Effect of Personalized Accelerated Pacing on Quality of Life, Physical Activity, and Atrial Fibrillation in Patients With Preclinical and Overt Heart Failure With Preserved Ejection Fraction: The myPACE Randomized Clinical Trial.

Importance: Patients with heart failure with preserved ejection fraction (HFpEF) with a pacemaker may benefit from a higher, more physiologic backup heart rate than the nominal 60 beats per minute (bpm) setting. Objective: To assess the effects of a moderately accelerated personalized backup heart rate compared with 60 bpm (usual care) in patients with preexisting pacemaker systems that limit pacemaker-mediated dyssynchrony. Design, Setting, and Participants: This blinded randomized clinical trial enrolled patients with stage B and C HFpEF from the University of Vermont Medical Center pacemaker clinic between June 2019 and November 2020. Analysis was modified intention to treat. Interventions: Participants were randomly assigned to personalized accelerated pacing or usual care and were followed up for 1 year. The personalized accelerated pacing heart rate was calculated using a resting heart rate algorithm based on height and modified by ejection fraction. Main Outcomes and Measures: The primary outcome was the serial change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score. Secondary end points were changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, pacemaker-detected physical activity, atrial fibrillation from baseline, and adverse clinical events. Results: Overall, 107 participants were randomly assigned to the personalized accelerated pacing (n = 50) or usual care (n = 57) groups. The median (IQR) age was 75 (69-81) years, and 48 (48%) were female. Over 1-year follow-up, the median (IQR) pacemaker-detected heart rate was 75 (75-80) bpm in the personalized accelerated pacing arm and 65 (63-68) bpm in usual care. MLHFQ scores improved in the personalized accelerated pacing group (median [IQR] baseline MLHFQ score, 26 [8-45]; at 1 month, 15 [2-25]; at 1 year, 9 [4-21]; P < .001) and worsened with usual care (median [IQR] baseline MLHFQ score, 19 [6-42]; at 1 month, 23 [5-39]; at 1 year, 27 [7-52]; P = .03). In addition, personalized accelerated pacing led to improved changes in NT-proBNP levels (mean [SD] decrease of 109 [498] pg/dL vs increase of 128 [537] pg/dL with usual care; P = .02), activity levels (mean [SD], +47 [67] minutes per day vs -22 [35] minutes per day with usual care; P < .001), and device-detected atrial fibrillation (27% relative risk reduction compared with usual care; P = .04) over 1-year of follow-up. Adverse clinical events occurred in 4 patients in the personalized accelerated pacing group and 11 patients in usual care. Conclusions and Relevance: In this study, among patients with HFpEF and pacemakers, treatment with a moderately accelerated, personalized pacing rate was safe and improved quality of life, NT-proBNP levels, physical activity, and atrial fibrillation compared with the usual 60 bpm setting. Trial Registration: ClinicalTrials.gov Identifier: NCT04721314.

Reducing use of triple therapy after percutaneous coronary intervention: Results from a hospital-wide quality improvement initiative.

BACKGROUND: Trials have shown that for patients on oral anticoagulants (OAC), a short course of dual antiplatelet therapy (DAPT) with OAC reduces post-percutaneous coronary intervention (PCI) bleeding without increasing ischemic events. Adoption of this strategy has been variable. We evaluated the impact of an institutional quality improvement (QI) initiative to reduce the use of triple therapy (TT, OAC + DAPT) and improve discharge communication post-PCI. METHODS: A hospital-wide QI initiative was developed to minimize time on TT post-PCI. Interventions included institutional guidelines emphasizing discharge on OAC with a P2Y12 inhibitor or reducing TT duration to ≤30 days, changes to the computerized decision-support system, and an educational curriculum for house staff. PCI patients 18 months before and after the initiative (2017-2020) were reviewed along with a faculty survey assessing prescribing practices to evaluate the efficacy of the interventions. RESULTS: Among 2797 PCIs reviewed, 431 were included based on OAC at discharge: 24.9% female, 80.1% White, and the mean age was 74 years. The most common indications for OAC were atrial fibrillation (70.1%) and left ventricular dysfunction (11.4%). Mean duration of TT decreased (58.7-37.8 days, p = 0.02) and patients discharged on TT ≤ 30 days increased (24%-37%, p = 0.019) after intervention. Of surveyed faculty (n = 20), 75.0% reported familiarity with the guidelines and 57.9% reported using them to make therapy decisions. CONCLUSIONS: Following the implementation of a QI initiative, fewer patients were discharged on TT and shorter durations of TT were used. Similar initiatives should be considered at institutions with the prevalent use of TT post-PCI.

Late-Onset Leber's Hereditary Optic Neuropathy with Concurrent Retinal Detachment and Retrobulbar Visual Pathway Involvement.

We report a case of late-onset Leber's hereditary optic neuropathy (LHON) with concurrent retinal detachment, mild retinal pigment epithelial changes, cataract and hyperintensity on fluid-attenuated inversion recovery magnetic resonance imaging affecting the entire retrobulbar visual pathway. We also documented that progression of the visual field defect correlated with retinal nerve fibre layer and ganglion cell layer-inner plexiform layer changes on optical coherence tomography. Our case provides further understanding of LHON as a disorder of the entire pre-geniculate pathways and also highlights that detailed history taking in addition to recognition of typical sequential optic disc appearance and visual field characteristics at different stages of LHON remain critical even in this era of modern imaging, autoimmune biomarkers and genetic testing.

Basilar artery stroke in Crohn's disease treated with endovascular thromboembolectomy.

We describe a girl in middle childhood with newly diagnosed Crohn's disease, who presented with seizures and altered mental status. MRI showed an abnormal vascular signal at the basilar artery, but no evidence of acute ischaemia. Her weakness worsened over the next 8 hours to dense quadriplegia. CT angiography of the brain, approximately 24 hours after the initial onset of symptoms, identified an acute basilar artery occlusion with infarction. She received endovascular thromboembolectomy emergently. She showed significant improvement over 8-month period from quadriplegia to walking unassisted. This case highlights the importance of recognising stroke in patients with inflammatory bowel disease and the need for emergent radiological assessment and potential intervention.

Personalized pacing for diastolic dysfunction and heart failure with preserved ejection fraction: Design and rationale for the myPACE randomized controlled trial.

BACKGROUND: Patients with pacemakers and heart failure with preserved ejection fraction (HFpEF) or isolated diastolic dysfunction (DD) may benefit from a higher backup heart rate (HR) setting compared with the standard setting of 60 bpm. OBJECTIVE: The purpose of this study was to assess the effects of a personalized backup HR setting (myPACE group) compared with 60 bpm (control group). METHODS: In this prospective, blinded, randomized controlled study, pacemaker patients with DD or HFpEF and atrial pacing with intrinsic ventricular conduction or conduction system or biventricular pacing are randomized to the myPACE group or control group for 1 year. The primary outcome is the change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores. Secondary endpoints include changes in N-terminal pro-brain natriuretic peptide levels, physical and emotional MLHFQ subscores, and pacemaker-detected atrial arrhythmia burden, patient activity levels, and thoracic impedance; hospitalization for heart failure, atrial fibrillation, cerebrovascular accident, or myocardial infarction; and loop diuretic or antiarrhythmic medication initiation or up-titration. A sample size of 118 subjects is expected to allow detection of a 5-point change in MLHFQ score in an intention-to-treat analysis and allow initial assessment of clinical outcomes and subgroup analyses. RESULTS: Enrollment began in July 2019. As of November 2020, 107 subjects have been enrolled. It is projected that the 1-year follow-up will be completed by December 2021. CONCLUSION: Atrial pacing with intrinsic ventricular conduction or advanced ventricular pacing at a higher, personalized backup HR may be a therapeutic target for patients with isolated DD or HFpEF. The myPACE trial is designed to test this hypothesis.

Clinical impact of Bachmann's bundle pacing defined by electrocardiographic criteria on atrial arrhythmia outcomes.

AIMS: Evaluate whether Bachmann's bundle pacing (BBp) defined by electrocardiographic (ECG) criteria is associated with less atrial fibrillation/tachycardia (AF/AT) compared with anatomically defined right atrial septal pacing (RASp) and right atrial appendage pacing (RAAp). METHODS AND RESULTS: This is a retrospective study comparing BBp with non-specific RASp and RAAp on new incidence, burden, and recurrence of AF/AT. We included patients who underwent atrial lead placement between 2006 and 2019 and received > 20% atrial pacing. BBp was defined by paced P-wave morphology and fluoroscopic lead position. Compared with RASp (n = 107) and RAAp (n = 108), AF/AT burden was lower in the BBp (n = 134) group by repeated measures ANOVA (P < 0.001). Over 2-year follow-up, AF/AT burden increased in the RASp (P < 0.01) and RAAp (P < 0.01) groups but did not significantly change in the BBp group (P = 0.91). Atrial arrhythmia burden was lower in the BBp group than the RASp and RAAp groups at 12-15, 18-21, and 24-27 months (P < 0.05) after pacemaker placement. Risk of AF/AT recurrence was lower in BBp than RASp (HR 0.43; P < 0.01) and RAAp patients (HR 0.29, P < 0.01). Risk of de novo AF/AT was also lower in BBp than in RASp (OR 0.12; P < 0.01) and RAAp patients (OR 0.20, P < 0.01). CONCLUSION: Bachmann's bundle pacing defined using P-wave criteria was associated with decreased atrial arrhythmia burden, recurrence, and de novo incidence compared with right atrial septal pacing and right atrial appendage pacing.

Behaviors Interfering with Audiometry Associated with Eventual Diagnosis of Autism.

Children referred for audiology evaluation due to speech and language delays represent a neurodevelopmentally high-risk group. The audiology evaluation is a behaviorally-challenging encounter early in the diagnostic process. We assessed interfering behaviors (IB) that complicated completion of audiometry as predictors of autism spectrum disorder (ASD) diagnosis. This retrospective cohort study using the Military Health System electronic medical record included 296 children aged 18 to 71 months. Children who displayed IB had increased odds of receiving an ASD diagnosis compared to those who did not (OR = 5.6, 95% CI 2.6-12.1). Interfering behaviors had a high specificity (81%) and negative predictive value (94%) for ASD. The audiology evaluation may represent an opportunity early in the diagnostic process to stratify risk for ASD.

The effects of hypoxia on muscle deoxygenation and recruitment in the flexor digitorum superficialis during submaximal intermittent handgrip exercise.

BACKGROUND: Decreased oxygenation of muscle may be accentuated during exercise at high altitude. Monitoring the oxygen saturation of muscle (SmO2) during hand grip exercise using near infrared spectroscopy during acute exposure to hypoxia could provide a model for a test of muscle performance without the competing cardiovascular stresses that occur during a cycle ergometer or treadmill test. The purpose of this study was to examine and compare acute exposure to normobaric hypoxia versus normoxia on deoxygenation and recruitment of the flexor digitorum superficialis (FDS) during submaximal intermittent handgrip exercise (HGE) in healthy adults. METHODS: Twenty subjects (11 M/9 F) performed HGE at 50% of maximum voluntary contraction, with a duty cycle of 2 s:1 s until task failure on two occasions one week apart, randomly assigned to normobaric hypoxia (FiO2 = 12%) or normoxia (FiO2 = 21%). Near-infrared spectroscopy monitored SmO2, oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) over the FDS. Surface electromyography derived root mean square and mean power frequency of the FDS. RESULTS: Hypoxic compared to normoxic HGE induced a lower FDS SmO2 (63.8 ± 2.2 vs. 69.0 ± 1.5, p = 0.001) and both protocols decreased FDS SmO2 from baseline to task failure. FDS mean power frequency was lower during hypoxic compared to normoxic HGE (64.0 ± 1.4 vs. 68.2 ± 2.0 Hz, p = 0.04) and both decreased mean power frequency from the first contractions to task failure (p = 0.000). Under both hypoxia and normoxia, HHb, tHb and root mean square increased from baseline to task failure whereas O2Hb decreased and then increased during HGE. Arterial oxygen saturation via pulse oximetry (SpO2) was lower during hypoxia compared to normoxia conditions (p = 0.000) and heart rate and diastolic blood pressure only demonstrated small increases. Task durations and the tension-time index of HGE did not differ between normoxic and hypoxic trials. CONCLUSION: Hypoxic compared to normoxic HGE decreased SmO2 and induced lower mean power frequency in the FDS, during repetitive hand grip exercise however did not result in differences in task durations or tension-time indices. The fiber type composition of FDS, and high duty cycle and intensity may have contributed greater dependence on anaerobiosis.

Trauma-Informed Care in Pediatrics: A Developmental Perspective in Twelve Cases with Narratives.

INTRODUCTION: The dose-response relationship of adverse childhood experiences (ACEs) with chronic morbidities is recognized as prevalent. However, screening for ACEs and implementing trauma-informed care (TIC) have yet to become a standard of care in pediatrics. OBJECTIVES: To document impactful developmental experiences of implementing TIC and universal screening of ACEs in the pediatric setting, elucidate the relationship between ACEs and their common presentation of developmental and behavioral health problems in pediatric patients, and propose feasible system changes to promote evidence-based professional expertise. METHODS: During pediatric residency training, I implemented routine universal screening of pediatric patients using ACE questionnaires. Research-based trauma-informed practices, such as patient-centered communication regarding adverse health outcomes associated with prevalent ACEs, were used. Clinical vignettes describe 12 cases. RESULTS: Most patients and their families were receptive to counsel on recognizing, preventing, and mitigating the effects of toxic stress resulting from ACEs. Behavior in a patient, and sometimes a parent, was addressed from a developmentally sensitive lens of TIC, and appropriate therapeutic interventions were discussed. Addressing ACEs opened crucial conversations with some patients, which promoted efficacious, developmentally sensitive care. DISCUSSION: Implementing TIC in the pediatric setting, especially in training, is not only feasible but also vital to adequately understand the patient population. Equipped with clinical knowledge and experience in addressing ACEs, practitioners will more readily empower patients and their families to improve health outcomes. CONCLUSION: When pediatric practitioners discover, intervene, and address the adverse effects of ACEs, their care becomes more efficacious and evidence based.

Assessment of Cardiovascular Risk by the Combination of Clinical Risk Scores Plus Platelet Expression of FcγRIIa.

Platelet expression of FcγRIIa was quantified after myocardial infarction (MI) and we found that patients with high platelet FcγRIIa expression (>11,000/platelet) had a fourfold greater risk of subsequent MI, stroke, and death. This analysis of the original cohort of 197 patients was designed to determine whether platelet expression of FcγRIIa could be used in combination with clinical risk scores (GRACE [Global Registry of Acute Coronary Events] and DAPT [Dual Antiplatelet Therapy]) to refine cardiovascular risk assessment. Platelet expression of FcγRIIa quantified with the use of flow cytometry was broadly distributed in patients stratified into high and low risk groups based on clinical risk scores. In patients identified as high risk by the GRACE score, 62% had high platelet FcγRIIa expression. Similarly, in patients identified as high risk by DAPT, 55% had high platelet FcγRIIa expression. High platelet FcγRIIa expression discriminated high and low risk cohorts in patients with high cardiovascular risk defined by either the GRACE score (high platelet FcγRIIa 18.9% vs low platelet FcγRIIa 0%; odds ratio = 15.7, p = 0.06) or the DAPT score (high platelet FcγRIIa 15.4% vs low platelet FcγRIIa 3.7%; odds ratio = 5.6, p = 0.03) assessment. Platelet expression of FcγRIIa merits additional study to determine whether low platelet FcγRIIa expression can be used to guide early transition to aspirin monotherapy and high platelet FcγRIIa expression can be used to guide continuation of DAPT.

Variation in platelet expression of FcγRIIa after myocardial infarction.

FcγRIIa amplifies platelet activation and greater platelet expression of FcγRIIa identifies patients at greater risk of subsequent cardiovascular events. Thus, platelet expression of FcγRIIa may be useful to guide therapy. Because platelet function tests are impacted by preparative procedures and substantial intra-individual variability, we examined the impact of these factors on platelet expression of FcγRIIa in blood from healthy subjects and in patients after myocardial infarction (MI). Platelet expression of FcγRIIa was quantified with the use of flow cytometry. Blood was taken from healthy subjects and 114 patients after a MI in whom platelet expression of FcγRIIa was quantified before discharge and at 6 ± 1 months. Neither anticoagulants nor the antiplatelet agent cangrelor changed platelet expression of FcγRIIa. Intra-individual variation in platelet FcγRIIa expression was 8.5% ± 5% over the course of 1 month in healthy subjects. Platelet FcγRIIa expression was within 20% of the baseline value after 6 months in 71% of patients after MI. In summary, because FcγRIIa is a protein on the surface of platelets, assay conditions and antiplatelet agents do not change expression. Intra-individual variability in platelet expression of FcγRIIa is modest. Accordingly, platelet expression of FcγRIIa is a marker of increased platelet reactivity that can be reliably and repeatedly measured.Clinical Trial Registration: NCT02505217.

Successful rheolytic mechanical thrombectomy of cerebral venous thrombosis in a pediatric patient.

Thrombosis of the deep cerebral venous system is associated with a significant risk of morbidity and mortality in the pediatric population. Anticoagulation is the mainstay of current treatment of cerebral venous thrombosis (CVT). Systemic or local delivery of thrombolytics may be used in cases of inexorable progression of CVT and neurological compromise. Mechanical thrombectomy has been described in adult patients with CVT and may offer the added advantage of accelerated thrombolysis in the face of rapid clinical deterioration. In this report the authors describe the use of rheolytic mechanical thrombectomy in a pediatric patient with extensive dural sinus and deep CVT.

Initial clinical experience with a new self-expanding nitinol stent for the treatment of intracranial cerebral aneurysms: the Cordis Enterprise stent.

BACKGROUND AND PURPOSE: A new neurovascular microstent, the Cordis Enterprise stent, composed of nitinol, with a closed cell design, was specifically developed for the treatment of wide-necked intracranial cerebral aneurysms. The purpose of this study was to evaluate the safety, feasibility, and initial clinical results of using this device in patients. METHODS: In clinical evaluation, five patients ranging in age from 54 to 71 years were electively treated. The smallest aneurysm measured 3.3 x 2.9 mm, and the largest aneurysm measured 10.6 x 8.5 mm (neck and height measurements). RESULTS: All five cases (100%) were technically successful without complications. In each case, the stent was accurately placed in the desired location, immediately followed by coil embolization to the desired degree of occlusion with a satisfactory result. The poststent and coil-occlusion angiogram demonstrated excellent blood flow across the stent, with satisfactory positioning of the coils within the aneurysm in all cases (100%). No patient suffered any clinical or neurologic complications, and all were discharged 1-3 days postprocedure, in stable condition with no new neurologic deficits. CONCLUSION: In early clinical studies, the Cordis Enterprise stent performed well. The stent was able to be well visualized, deployed easily, could be repositioned if needed, and was accurately placed without technical difficulties. The closed cell design allowed all coils to be placed within the aneurysm and remain outside the flow of the parent artery. No periprocedural complications were encountered.