Vision loss reduction with avacincaptad pegol for geographic atrophy: a 12-month post hoc analysis of the GATHER1 and GATHER2 trials.

PURPOSE: To evaluate the impact of reduction in geographic atrophy (GA) lesion growth on visual acuity in the GATHER trials using categorical outcome measures. DESIGN: Randomized, double-masked, sham-controlled phase 3 trials. PARTICIPANTS: Aged ≥50 years with non-center point involving GA and best corrected visual acuity (BCVA) of 25-80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye. METHODS: GATHER1 consisted of 2 parts. In Part 1, 77 patients were randomized 1:1:1 to avacincaptad pegol (ACP) 1 mg, ACP 2 mg, and sham. In Part 2, 209 patients were randomized 1:2:2 to ACP 2 mg, ACP 4 mg, and sham. In GATHER2, patients were randomized 1:1 to ACP 2 mg (n=225) and sham (n=223). A post hoc analysis of 12-month data for pooled ACP 2 mg and sham groups is reported. MAIN OUTCOME MEASURES: Proportion of study eyes that experienced ≥10-, ≥15-, or ≥20-BCVA ETDRS letter loss from baseline to month 12; time-to-event analysis of persistent vision loss of ≥10-, ≥15-, or ≥20-BCVA letters from baseline at ≥2 consecutive visits over 12 months; proportion of study eyes with BCVA loss to a level below driving eligibility threshold at month 12 among those eligible to drive at baseline. RESULTS: Lower proportions of study eyes experienced ≥10-, ≥15-, or ≥20-BCVA letter loss from baseline over 12 months with ACP 2 mg (11.6%, 4.0%, and 1.6%, respectively) vs sham (14.1%, 7.6%, and 4.5%, respectively). There was a reduction in the risk of persistent loss of ≥15-BCVA ETDRS letters with ACP 2 mg (3.4%) vs sham (7.8%) through 12 months. A lower proportion of study eyes treated with ACP 2 mg reached the threshold for driving ineligibility vs sham by 12 months. CONCLUSIONS: Treatment with ACP 2 mg delayed the risk of progression to persistent vision loss (ie, ≥10-, ≥15-, and ≥20-BCVA letter loss or BCVA loss to a level below driving eligibility threshold) vs sham over 12 months.

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.

BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 µL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. FUNDING: Iveric Bio, An Astellas Company.

Takotsubo Syndrome and Complete Heart Block: A Diagnostic and Management Conundrum.

There is increasing evidence that Takotsubo cardiomyopathy behaves more like a highly variable and dangerous syndrome than an isolated cardiomyopathy. In this case report, we describe a case of Takotsubo cardiomyopathy complicated by complete heart block. We discuss the potential mechanisms for its etiology and examine the need for pacemaker placement.

Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.

BACKGROUND/OBJECTIVES: To assess the safety and efficacy of avacincaptad pegol (ACP), a C5 inhibitor, for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) over an 18-month treatment course. SUBJECTS/METHODS: This study was an international, prospective, randomized, double-masked, sham-controlled, phase 2/3 clinical trial that consisted of 2 parts. In part 1, 77 participants were randomized 1:1:1 to receive monthly intravitreal injections of ACP 1 mg, ACP 2 mg, or sham. In part 2, 209 participants were randomized 1:2:2 to receive monthly ACP 2 mg, ACP 4 mg, or sham. The mean rate of change of GA over 18 months was measured by fundus autofluorescence. RESULTS: Compared with their respective sham cohorts, monthly ACP treatment reduced the mean GA growth (square root transformation) over 18 months by 28.1% (0.168 mm, 95% CI [0.066, 0.271]) for the 2 mg cohort and 30.0% (0.167 mm, 95% CI [0.062, 0.273]) for the 4 mg cohort. ACP treatment was generally well tolerated over 18 months, with most ocular adverse events (AEs) related to the injection procedure. Macular neovascularization (MNV) was more frequent in both 2 mg (11.9%) and 4 mg (15.7%) cohorts than their respective sham control groups (2.7% and 2.4%). CONCLUSIONS: Over this 18-month study, ACP 2 mg and 4 mg showed continued reductions in the progression of GA growth compared to sham and continued to be generally well tolerated. A pivotal phase 3 GATHER2 trial is currently underway to support the efficacy and safety of ACP as a potential treatment for GA.

Atrial Septal Aneurysm: An Incidental Finding or a Clinically Significant Anomaly?

Atrial septal aneurysm (ASA) is a condition involving the bulging of the interatrial septum into one or both of the atrial chambers. We present the case of an ASA found on transesophageal echocardiogram in a patient who presented with exertional dyspnea. This case report aims to highlight the growing clinical association of ASA with arterial embolism through various mechanisms and emphasize the unknown aspects of clinical management for such patients. While there are currently no clear recommendations on whether to start anticoagulation after an ASA is diagnosed, many suggest a careful patient-centered approach for such decisions due to the reported increased risk of thromboembolic events. Further studies regarding the significance of ASA and cardioembolic events are needed.

Esophagopericardial Fistula and Pneumopericardium as a Complication of Pulmonary Vein Isolation in a 62-Year-Old Man with Atrial Fibrillation: A Case Report.

BACKGROUND Pulmonary vein isolation is a method of cardiac ablation therapy used to treat irregular heart rhythm, including atrial fibrillation (AF). This report presents a case of esophagopericardial fistula (EPF) and pneumopericardium as a complication of pulmonary vein isolation in a 62-year-old man with AF. CASE REPORT We report the rare case of a 62-year-old man with a medical history of persistent atrial fibrillation status after ablation 3 days prior to his initial Emergency Department visit for chest pain. Acute coronary syndrome was ruled out with normal electrocardiogram, echocardiography, and troponin tests. Fluid overload and sotalol adverse effects were presumed to be the cause of his symptoms. We discontinued sotalol with diuresis and he was discharged home when his chest pain subsided. Nine days later, he returned to the Emergency Department with worsening similar symptoms and was eventually diagnosed with EPF and pneumopericardium on a computed tomography scan of the chest with contrast. He was managed with esophagogastroduodenoscopy and stent placement along with subxiphoid pericardial window and pericardial drain placement. The patient was discharged in stable condition after removing the pericardial drain. At 10-day and 1-month follow-up, he had no recurrent symptoms. CONCLUSIONS This report shows that although EPF with pneumopericardium is a rare complication of pulmonary vein isolation, it should be rapidly diagnosed and treated as a life-threatening emergency.

Symptomatic Myocarditis Post COVID-19 Vaccination.

There are few major adverse events after the coronavirus disease 2019 (COVID-19) vaccination. However, increasing cases of myocarditis and pericarditis are being reported to the Vaccine Adverse Event Reporting System (VAERS) in young people, primarily after the second dose of messenger RNA (mRNA) COVID-19 vaccines. We present a case series of myopericarditis post mRNA (Moderna) and myocarditis post vector-based (Johnson & Johnson) COVID-19 vaccines. We intend to highlight the importance of early diagnosis and treatment of vaccine-related myocarditis to reduce mortality and morbidity.

Complement cascade inhibition in geographic atrophy: a review.

The pathophysiology of dry age-related macular degeneration (AMD) and specifically geographic atrophy (GA) has been linked to the complement cascade. This cascade is part of the innate immune system and is made up of the classical, alternative, and lectin pathways. The pathways comprise a system of plasma and membrane-associated serum proteins that are activated with identification of a nonself entity. A number of these proteins have been implicated in the development and progression of dry AMD. The three pathways converge at C3 and cascade down through C5, making both of these proteins viable targets for the treatment of dry AMD. In addition, there are a number of complement factors, CFB, CFD, CFH, and CFI, which are potential therapeutic targets as well. Several different complement-directed therapeutics are being studied for the treatment of dry AMD with the hope that one of these approaches will emerge as the first approved treatment for GA.

Epileptiform Abnormalities in Acute Ischemic Stroke: Impact on Clinical Management and Outcomes.

PURPOSE: Studies examining seizures (Szs) and epileptiform abnormalities (EAs) using continuous EEG in acute ischemic stroke (AIS) are limited. Therefore, we aimed to describe the prevalence of Sz and EA in AIS, its impact on anti-Sz drug management, and association with discharge outcomes. METHODS: The study included 132 patients with AIS who underwent continuous EEG monitoring >6 hours. Continuous EEG was reviewed for background, Sz and EA (lateralized periodic discharges [LPD], generalized periodic discharges, lateralized rhythmic delta activity, and sporadic epileptiform discharges). Relevant clinical, demographic, and imaging factors were abstracted to identify risk factors for Sz and EA. Outcomes included all-cause mortality, functional outcome at discharge (good outcome as modified Rankin scale of 0-2 and poor outcome as modified Rankin scale of 3-6) and changes to anti-Sz drugs (escalation or de-escalation). RESULTS: The frequency of Sz was 7.6%, and EA was 37.9%. Patients with Sz or EA were more likely to have cortical involvement (84.6% vs. 67.5% P = 0.028). Among the EAs, the presence of LPD was associated with an increased risk of Sz (25.9% in LPD vs. 2.9% without LPD, P = 0.001). Overall, 21.2% patients had anti-Sz drug changes because of continuous EEG findings, 16.7% escalation and 4.5% de-escalation. The presence of EA or Sz was not associated with in-hospital mortality or discharge functional outcomes. CONCLUSIONS: Despite the high incidence of EA, the rate of Sz in AIS is relatively lower and is associated with the presence of LPDs. These continuous EEG findings resulted in anti-Sz drug changes in one-fifth of the cohort. Epileptiform abnormality and Sz did not affect mortality or discharge functional outcomes.

Left Atrial Myxoma Masquerading as Pulmonary Embolism on Electrocardiogram: A Case Report.

Primary cardiac tumors are an incredibly rare finding. Cardiac myxomas are the most primary cardiac tumors that often occur within the left atrium. When left untreated, they pose a high risk of causing hemodynamic collapse by obstruction or can embolize and result in thromboembolic stroke. The presentation of cardiac myxoma varies greatly and can be associated with significant morbidity and mortality when undiagnosed. A careful physical examination and high degree of suspicion is crucial in early diagnosis and intervention. Our team presents a 46-year-old female patient with no significant past medical history that presented to the emergency department with a neurological deficit that was concerning for a transient ischemic attack. Initial laboratory workup and electrocardiogram was suggestive for pulmonary embolism; however, upon evaluation with imaging, the patient was found to have a 1.6 × 3.4 cm mass fixed to the mitral leaflet that was then confirmed on transthoracic echocardiography. Our patient was found to have non-obstructive coronary artery disease on cardiac catheterization and ultimately underwent successful mass resection by cardiothoracic surgery.

Anomalous Coronary Arteries: A Case of Rare and Incidental Findings.

Anomalous coronary artery from the opposite sinus (ACAOS) is an uncommon, yet highly variable anatomical abnormality. These coronary anatomy variants are often discovered incidentally during cardiac catheterization. These variants can be challenging intraoperatively and require adjustment by the operator. We present the case of a 93-year-old female who presented for shortness of breath due to severe mitral regurgitation (MR), who was found to have an anomalous left main coronary artery (LMCA) from the right sinus of Valsalva (RSOV). This asymptomatic finding was managed conservatively and patient underwent successful MitraClip treatment.

Large Right Atrial Myxoma Presenting As Bilateral Pulmonary Embolism.

Myxoma is a rare benign tumor of the heart. Cardiac myxomas are the most common primary cardiac tumor in adults, commonly found within the left atrium. It can occur at any age and is more common in females than males. This case report aims to identify the clinical symptoms of cardiac myxoma, which can be life-threatening if neglected. Here, we present the case of a 30-year-old female with past smoking history. For the past three to four weeks before this hospitalization, her symptoms worsened including shortness of breath with exertion, dry cough, and pleuritic chest pain. Outpatient treatment with antibiotics and nebulizers did not relieve her symptoms. She went to the emergency room and underwent computed tomography of the chest with contrast showing bilateral lower lobe pulmonary emboli and a large mass in the right atrium. Intravenous unfractionated heparin was initiated. A transthoracic echocardiogram confirmed a 3.76 cm × 4.95 cm mass in the right atrium. The patient underwent surgical resection of the right atrial mass the following day and was discharged four days later in a stable condition. Pathology of the mass confirmed atrial myxoma.

Critical Analysis of Outcome Between Ventral and Dorsal Onlay Urethroplasty In Female Urethral Stricture.

OBJECTIVES: To evaluate and compare the 2 surgical approaches of urethral reconstruction for management of refractory female urethral strictures (FUS) in a prospective randomized setting. Early surgical reconstruction is becoming the preferred management strategy for recurrent FUS. Reconstructive techniques have been described as using either dorsal (12-o'clock) or ventral approach (6-o'clock), each with their own advantages. To our best knowledge, a direct comparison between the 2 techniques to prospectively compare outcomes hasn't been made. METHODS: We performed a prospective randomized study in a single tertiary care center on a total of 24 patients, randomizing them into 2 groups of 12 patients each. One group underwent dorsal onlay and other underwent ventral onlay urethroplasty. Preoperative, intraoperative and postoperative outcomes were evaluated and compared for the 2 approaches. RESULTS: There was high success rate (91%) with significant but comparable improvements in flow rates, post void residue and symptomatic outcomes without any major complication. There was 1 recurrence of stricture each in both groups. Important technical differences were noted with easier meatus preservation, lesser bleeding and wider operative field in the ventral approach, while the dorsal approach proving better in distal urethral strictures requiring meatal reconstruction. CONCLUSION: Both approaches of urethroplasty present a very promising modality of management of FUS with comparable outcomes but with important technical differences which must be considered to best tailor the approach for each patient.

An Atypical Presentation of Heroin Inhalation Induced Leukoencephalopathy (Chasing the Dragon).

Heroin leukoencephalopathy is associated with 'Chasing the dragon,' which is a heroin vapour inhalation method that is different from smoking or sniffing heroin. The clinical presentation ranges from mild to severe disease. Mild disease is characterized by inattentiveness and ataxia. In moderate diseases, extrapyramidal symptoms predominate, and finally, severe disease is characterized by generalized motor impairment, with death occurring in two-third of cases. We now report a rare presentation of the disease in a 60-year-old female with a past medical history of heroin abuse who presented to ED with signs and symptoms of confusion and restlessness. MRI brain without contrast showed diffuse symmetric increased intensity signals throughout the white matter. Electroencephalogram (EEG) revealed mild diffuse slowing with no lateralization. The patient was started on Vitamin E and was transferred to a rehab facility with following up neurology as an outpatient.

Unusual Longevity of Edwards Syndrome: A Case Report.

BACKGROUND: Trisomy 18, also known as Edwards syndrome, was first described in the 1960s and is now defined as the second most common trisomy. While this genetic disease has been attributed to nondisjunction during meiosis, the exact mechanism remains unknown. Trisomy 18 is associated with a significantly increased mortality rate of about 5-10% of patients surviving until 1 year of age. We present a case of a 26-year-old female diagnosed with trisomy 18, well outliving her life expectancy, maintaining a stable state of health. CASE PRESENTATION: A 26-year-old female with non-mosaic Edwards syndrome presented to the clinic for follow up after recent hospitalization for aspiration pneumonia. The definitive diagnosis of trisomy 18 was made prenatally utilizing chromosomal analysis and G-banding and fluorescence in situ hybridization (FISH) on cells obtained via amniocentesis. Her past medical history is characterized by severe growth and intellectual limitations; recurrent history of infections, especially respiratory system infections; and a ventricular septal defect (VSD) that was never surgically repaired. She remains in good, stable health and is under close follow-up and monitoring. CONCLUSIONS: Despite the fact that Edwards syndrome carries a significantly high mortality rate due to several comorbidities, recent literature including this case report has identified patients surviving into adulthood. Advancements in early detection and parent education have likely allowed for these findings. We aim to present a case of an adult with trisomy 18, living in stable condition, with an importance on medical follow-up.

Lambl's Excrescences Associated With Left Frontal Ischemic Stroke: A Case Report.

Lambl's excrescences (LEs) are thin filiform strands of connective tissue found on the closure line of valves. Their exact etiology is unknown, and most of them are typically asymptomatic. We present a case of a 33-year-old African American male with a history of right upper extremity weakness that resolved on its own within a few minutes. On physical examination, no focal neurologic deficit was observed. MRI brain showed a tiny curvilinear focus of restricted diffusion with subtle T2-FLAIR hyperintensity in the left frontal/insular region, indicating a recent cortical infarct. Transesophageal echocardiogram (TEE) was performed as a part of cryptogenic stroke workup, which showed LE on aortic valve leaflet tips. Our patient had elevated blood pressure (BP) on arrival; however, in LE's presence, the embolic phenomena of stroke cannot be excluded. In conclusion, this case adds to a limited number of cases with such cardioembolic phenomena, which will help in further illustrating and highlighting the need for more prospective studies to establish a causal relationship between LE and cardioembolic strokes.

Transcatheter Edge-to-Edge Repair for Primary (Degenerative) Mitral Regurgitation: Registries and Trials.

The MitraClip is the only approved transcatheter edge-to-edge repair device that is commercially available for the treatment of severe, symptomatic, primary (degenerative) mitral regurgitation in patients deemed to be at prohibitive risk by a heart team. Transcatheter edge-to-edge repair can be safely performed with a low rate of periprocedural adverse events despite a predominantly elderly patient population with multiple comorbidities. Transcatheter edge-to-edge repair is associated with improvement in mitral regurgitation severity; left ventricular dimensions and remodeling; heart failure rehospitalizations; and, in high-risk groups, an improvement in survival compared with medical therapy.

Large Epicardial Hematoma After Percutaneous Coronary Intervention: Multimodality Imaging.

Epicardial hematoma can manifest immediately or within a few minutes to hours after coronary intervention. Review of angiogram after the diagnosis of hematoma, in our case, showed deep distal positioning of a non-polymer jacketed wire, which is the most likely cause of the adverse outcome. Multimodality imaging is critical for diagnosis and management of such cases.