Development and validation of the Atri-Risk Conduction Index risk score to predict risk of atrial fibrillation after typical atrial flutter ablation.

BACKGROUND: Identification of patients at risk for atrial fibrillation (AF) after typical atrial flutter (tAFL) ablation is important to guide monitoring and treatment. OBJECTIVE: The purpose of this study was to create and validate a risk score to predict AF after tAFL ablation METHODS: We identified patients who underwent tAFL ablation with no AF history between 2017 and 2022 and randomly allocated to derivation and validation cohorts. We collected clinical variables and measured conduction parameters in sinus rhythm on an electrophysiology recording system (CardioLab, GE Healthcare). Univariate and multivariate logistic regressions (LogR) were used to evaluate association with AF development. RESULTS: A total of 242 consecutive patients (81% male; mean age 66 ± 11 years) were divided into derivation (n =142) and validation (n = 100) cohorts. Forty-two percent developed AF over median follow-up of 330 days. In multivariate LogR (derivation cohort), proximal to distal coronary sinus time (pCS-dCS) ≥70 ms (odds ratio [OR] 16.7; 95% confidence interval [CI] 5.6-49), pCS time ≥36 ms (OR 4.5; 95% CI 1.5-13), and CHADS2-VASc score ≥3 (OR 4.3; 95% CI 1.6-11.8) were independently associated with new AF during follow-up. The Atri-Risk Conduction Index (ARCI) score was created with 0 as minimal and 4 as high-risk using pCS-dCS ≥70 ms = 2 points; pCS ≥36 ms = 1 point; and CHADS2-VASc score ≥3 = 1 point. In the validation cohort, 0% of patients with ARCI score = 0 developed AF, whereas 89% of patients with ARCI score = 4 developed AF. CONCLUSION: We developed and validated a risk score using atrial conduction parameters and clinical risk factors to predict AF after tAFL ablation. It stratifies low-, moderate-, and high-risk patients and may be helpful in individualizing approaches to AF monitoring and anticoagulation.

Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation in the United States.

BACKGROUND: Among patients hospitalized for atrial fibrillation, the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown. METHODS: Using the Get With The Guidelines-Atrial Fibrillation registry, patients admitted from January 1, 2014, to March 31, 2020, and discharged on DOACs were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing (defined as underdosing or overdosing) were identified using logistic regression. Median odds ratio (OR) and time-series analyses were used to assess hospital-level variation and temporal trends, respectively. RESULTS: Of 22 470 patients (70.1±12.1 years, 48.1% female, 82.5% White) prescribed a DOAC at discharge from hospitalization for atrial fibrillation (66% apixaban, 29% rivaroxaban, and 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19 953 (88.8%). The overall rate of off-label dosing was 11.2%. Patient-related factors associated with off-label dose included age (underdosing: OR, 1.06 per 1-year increase [95% CI, 1.06-1.07]; overdosing: OR, 1.07 per 1-year increase [95% CI, 1.06-1.09]), dialysis dependence (underdosing: OR, 5.50 [95% CI, 3.76-8.05]; overdosing: OR, 5.47 [95% CI, 2.74-10.88]), female sex (overdosing: OR, 0.79 [95% CI, 0.63-0.99]), and weight (overdosing: OR, 0.96 per 1-kg increase [95% CI, 0.95-1.00]). Across hospitals, the adjusted median OR for off-label DOAC dose was 1.45 (95% CI, 1.34-1.65; underdosing: OR, 1.52 [95% CI, 1.39-1.76]; overdosing: OR, 1.32 [95% CI, 1.20-1.84]), indicating significant hospital-level variation. Over the study period, recommended dosing significantly increased over time (81.9%-90.9%; P<0.0001 for trend) with a corresponding decline in underdosing (14.4%-6.6%; P<0.0001 for trend) and overdosing (3.8%-2.5%; P=0.001 for trend). CONCLUSIONS: Over 1 in 10 patients hospitalized for atrial fibrillation are discharged on an off-label DOAC dose with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.

Do Wearable Activity Trackers Increase Physical Activity Among Cardiac Rehabilitation Participants? A SYSTEMATIC REVIEW AND META-ANALYSIS.

PURPOSE: The objective of this study was to review randomized controlled trials (RCT), which included a wearable activity tracker in an intervention to promote physical activity among cardiac rehabilitation (CR) participants, and to conduct a meta-analysis for the outcomes of step counts and aerobic capacity (V˙o2max). METHODS: Eight databases were searched for RCTs that included an activity tracker, enrolled adults eligible for CR, and reported outcomes of step count or aerobic capacity. Mean differences were calculated for outcomes in the meta-analyses. RESULTS: Nineteen RCTs with 2429 participants were included in the systematic review and 10 RCTs with 891 participants were included in the meta-analysis. Meta-analysis of three RCTs using a pedometer or accelerometer demonstrated a significant increase in daily step count compared with controls (n = 211, 2587 steps/d [95% CI, 916-5257]; I2 = 74.6% and P = .002). Meta-analysis of three RCTs using a pedometer or accelerometer intervention demonstrated a significant increase in V˙o2max compared with controls (n = 260, 2.6 mL/min/kg [95% CI, 1.6-3.6]; I2 = 0.0% and P < .0001). Meta-analysis of four RCTs using a heart rate monitor demonstrated a significant increase in V˙o2max compared with controls (n = 420, 1.4 mL/min/kg [95% CI, 0.4-2.3]; I2 = 0.0% and P = .006). CONCLUSIONS: Use of activity trackers among CR participants was associated with significant increases in daily step count and aerobic capacity when compared with controls. However, study size was small and variability in intervention supports the need for larger trials to assess use of activity trackers in CR.

Impact of the influenza vaccine on COVID-19 infection rates and severity.

BACKGROUND: With a unique influenza season occurring in the midst of a pandemic, there is interest in assessing the role of the influenza vaccine in COVID-19 susceptibility and severity. METHODS: In this retrospective cohort study, patients receiving a laboratory test for COVID-19 were identified. The primary outcome was comparison of positive COVID-19 testing in those who received the influenza vaccine versus those who did not. Secondary end points in patients testing positive for COVID-19 included mortality, need for hospitalization, length of stay, need for intensive care, and mechanical ventilation. RESULTS: A total of 27,201 patients received laboratory testing for COVID-19. The odds of testing positive for COVID-19 was reduced in patients who received an influenza vaccine compared to those who did not (odds ratio 0.76, 95% CI 0.68-0.86; P < .001). Vaccinated patients testing positive for COVID-19 were less likely to require hospitalization (odds ratio, 0.58, 95% CI 0.46-0.73; P < .001), or mechanical ventilation (odds ratio, 0.45, 95% CI 0.27-0.78; P = .004) and had a shorter hospital length of stay (risk ratio, 0.76, 95% CI 0.65-0.89; P < .001). CONCLUSION: Influenza vaccination is associated with decreased positive COVID-19 testing and improved clinical outcomes and should be promoted to reduce the burden of COVID-19.

Impact of patient characteristics and perceived barriers on referral to exercise rehabilitation among patients with pulmonary hypertension in the United States.

Exercise rehabilitation is underutilized in patients with pulmonary arterial hypertension despite improving exercise capacity and quality of life. We sought to understand the association between (1) patient characteristics and (2) patient-perceived barriers and referral to exercise rehabilitation. We performed a cross-sectional survey of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension attending an International PAH meeting. Predictors of referral considered included gender, body mass index, subjective socioeconomic status, insurance type, age, and World Health Organization functional class and perceived barriers assessed using the Cardiac Rehabilitation Barriers Scale. Among 65 participants, those in the lowest subjective socioeconomic status tertile had reduced odds of referral compared to the highest tertile participants (odds ratio 0.22, 95% confidence interval: 0.05-0.98, p = 0.047). Several patient-perceived barriers were associated with reduced odds of referral. For every 1-unit increase in a reported barrier on a five-point Likert scale, odds of referral were reduced by 85% for my doctor did not feel it was necessary; 85% for prefer to take care of my health alone, not in a group; 78% many people with heart and lung problems don't go, and they are fine; and 78% for I didn't know about exercise therapy. The lack of perceived need subscale and overall barriers score were associated with a 92% and 77% reduced odds of referral, respectively. These data suggest the need to explore interventions to promote referral among low socioeconomic status patients and address perceived need for the therapy.

Higher admission rates and in-hospital mortality for acute type A aortic dissection during Influenza season: a single center experience.

Triggering events for acute aortic dissections are incompletely understood. We sought to investigate whether there is an association between admission for acute type A aortic dissection (ATAAD) to the University of Michigan Medical Center and the reported annual influenza activity by the Michigan Department of Health and Human Services. From 1996-2019 we had 758 patients admitted for ATAAD with 3.1 admissions per month during November-March and 2.5 admissions per month during April-October (p = 0.01). Influenza reporting data by the Michigan Department of Health and Human Services became available in 2009. ATAAD admissions for the period 2009-2019 (n = 455) were 4.8 cases/month during peak influenza months compared to 3.5 cases/month during non-peak influenza months (p = 0.001). ATAAD patients admitted during influenza season had increased in-hospital mortality (11.0% vs. 5.8%, p = 0.024) and increased 30-day mortality (9.7 vs. 5.4%, p = 0.048). The results point to higher admission rates for ATAAD during months with above average influenza rates. Future studies need to investigate whether influenza virus infection affects susceptibility for aortic dissection, and whether this risk can be attenuated with the annual influenza vaccine in this patient population.

Resting Oxygen Consumption and Heart Failure: Importance of Measurement for Determination of Cardiac Output With the Use of the Fick Principle.

BACKGROUND: Resting oxygen consumption (VO2) is often estimated and frequently used to guide therapeutic decisions in symptomatic heart failure (HF) patients. The relationship between resting VO2 and symptomatic HF and the accuracy of estimations of VO2 in this population are unknown. METHODS AND RESULTS: We performed a cross-sectional study of HF patients (n = 691) and healthy control subjects (n = 77). VO2 was measured with the use of a metabolic cart, and estimated VO2 was calculated with the use of the Dehmer, LaFarge, and Bergstra formulas and the thermodilution method. The measured and estimated VO2 were compared and the potential impact of estimations determined. In the multivariable model, resting VO2 decreased with increasing New York Heart Association (NYHA) functional class in a stepwise fashion (ß NYHA functional class IV vs control = -36 mL O2/min; P < .001). Estimations of VO2 with the use of derived equations diverged from measured values, particularly for patients with NYHA functional class IV limitations. The percentage difference of measured VO2 versus estimated VO2 was >25% in 39% (n = 271), 25% (n = 170), 82% (n = 566), and 39% (n = 271) of HF patients when using the Dehmer, LaFarge, Bergstra, and thermodilution-derived estimations of VO2 respectively. CONCLUSIONS: Resting VO2 decreases with increasing NYHA functional class and is lower than in control subjects. Using estimations of VO2 to calculate CO may introduce clinically important error.

Cardiosphere-Derived Cells and Ischemic Heart Failure.

After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications. However, multiple studies have shown that the heart is, in fact, not an end-stage organ and that there are endogenous mechanisms in place that have the potential to spark regeneration. Stem cell therapy has emerged as a potential tool to tap into and activate this endogenous framework. Particularly promising are stem cells derived from cardiac tissue itself, referred to as cardiosphere-derived cells (CDCs). CDCs can be extracted and isolated from the patient's myocardium and then administered by intramyocardial injection or intracoronary infusion. After early success in the animal model, multiple clinical trials have demonstrated the safety and efficacy of autologous CDC therapy in humans. Clinical trials with allogeneic CDCs showed early promising results and pose a potential "off-the-shelf" therapy for patients in the acute setting after a myocardial infarction. The mechanism responsible for CDC-induced cardiac regeneration seems to be a combination of triggering native cardiomyocyte proliferation and recruitment of endogenous progenitor cells, which most prominently occurs via paracrine effects. A further understanding of the mediators involved in paracrine signaling can help with the development of a stem cell-free therapy, with all the benefits and none of the associated complications.

Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.

Mitochondria are key players in aging and in the pathogenesis of age-related diseases. Recent mitochondrial transcriptome analyses revealed the existence of multiple small mRNAs transcribed from mitochondrial DNA (mtDNA). Humanin (HN), a peptide encoded in the mtDNA 16S ribosomal RNA region, is a neuroprotective factor. An in silico search revealed six additional peptides in the same region of mtDNA as humanin; we named these peptides small humanin-like peptides (SHLPs). We identified the functional roles for these peptides and the potential mechanisms of action. The SHLPs differed in their ability to regulate cell viability in vitro. We focused on SHLP2 and SHLP3 because they shared similar protective effects with HN. Specifically, they significantly reduced apoptosis and the generation of reactive oxygen species, and improved mitochondrial metabolism in vitro. SHLP2 and SHLP3 also enhanced 3T3-L1 pre-adipocyte differentiation. Systemic hyperinsulinemic-euglycemic clamp studies showed that intracerebrally infused SHLP2 increased glucose uptake and suppressed hepatic glucose production, suggesting that it functions as an insulin sensitizer both peripherally and centrally. Similar to HN, the levels of circulating SHLP2 were found to decrease with age. These results suggest that mitochondria play critical roles in metabolism and survival through the synthesis of mitochondrial peptides, and provide new insights into mitochondrial biology with relevance to aging and human biology.