The impact of age on ablation outcomes in AF-mediated cardiomyopathy

Introduction

The absence of ventricular scar in patients with atrial fibrillation (AF) and systolic heart failure (HF) predicts left ventricular (LV) recovery following AF ablation. It is unknown whether age impacts the degree of LV recovery, reverse remodeling, or AF recurrence following catheter ablation (CA) among this population.

Objectives

To evaluate the impact of age on LV recovery and AF recurrence in a population with AF and systolic HF without fibrosis (termed AF-mediated cardiomyopathy) following CA.

Methods

Consecutive patients undergoing CA between 2013 and 2021 with LV ejection fraction (LVEF) < 45% and absence of cardiac magnetic resonance imaging (CMR) detected LV myocardial fibrosis were stratified by age (<65 vs. ≥65 years). Following CA, participants underwent remote rhythm monitoring for 12 months with repeat CMR for HF surveillance.

Results

The study population consisted of 70 patients (10% female, mean LVEF 33 ± 9%), stratified into younger (age < 65 years, 63%) and older (age ≥ 65 years, 37%) cohorts. Baseline comorbidities, LVEF (34 ± 9 vs. 33 ± 8 ≥65 years, p = .686), atrial and ventricular dimensions (left atrial volume index: 55 ± 21 vs. 56 ± 14 mL/m² age ≥ 65, p = .834; indexed left ventricular end-diastolic volume: 108 ± 40 vs. 104 ± 28 mL/m² age ≥ 65, p = .681), pharmacotherapy and ablation strategy (pulmonary vein isolation in all; posterior wall isolation in 27% vs. 19% age ≥ 65, p = .448; cavotricuspid isthmus in 9% vs. 11.5% age ≥ 65) were comparable (all p > .05) albeit a higher CHADS₂VASc score in the older cohort (2.7 ± 0.9 vs. 1.6 ± 0.6 age < 65, p < .001).   Freedom from AF was comparable (hazard ratio: 0.65, 95% confidence interval: 0.38–1.48, LogRank p = .283) as was AF burden [0% (interquartile range, IQR: 0.0–2.1) vs. age ≥ 65: [0% (IQR 0.0–1.7), p = .516], irrespective of age. There was a significant improvement in LV systolic function in both groups (ΔLVEF + 21 ± 14% vs. +21 ± 12% age ≥ 65, p = .913), with LV recovery in the vast majority (73% vs. 69%, respectively, p = .759) at 13 (IQR: 12–16) months. This was accompanied by comparable improvements in functional status (New York Heart Association class p = .851; 6-min walk distance 50 ± 61 vs. 93 ± 134 m in age ≥ 65, p = .066), biomarkers (ΔN-terminal-pro brain natriuretic peptide −139 ± 246 vs. −168 ± 181 age ≥ 65,p = .629) and HF symptoms (Short Form-36 survey Δphysical component summary p = .483/Δmental component summary, p = .841).

Conclusion

In patients undergoing CA for AF with systolic HF in the absence of ventricular scar, comparable improvements in ventricular function, symptoms, and freedom from AF are achieved irrespective of age.     

Targeting the bone marrow with activin A-overexpressing embryonic multipotent stromal cells specifically modifies B lymphopoiesis

In vitro and in vivo studies implicate a series of cytokines in regulation of lymphohematopoiesis. However, direct indications for a local role of most of these cytokines within the bone marrow is lacking. In the present study, we aimed to test the contribution of a specific cytokine, activin A, a member of the transforming growth factor-beta (TGF-beta) family, to lymphohematopoiesis in mouse bone marrow. We show that mouse embryonic fibroblasts (MEFs) are indistinguishable from multipotent stromal cells (MSCs). Such MEFs overexpressing activin A, supported in vitro myelopoiesis in long-term bone marrow cultures as effectively as control MEFs. In contrast, activin A-overexpressing MEFs interfered with the in vitro generation of B lineage cells in such cultures. Thus, excessive expression in vitro of activin A, by supportive stromal cells, causes preferential maturation of myeloid rather than lymphoid cells. Moreover, the activin A-overexpressing MEFs caused an increased incidence in vivo of relatively immature B lineage cells; upon transplantation through the spleen route, MEFs engrafted the bone marrow specifically. Activin A-overexpressing MEFs accumulated in the bone marrow compartment and slowed down the progression of B cell precursors along the differentiation pathway, while sparing the myeloid population. The assay system described in this paper provides a means to assess the contribution of a wide range of molecules to hematopoiesis without perturbing the constitution of other organs.     

Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2

Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious viruses. The mechanism resides in the inhibitory activity toward α-glucosidases that are involved in the early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19.     

A new interventional home care model for COVID management: Virtual Covid IP

AimAmidst COVID-19 pandemic, the health care delivery in India faces major challenges owing to the overwhelming hospitals, exhausted healthcare workers, and shortage of crucial medical supplies such as ventilators and oxygen. The study aims to propose a novel successful interventional home care model, the Virtual COVID In-Patient (VCIP) care for effective COVID management.MethodsThe Covid-19 positive patients enrolled in VCIP were chosen for the study. A 24/7 active multidisciplinary WhatsApp group was created for each patient, for remote monitoring of temperature, blood pressure, blood glucose, respiratory and pulse rate along with the symptoms. Advice on sleep and exercises were given along with the medication via video-audio consultations. Lab facility was provided at the doorstep. Training on various devices, medications including steroids, delivering subcutaneous injections etc were given via video platforms.ResultsAmong the 220 patients who availed the VCIP facility, only two were hospitalized, yielding a 99.5 % success rate in preventing hospitalizations and patients enrolled have been immensely satisfied with their experience.ConclusionsWith similar pandemics anticipated in near future, VCIP model may be considered for successful domiciliary treatment and overcoming the challenges.     

Etiology and outcomes of acute kidney disease in children: a cohort study

Clinical and Experimental Nephrology - There is paucity of information regarding the etiology and outcomes of Acute Kidney Disease (AKD) in children. The objectives of this cohort study were to...     

Trajectories of quality of life recovery and symptom burden after autologous hematopoietic cell transplantation in multiple myeloma

Early autologous hematopoietic cell transplantation (AHCT) with post-transplant maintenance therapy is standard of care in multiple myeloma (MM). While short-term quality of life (QOL) deterioration after AHCT is known, the long-term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT (N = 758), was conducted. FACT-BMT scores up to 4 years post-AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as ‘none/mild’ for scores 0–2 and ‘moderate/severe’ for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1-year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow-up was 6 years (range, 0.4–8.5 years). FACT-BMT scores improved between enrollment and 1-year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1-year, and 32% at 4 years post-AHCT. Predictors of low symptom burden at 1-year included low symptom burden at baseline: OR 2.7 (1.8–4.1), p < 0.0001; older age: OR 2.1 (1.3–3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4–3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT-BMT and subscale scores to population norms by 1-year post-transplant, though many patients continue to report moderate to severe severity in some symptoms at 1-year and beyond.