right-to-left shunting can mimic decompensated heart failure with pulmonary oedema. Persistent hypoxaemia out of proportion to the degree of pulmonary oedema and minimally responsive to supplemental O2 should raise suspicion for right-to-left shunt aetiology. Positional arterial blood gases can facilitate the diagnostic evaluation of refractory hypoxaemia in cases of suspected shunting. Diagnostic imaging for PFO detection includes both transthoracic and transesophageal echocardiography with Valsalva manoeuver and agitated saline injection. Closure of a PFO for management of arterial deoxygenation syndromes should not be performed before treating other causes of arterial deoxygenation and optimizing factors that may exacerbate shunting across the PFO.

PTH 1-34 Replacement Therapy Has Minimal Effect on Quality of Life in Patients With Hypoparathyroidism.

In addition to hypocalcemia, patients with hypoparathyroidism report poor quality of life (QOL), complaining of fatigue and "brain fog." Parathyroid hormone (PTH) therapy can effectively manage hypocalcemia; however, the effects of PTH treatment on QOL are unclear. Thirty-one patients with hypoparathyroidism were treated in an open-label study with full replacement subcutaneous PTH 1-34 twice daily for up to 5.3 years, with individualized fine-dosing titration. Prior to initiation of PTH 1-34, conventional therapy was optimized. The 36-Item Short Form (SF-36) Health Survey, Fatigue Symptom Inventory (FSI), and 6-minute walk test (6MWT) were assessed at PTH start (baseline), every 6 months on PTH, and after PTH discontinuation. The SF-36 assesses physical function (PF), physical role limitations (RP), bodily pain (BP), general health (GH), vitality (VT), emotional role limitations (RE), social function (SF), and mental health (MH). Compared to population norms, patients at baseline had lower scores in RP, GH, VT, and MH (p < 0.05), consistent with impaired QOL. With PTH therapy, only GH at 6 months and VT at 12 months improved (p < 0.05). At the last treatment time point, RP, VT, and SF improved compared to baseline (p < 0.05). However, follow-up scores were unchanged from baseline or last PTH treatment, except for SF, which had decreased at follow-up compared to on-PTH (p < 0.05). On the FSI, there were no changes in fatigue frequency; perceived interference was improved at 12 and 18 months and composite severity was improved only at 60 months (p < 0.05). The 6MWT measures did not change. In conclusion, hypoparathyroidism is associated with decreased QOL. Despite the bias in open-label studies to predict improvements in QOL, PTH therapy had limited and non-sustained effects on QOL, inconclusive changes in fatigue experience, and no change in the 6MWT. Although PTH 1-34 can adequately manage the hypocalcemia in hypoparathyroidism, its effects on QOL appear to be minimal. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Heart Watch Study: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04468321.

Cardiovascular Considerations in Coronavirus Disease 2019 with a Special Focus on Arrhythmia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, has significant cardiovascular manifestations. Several studies to date have suggested worse outcomes occur in patients with elevated troponin levels. Among hospitalized patients in Wuhan, China, arrhythmias including malignant ventricular arrhythmia have been reported. Conduction abnormalities in COVID-19 patients have also been described. Additionally, there have been concerns raised regarding COVID-19-related myocarditis, of which reported biopsy-proven cases to date appear to be rare. In this review, we address COVID-19 concerns for the cardiologist and electrophysiologist, including arrhythmia and conduction abnormalities, myocarditis, and arrhythmia in critically ill patients; angiotensin-converting enzyme 2 in cardiac patients; hypercoagulability; and the drug properties of hydroxychloroquine as one of the potential therapies under review.

Trends in reported industry payments to physicians practicing cardiac electrophysiology from 2013 to 2018 in the United States.

INTRODUCTION: The need for transparency in financial relationships in the healthcare system, has culminated in Open Payments database, managed by the Center for Medicare and Medicaid Services (CMS). Since its inception in 2013, the trend in such payments to physicians practicing cardiac electrophysiology was not examined. METHODS AND RESULTS: Payment information reported to CMS from January 2013 to December 2018 was obtained from the publicly available Open Payments data set using the online query tool. The data were analyzed by an individual provider and by state. An in-depth analysis of payments in the year 2018 payments was performed. From 2014 to 2018, there was an 18% increase in the total number of payments reported from 88 877 payments in 2014 to 105 000 in 2018. Despite the increase in the total number of payments reported, the average payment steadily decreased over time, resulting in an overall reduction in the total amount of payments from 2014 to 2018 ($34.9 million to $28.2 million). Payments to the top 5% of individual recipients have also decreased over this time. In 2018, 2888 unique providers received reportable payments, a total of 105 000 payments, with a median payment amount of $1378 (interquartile range: $165-$5781). The majority of these payments were for food and beverage (82%) and travel/lodging (10%). The top five payers include Boston Scientific, Medtronic Vascular, Abbott Laboratories, Janssen Pharmaceuticals, and Biotronik. CONCLUSION: Among cardiac electrophysiologists, there is increased reporting of payments in the Open Payments program over time, with a notable decrease in the payment amount.

The Outcome of TGFß Antagonism in Metastatic Breast Cancer Models In Vivo Reflects a Complex Balance between Tumor-Suppressive and Proprogression Activities of TGFß.

PURPOSE: TGFßs are overexpressed in many advanced cancers and promote cancer progression through mechanisms that include suppression of immunosurveillance. Multiple strategies to antagonize the TGFß pathway are in early-phase oncology trials. However, TGFßs also have tumor-suppressive activities early in tumorigenesis, and the extent to which these might be retained in advanced disease has not been fully explored. EXPERIMENTAL DESIGN: A panel of 12 immunocompetent mouse allograft models of metastatic breast cancer was tested for the effect of neutralizing anti-TGFß antibodies on lung metastatic burden. Extensive correlative biology analyses were performed to assess potential predictive biomarkers and probe underlying mechanisms. RESULTS: Heterogeneous responses to anti-TGFß treatment were observed, with 5 of 12 models (42%) showing suppression of metastasis, 4 of 12 (33%) showing no response, and 3 of 12 (25%) showing an undesirable stimulation (up to 9-fold) of metastasis. Inhibition of metastasis was immune-dependent, whereas stimulation of metastasis was immune-independent and targeted the tumor cell compartment, potentially affecting the cancer stem cell. Thus, the integrated outcome of TGFß antagonism depends on a complex balance between enhancing effective antitumor immunity and disrupting persistent tumor-suppressive effects of TGFß on the tumor cell. Applying transcriptomic signatures derived from treatment-naïve mouse primary tumors to human breast cancer datasets suggested that patients with breast cancer with high-grade, estrogen receptor-negative disease are most likely to benefit from anti-TGFß therapy. CONCLUSIONS: Contrary to dogma, tumor-suppressive responses to TGFß are retained in some advanced metastatic tumors. Safe deployment of TGFß antagonists in the clinic will require good predictive biomarkers.

Cangrelor Bridging Within 6 Months of a Drug-Eluting Stent in a Patient for Emergency Cervical Spine Surgery: A Case Report.

The recommended duration of dual antiplatelet therapy after drug-eluting stent placement presents a dilemma for patients with recent stenting who require urgent or emergency noncardiac surgery. We present the case of a patient with recent drug-eluting stent placement (<6 months) on dual antiplatelet therapy who underwent successful emergency cervical spine surgery with antiplatelet therapy bridged using cangrelor, an intravenous P2Y12 inhibitor antiplatelet agent. Our experience illustrates the multidisciplinary approach to a patient with high thrombotic and bleeding risk who underwent neurosurgery off both aspirin and a P2Y12 inhibitor.

Outcomes of Catheter Ablation of Ventricular Tachycardia Based on Etiology in Nonischemic Heart Disease: An International Ventricular Tachycardia Ablation Center Collaborative Study.

OBJECTIVES: This study sought to characterize ventricular tachycardia (VT) ablation outcomes across nonischemic cardiomyopathy (NICM) etiologies and adjust these outcomes by patient-related comorbidities that could explain differences in arrhythmia recurrence rates. BACKGROUND: Outcomes of catheter ablation of VT in patients with NICM could be related to etiology of NICM. METHODS: Data from 2,075 patients with structural heart disease referred for catheter ablation of VT from 12 international centers was retrospectively analyzed. Patient characteristics and outcomes were noted for the 6 most common NICM etiologies. Multivariable Cox proportional hazards modeling was used to adjust for potential confounders. RESULTS: Of 780 NICM patients (57 ± 14 years of age, 18% women, left ventricular ejection fraction 37 ± 13%), underlying prevalence was 66% for dilated idiopathic cardiomyopathy (DICM), 13% for arrhythmogenic right ventricular cardiomyopathy (ARVC), 6% for valvular cardiomyopathy, 6% for myocarditis, 4% for hypertrophic cardiomyopathy, and 3% for sarcoidosis. One-year freedom from VT was 69%, and freedom from VT, heart transplantation, and death was 62%. On unadjusted competing risk analysis, VT ablation in ARVC demonstrated superior VT-free survival (82%) versus DICM (p ≤ 0.01). Valvular cardiomyopathy had the poorest unadjusted VT-free survival, at 47% (p < 0.01). After adjusting for comorbidities, including age, heart failure severity, ejection fraction, prior ablation, and antiarrhythmic medication use, myocarditis, ARVC, and DICM demonstrated similar outcomes, whereas hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis had the highest risk of VT recurrence. CONCLUSIONS: Catheter ablation of VT in NICM is effective. Etiology of NICM is a significant predictor of outcomes, with ARVC, myocarditis, and DICM having similar but superior outcomes to hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis, after adjusting for potential covariates.

Efficacy of Warfarin Anticoagulation and Incident Dementia in a Community-Based Cohort of Atrial Fibrillation.

OBJECTIVE: To study the association between time in therapeutic range (TTR) during warfarin therapy and risk of dementia in a population-based cohort of incident atrial fibrillation (AF). PATIENTS AND METHODS: We conducted an observational population-based study of 2800 nondemented patients with incident AF from January 1, 2000, through December 31, 2010. The association of incident dementia with warfarin therapy and TTR was examined using Cox proportional hazards regression models. RESULTS: Mean patient age was 71.2 years; 53% were men (n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a mean ± SD follow-up of 5.0±3.7 years. After adjusting for confounders, warfarin therapy was associated with a reduced incidence of dementia (hazard ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest quartiles of TTR were associated with lower risk of dementia. A 10% increase in TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI, 0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were associated with decreased risk of dementia. CONCLUSION: In the community, warfarin therapy for AF is associated with a 20% reduction in risk of dementia. Increasing TTR on warfarin is associated with reduced risk of dementia. The risk of dementia was reduced with a reduction in time spent in subtherapeutic and supratherapeutic international normalized ratio range. Effective anticoagulation may prevent cognitive impairment in patients with AF.