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Abstract Background Implantable cardioverter-defibrillator (ICD) is a well-established therapeutic option associated with decreased mortality in patients with ischemic and non-ischemic cardiomyopathies. However, the indications for patients with chronic Chagas cardiomyopathy (CCC) are not well established since these patients were underrepresented in the trials validating ICD use. Purpose This systematic review and single-arm meta-analysis aims to synthetize the available evidence in the literature on the role and outcomes of ICD in CCC. Methods A systematic search of PubMed, Web of Science, Cochrane, and LILACS registries was performed following PRISMA guidelines. Studies evaluating the response to ICD in CCC were included. There were no language restrictions. Data were collected and synthesized using a meta-analysis of proportions with Freeman-Tukey double-arcsine transformation as needed. Results We included 14 observational studies and 1 randomized clinical trial (RCT), comprising 1315 patients with CCC. Mean age at ICD implantation was 58.2 ± 11.8, 65% were male, and 77% received an ICD for secondary prevention. During a mean follow up of 37.3 ± 37.0 months, the all-cause death rate was 22% (95% CI 15 to 29%; Figure 1A), the cardiovascular death rate was 16% (95% CI 11 to 22%; Figure 1B), the sudden cardiac death rate was 3% (95% CI 2 to 5%), and the non-cardiovascular death rate was 7% (95% CI 2 to 5%). In addition, 55% (95% CI 43 to 67%; Figure 1C) of patients received ≥1 appropriate ICD therapy (shocks or antitachycardia pacing), 8% (95% CI 5 to 12%) received inappropriate ICD shocks, and 23% (95% CI 11 to 37%) experienced electrical storms. Conclusion Despite ICD, the mortality rate in patients with CCC remains unacceptably high, primarily driven by cardiovascular causes, with frequent appropriate ICD therapies and electrical storms. Further studies are needed to better delineate the benefits and risks of ICD therapy in patients with CCC.Figure 1

Abstract Objective To evaluate the effect of erenumab treatment beyond monthly migraine days in patients with high‐frequency episodic migraine who did not respond to at least one previous migraine preventive treatment. Background Reduction in monthly migraine days has been the efficacy standard for migraine preventive treatments; however, it does not fully capture the holistic benefit of the therapy. Erenumab, a monoclonal antibody targeting the calcitonin gene–related peptide pathway, has demonstrated reduction in monthly migraine days and improvement in function in patients with episodic and chronic migraine. Methods In this phase 4, interventional, double‐blind, randomized, placebo‐controlled, multicenter, global study, treatment with erenumab was assessed over 4 months in adults with high‐frequency episodic migraine. The study was conducted at 61 sites located across North America and Europe between September 2020 and October 2023. Patients with ≥1 qualifying oral triptan‐treated migraine attack at baseline were randomized to receive erenumab 140 mg or placebo subcutaneously once monthly. The primary endpoint was change from baseline in mean monthly hours of at least moderate headache pain intensity over months 1, 2, and 3; secondary endpoints included change from baseline in mean monthly function, mean monthly duration of at least moderate pain intensity in migraine attacks, and mean monthly peak migraine pain intensity. Safety outcomes were also assessed. Results Of 512 randomized patients, 510 received erenumab 140 mg ( n = 254) or placebo ( n = 256) once monthly. Demographics and baseline characteristics were balanced between the two treatment arms. Erenumab 140 mg was superior to placebo in reducing duration of moderate or severe headache pain intensity over months 1, 2, and 3 (least squares mean [95% confidence interval {CI}] difference, −7.95 [−11.45, −4.46]; p < 0.001). Compared with placebo, erenumab significantly reduced migraine functional impact as assessed by the four domains of the Migraine Functional Impact Questionnaire, with a least squares mean (95% CI) difference of −7.36 (−10.80, −3.92) for physical functioning, −7.10 (−10.34, −3.87) for usual activities, −6.82 (−10.37, −3.27) for social functioning, and − 7.05 (−10.76, −3.34) for emotional functioning ( p < 0.001 for all domains). Significant reductions with erenumab compared with placebo were also observed in duration of at least moderate pain intensity in residual or break‐through migraine attacks (least squares mean [95% CI] difference, −1.07 [−1.92, −0.22]; p = 0.013) and peak migraine pain intensity (−0.48 [−0.85, −0.11]; p = 0.011). Incidence of grade 3 adverse events was 1.6% with erenumab and 1.2% with placebo; no grade 4 or fatal adverse events were reported in either treatment arm. Conclusion Findings from the EMBRACE study demonstrated that treatment with erenumab in patients with high‐frequency episodic migraine can provide positive therapeutic effects on ictal burden and pain, with residual migraine attacks tending to be shorter and less painful, with less overall impact.

ABSTRACTBackgroundErenumab‐induced medication overuse headache (MOH) remission in participants with chronic migraine (CM) in a prospective, Phase 4, randomized, placebo‐controlled trial with an open‐label treatment period (OLTP). We present 1‐year results from the combined double‐blind treatment period (DBTP) and OLTP for the stratified nonopioid cohort.MethodsParticipants with CM‐MOH were randomized 1:1:1 to subcutaneous 70 or 140 mg erenumab every 4 weeks (QM) or placebo for the initial 24 weeks (DBTP). Those successfully completing DBTP could continue the 28‐week OLTP, maintaining the same erenumab dose received during DBTP or, if receiving placebo, randomly assigned 1:1 to erenumab 70 or 140 mg QM. OLTP endpoints were exploratory.ResultsOverall, 552 participants received erenumab (70 mg, n = 274; 140 mg, n = 278); 95.3% completed OLTP. One‐year MOH relapse in participants who achieved MOH remission at DBTP Month 6 was 2.7% (3/111) and 2.4% (3/124) with erenumab 70 and 140 mg, respectively; absence of MOH at study end was observed in 69.0% (189/274) and 75.5% (210/278) of participants. Sustained MOH absence over 1 year was reported in 60.5% (107/177) and 68.8% (119/173) of participants, respectively. Sustained improvements in measures of headache days, medication days, and function were observed in both groups. No new safety concerns were identified (grade ≥ 3, 35 [6.3%]; serious, 17 [3.1%]; adverse events leading to treatment discontinuation, 5 [0.9%]).ConclusionsErenumab was effective in inducing and sustaining MOH remission and improving function over 1 year. Treatment compliance remained high, with safety events consistent with erenumab's known safety profile.Trial RegistrationNCT03971071

ImportancePatients with chronic migraine and medication overuse headaches (CM-MOH) represent a particularly burdened subpopulation. This trial provides first, to our knowledge, American Academy of Neurology class I evidence for a preventive therapy in CM-MOH.ObjectiveTo assess erenumab efficacy and safety in patients with nonopioid CM-MOH.Design, Settings, and ParticipantsThis randomized, double-blind, parallel-group, placebo-controlled trial took place at 67 centers in North America, Europe, and Australia from October 7, 2019, to November 2, 2022. This report reflects the primary analysis conducted in January 2023, using a database snapshot from December 1, 2022, which contains the complete dataset of the double-blind treatment period (DBTP). Participants included adults with CM-MOH who had 1 or more preventive treatment failure(s). There were 992 participants screened and 620 participants enrolled (584 in nonopioid cohort and 36 in opioid cohort)InterventionsErenumab, 70 mg, 140 mg, or placebo, once monthly for 24 weeks.Main Outcomes and MeasuresThe primary end point was MOH remission at month 6. Secondary end points included change from baseline in mean monthly acute headache medication days (AHMD) at month 6 and sustained MOH remission throughout the DBTP. Safety end points were adverse events and changes in vital signs.ResultsThe primary analysis population included 584 participants in the nonopioid-treated cohort with a mean age of 44 years and 482 participants were female (82.5%). Baseline demographics and disease characteristics were balanced across groups. At month 6, 134 participants in the erenumab, 140 mg group (69.1%) (odds ratio [OR], 2.01; 95% CI, 1.33-3.05; P &amp;lt; .001 vs placebo) and 117 in the erenumab, 70 mg group (60.3%) (OR, 1.37; 95% CI, 0.92-2.05; P = .13 vs placebo) achieved MOH remission vs 102 participants in the placebo group (52.6%). AHMD use was also reduced in the erenumab groups vs placebo. Least squares mean (standard error) change from baseline in average monthly AHMD was –9.4 (0.4) days in the erenumab, 140 mg group (difference from placebo, –2.7; 95% CI, –3.9 to –1.6; P &amp;lt; .001) and –7.8 (0.4) days in the erenumab, 70 mg group (difference from placebo, –1.2; 95% CI, –2.4 to –0.1; P = .03), vs –6.6 (0.4) days in the placebo group. MOH remission throughout the DBTP was sustained in 119 participants (61.3%,) 96 participants (49.5%), and 73 participants (37.6%) in the erenumab, 140 mg, 70 mg, and placebo groups, respectively. Adverse events were consistent with the known safety profile of erenumab. Treatment-emergent adverse events incidence in the combined erenumab group was 66.8% (259 participants; constipation 15.2% (59 participants) and COVID-19 13.9% (54 participants) were most common.Conclusions and RelevanceIn this study, monthly, 140 mg, erenumab injections safely and effectively achieved MOH remission in patients with nonopioid CM-MOH within 6 months.Trial RegistrationClinicalTrials.gov Identifier: NCT03971071

Primary cardiac angiosarcomas (PCA) are highly aggressive malignant heart tumors. Previous reports have shown a poor prognosis regardless of management, and no consensus or guidelines exist. It is necessary to clarify this information since patients with PCA have a short survival. Therefore, we aimed to systematically review clinical manifestations, management, and outcomes. We systematically searched in PubMed, Scopus, Web of Science, and EMBASE. We intended to include cross-sectional studies, case-control studies, cohort studies, and case series that reported clinical characteristics, management, and outcomes of patients with PCA. As a methodological approach, we used the Joanna Briggs Institute Critical Appraisal Checklist for Case Series and the Newcastle-Ottawa Scale for cohorts. We included six studies (five case series, one cohort). The mean/median age ranged from 39 to 48.9 years. Male sex was predominant. The most frequent manifestations were dyspnea (range: 50%-80%), pericardial effusion (29% & 56%), and chest pain (10%-39%). The mean tumor size ranged from 5.8 to 7.2 cm, with the majority of these localized in the right atrium (70-100%). The most common locations of metastasis were the lung (20%-55.6%), liver (10%-22.2%), and bone (10%-20%). Resection (22.9%-94%), and chemotherapy as neoadjuvant or adjuvant (30%-100%) were the most commonly used methods of treatment. Mortality ranged from 64.7% to 100%. PCA often presents late in its course and usually results in poor prognosis. We strongly recommend performing multi-institutional prospective cohorts to better study disease course and treatments to develop consensus, algorithms, and guidelines for this type of sarcoma.