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.

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.

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.

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.

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.

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.

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.

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.

Editor's Choice-Clinical impact of delirium and antipsychotic therapy: 10-Year experience from a referral coronary care unit.

BACKGROUND: Little is known about safety of antipsychotic therapy for delirium in the coronary care unit (CCU). Our aim was to examine the effect of delirium and antipsychotic therapy among CCU patients. METHODS AND RESULTS: Pre-study Confusion Assessment Method-Intensive Care Unit (CAM-ICU) criteria were implemented in screening consecutive patients admitted to a referral CCU from 2004-2013. Death status was prospectively ascertained. Of 11,079 study patients, the incidence of delirium was 8.3% ( n=925). Delirium was associated with an increased risk of in-hospital mortality (adjusted odds ratio (OR) 1.49; 95% confidence interval (CI), 1.08-2.08; p=0.02) and one-year mortality among patients who survived from CCU admission (adjusted hazard ratio (HR) 1.46; 95% CI, 1.12-1.87; p=0.005). A total of 792 doses of haloperidol (5 mg/day; interquartile range (IQR) 3-10) or quetiapine (25 mg/day; IQR 13-50) were given to 244 patients with delirium. The clinical characteristics of patients with delirium who did and did not receive antipsychotic therapy were not different (baseline corrected QT (QTc) interval 457±58 ms vs 459±60 ms, respectively; p=0.65). In comparison to baseline, mean QTc intervals after the first and third doses of the antipsychotics were not significantly prolonged in haloperidol (448±56, 458±57 and 450±50 ms, respectively) or quetiapine groups (470±66, 467±68 and 462±46 ms, respectively) ( p>0.05 for all). Additionally, in-hospital mortality (adjusted OR 0.67; 95% CI, 0.42-1.04; p=0.07), ventricular arrhythmia (adjusted OR 0.87; 95% CI, 0.17-3.62; p=0.85) and one-year mortality among the hospital survivors (adjusted HR 0.86; 95% CI 0.62-1.17; p=0.34) were not different in patients with delirium irrespective of whether or not they received antipsychotics. CONCLUSION: In patients admitted to the CCU, delirium was associated with an increase in both in-hospital and one-year mortality. Low doses of haloperidol and quetiapine appeared to be safe, without an increase in risk of sudden cardiac death, in-hospital mortality, or one-year mortality in carefully monitored patients.

Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab.

Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials.