Biomarkers vs Machines: The Race to Predict Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a serious complication affecting up to 15% of hospitalized patients. Early diagnosis is critical to prevent irreversible kidney damage that could otherwise lead to significant morbidity and mortality. However, AKI is a clinically silent syndrome, and current detection primarily relies on measuring a rise in serum creatinine, an imperfect marker that can be slow to react to developing AKI. Over the past decade, new innovations have emerged in the form of biomarkers and artificial intelligence tools to aid in the early diagnosis and prediction of imminent AKI. CONTENT: This review summarizes and critically evaluates the latest developments in AKI detection and prediction by emerging biomarkers and artificial intelligence. Main guidelines and studies discussed herein include those evaluating clinical utilitiy of alternate filtration markers such as cystatin C and structural injury markers such as neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloprotease 2 with insulin-like growth factor binding protein 7 and machine learning algorithms for the detection and prediction of AKI in adult and pediatric populations. Recommendations for clinical practices considering the adoption of these new tools are also provided. SUMMARY: The race to detect AKI is heating up. Regulatory approval of select biomarkers for clinical use and the emergence of machine learning algorithms that can predict imminent AKI with high accuracy are all promising developments. But the race is far from being won. Future research focusing on clinical outcome studies that demonstrate the utility and validity of implementing these new tools into clinical practice is needed.

Effect of Low-Level Tragus Stimulation on Cardiac Metabolism in Heart Failure with Preserved Ejection Fraction: A Transcriptomics-Based Analysis.

Abnormal cardiac metabolism precedes and contributes to structural changes in heart failure. Low-level tragus stimulation (LLTS) can attenuate structural remodeling in heart failure with preserved ejection fraction (HFpEF). The role of LLTS on cardiac metabolism is not known. Dahl salt-sensitive rats of 7 weeks of age were randomized into three groups: low salt (0.3% NaCl) diet (control group; n = 6), high salt diet (8% NaCl) with either LLTS (active group; n = 8), or sham stimulation (sham group; n = 5). Both active and sham groups received the high salt diet for 10 weeks with active LLTS or sham stimulation (20 Hz, 2 mA, 0.2 ms) for 30 min daily for the last 4 weeks. At the endpoint, left ventricular tissue was used for RNA sequencing and transcriptomic analysis. The Ingenuity Pathway Analysis tool (IPA) was used to identify canonical metabolic pathways and upstream regulators. Principal component analysis demonstrated overlapping expression of important metabolic genes between the LLTS, and control groups compared to the sham group. Canonical metabolic pathway analysis showed downregulation of the oxidative phosphorylation (Z-score: -4.707, control vs. sham) in HFpEF and LLTS improved the oxidative phosphorylation (Z-score = -2.309, active vs. sham). HFpEF was associated with the abnormalities of metabolic upstream regulators, including PPARGC1α, insulin receptor signaling, PPARα, PPARδ, PPARGC1ß, the fatty acid transporter SLC27A2, and lysine-specific demethylase 5A (KDM5A). LLTS attenuated abnormal insulin receptor and KDM5A signaling. HFpEF is associated with abnormal cardiac metabolism. LLTS, by modulating the functioning of crucial upstream regulators, improves cardiac metabolism and mitochondrial oxidative phosphorylation.

Safety and efficacy of colchicine for the prevention of post-operative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Colchicine is an anti-inflammatory drug that may prevent post-operative atrial fibrillation (POAF). The effect of this drug has been inconsistently shown in previous clinical trials. We aimed to compare the efficacy and safety of colchicine vs. placebo to prevent POAF in patients undergoing cardiac surgery. METHODS AND RESULTS: A systematic search of EMBASE, MEDLINE, SCOPUS, ClinicalTrials.gov, and the Cochrane Library for randomized controlled trials (RCTs) was conducted from inception till April 2023. The primary outcome was the incidence of POAF after any cardiac surgery. The secondary outcome was the rate of drug discontinuation due to adverse events and adverse gastrointestinal events. Risk ratios (RR) were reported using the Mantel Haenszel method. A total of eight RCTs comprising 1885 patients were included. There was a statistically significant lower risk of developing POAF with colchicine vs. placebo (RR: 0.70; 95% CI: 0.59-0.82; P < 0.01, I2 = 0%), and this effect persisted across different subgroups. There was a significantly higher risk of adverse gastrointestinal events (RR: 2.20; 95% CI: 1.38-3.51; P < 0.01, I2 = 55%) with no difference in the risk of drug discontinuation in patients receiving colchicine vs. placebo (RR: 1.33; 95% CI: 0.93-1.89; P = 0.11, I2 = 0%). CONCLUSION: This meta-analysis of eight RCTs shows that colchicine is effective at preventing POAF, with a significantly higher risk of adverse gastrointestinal events but no difference in the rate of drug discontinuation. Future studies are required to define the optimal duration and dose of colchicine for the prevention of POAF.

Recognition and management of hemolysis following transcatheter aortic valve replacement in a patient with chronic kidney disease.

A 79-year-old female with chronic kidney disease (CKD) and transthoracic aortic valve replacement presented with exertional dyspnea and was found to have hemolysis due to moderate paravalvular leak. Balloon dilatation resolved symptoms and anemia. Detecting hemolysis related to paravalvular leak is challenging due to CKD, possibly leading to bone marrow suppression.

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial.

BACKGROUND: Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS). OBJECTIVES: In this study the authors conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of tVNS on POTS over a 2-month period relative to sham stimulation. METHODS: tVNS (20 Hz, 1 mA below discomfort threshold) was delivered using an ear clip attached to either the tragus (active; n = 12) or the ear lobe (sham; n = 14) for 1 hour daily over a 2-month period. Postural tachycardia was assessed during the baseline and 2-month visit. Heart rate variability based on 5-minute electrocardiogram, serum cytokines, and antiautonomic autoantibodies were measured at the respective time points. RESULTS: Mean age was 34 ± 11 years (100% female; 81% Caucasian). Adherence to daily stimulation was 83% in the active arm and 86% in the sham arm (P > 0.05). Postural tachycardia was significantly less in the active arm compared with the sham arm at 2 months (mean postural increase in heart rate 17.6 ± 9.9 beats/min vs 31.7 ± 14.4 beats/min; P = 0.01). Antiadrenergic autoantibodies and inflammatory cytokines were lower in the active arm compared with the sham arm at 2 months (P < 0.05). Heart rate variability was better in the active arm. No device-related side effects were observed. CONCLUSIONS: Our results support the emerging paradigm of noninvasive neuromodulation to treat POTS. Mechanistically, this effect appears to be related to reduction of antiautonomic autoantibodies and inflammatory cytokines, and improvement in autonomic tone. Further studies are warranted. (Autoimmune Basis for Postural Tachycardia Syndrome; NCT05043051).

Sex differences in atrial fibrillation ablation outcomes in patients with heart failure.

BACKGROUND: There is a lack of data on the impact of sex on the outcomes of patients with heart failure (HF) undergoing atrial fibrillation (AF) ablation. We aimed to analyze the association of sex with outcomes of atrial fibrillation ablation in patients with heart failure. METHODS: The National Readmissions Database (NRD) was analyzed from 2016 to 2019 to identify patients ≥ 18 years old with heart failure (HF) undergoing AF ablation. The outcomes of interest included peri-procedural complications, in-hospital mortality, resource utilization, and unplanned 1-year readmissions. The final cohort was divided into patients with HFrEF and HFpEF and outcomes were compared between males and females in both cohorts. RESULTS: A total of 23,277 patients with HF underwent AF ablation between 2016 and 2019, of which 14,480 had HFrEF and 8,797 had HFpEF. Among patients with HFrEF, 61.6% were males and 38.4% were females whereas, among patients with HFpEF, 35.4% were males and 64.6% were females. On a multivariable-adjusted analysis, in patients with HFrEF, there was no difference in the odds of in-hospital mortality, peri-procedural complications, or 1-year HF-related/AF-related/all-cause readmissions between males and females. In patients with HFpEF, females had a higher risk 1-year HF-related readmissions (adjusted hazards ratio: 1.46; 95% CI: 1.13-1.87; p = 0.01), without any difference in the 1-year AF-related/all-cause readmissions, in-hospital mortality, or peri-procedural complications. CONCLUSION: Our results show that females with HFrEF undergoing AF ablation have similar outcomes whereas females with HFpEF have higher 1-year HF readmissions with no difference in the other outcomes, compared to males.

Atrial Myopathy and Ischemic Stroke in Heart Failure With Preserved Ejection Fraction.

Recent studies suggested an association between atrial myopathy and stroke independent of atrial fibrillation (AF). We examined the hypothesis that atrial myopathy may be associated with ischemic stroke in patients with heart failure with preserved ejection fraction. This is an exploratory, post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Patients with sinus rhythm documented at baseline electrocardiogram and without known AF were included in this analysis. Atrial myopathy was defined by echocardiographic evidence of left atrial (LA) enlargement (LA diameter >46 mm or LA volume index >36 ml/m2) or elevated natriuretic peptides (brain natriuretic peptide >100 pg/ml or N-terminal Pro-B-type natriuretic peptide >400 pg/ml). We used Cox regression to investigate the effect of atrial myopathy on incident ischemic stroke over the study period. In 3,445 patients in the TOPCAT trial, 2,225 (mean age 67.5 ± 4.9 years; female 54.8%) had normal sinus rhythm at baseline and no history of AF. Atrial myopathy was present in 756 patients (34.0%). During a median follow-up of 2 years, 56 patients (2.5%) developed ischemic stroke, including 25 with atrial myopathy. Atrial myopathy was associated with increased risk of stroke (hazard ratio = 1.74, 95% confidence interval 1.01 to 2.98, p = 0.04) in multivariate analysis. Diabetes mellitus (hazard ratio = 2.02, 95% confidence interval 1.19 to 3.43 p = 0.01) was the only other independent predictor of stroke. In patients with heart failure with preserved ejection fraction, atrial myopathy increases the risk of ischemic stroke, in the absence of AF. Further investigations are needed to better characterize this association and implement stroke prevention strategies.

Autonomic Nervous System and Cardiac Metabolism: Links Between Autonomic and Metabolic Remodeling in Atrial Fibrillation.

Simultaneous activation of the sympathetic and parasympathetic nervous systems is crucial for the initiation of paroxysmal atrial fibrillation (AF). However, unbalanced activation of the sympathetic system is characteristic of autonomic remodeling in long-standing persistent AF. Moreover, the adrenergic activation-induced metabolic derangements provide a milieu for acute AF and promote the transition from the paroxysmal to the persistent phase of AF. On the other hand, cholinergic activation ameliorates the maladaptive metabolic remodeling in the face of metabolic challenges. Selective inhibition of the sympathetic system and restoration of the balance of the cholinergic system by neuromodulation is emerging as a novel nonpharmacologic strategy for managing AF. This review explores the link between cardiac autonomic and metabolic remodeling and the potential roles of different autonomic modulation strategies on atrial metabolic aberrations in AF.

Candida endocarditis: Update on management considerations.

The rise in incidence rates of invasive candidiasis warrants an increase in attention and efforts toward preventing and treating this virulent infection. Cardiac involvement is one of the most feared sequelae and has a poor prognosis. Despite the introduction of several novel antifungal agents over the past quarter century, complications and mortality rates due to Candida endocarditis have remained high. Although fungal endocarditis has a mechanism similar to bacterial endocarditis, no specific diagnostic criteria or algorithm exists to help guide its management. Furthermore, recent data has questioned the current guidelines recommending a combined approach of antifungal agents with surgical valve or indwelling prostheses removal. With the emergence of multidrug-resistant Candida auris, a focus on improved prophylactic measures and management strategies is necessary.

Non-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a chronic debilitating condition of orthostatic intolerance, predominantly affecting young females. Other than postural tachycardia, symptoms of POTS include a spectrum of non-cardiac, systemic and neuropsychiatric features. Despite the availability of widespread pharmacological and non-pharmacological therapeutic options, the management of POTS remains challenging. Exaggerated parasympathetic withdrawal and sympathetic overdrive during postural stress are principal mechanisms of postural tachycardia in POTS. Non-invasive, transcutaneous, vagus nerve stimulation (tVNS) is known to restore sympathovagal balance and is emerging as a novel therapeutic strategy in cardiovascular conditions including arrhythmias and heart failure. Furthermore, tVNS also exerts immunomodulatory and anti-inflammatory effects. This review explores the effects of tVNS on the pathophysiology of POTS and its potential as an alternative non-pharmacological option in this condition.

The impact of the clinical diagnosis on the vagal response and heart rate after ganglionated plexus ablation.

BACKGROUND: Ganglionated plexi (GP) ablation may be associated with improved syncope or arrhythmia-free survival arrhythmia patients with vasovagal syncope (VVS) and atrial fibrillation (AF), respectively. We aimed to compare the characteristics of vagal response (VR) and clarify the effect on heart rate after GP ablation based on clinical diagnosis. METHODS: A total of 83 consecutive patients undergoing GP ablation were divided following two groups: (1) GP ablation for VVS (VVS group, n = 43) and (2) GP ablation in addition to pulmonary vein isolation (AF group, n = 40). We examined VR characteristics during RF ablation and high frequency stimulation, respectively, in the VVS and AF groups. To evaluate immediate and long-term heart rate response, a standard 12-lead ECG was obtained at baseline at 24 h after ablation and at the last follow-up visit. RESULTS: In the VVS group, the superior and inferior left atrial GPs were the most common GP sites at which a VR was observed. No VR was seen during radiofrequency application in the superior and inferior right atrial GPs in the VVS group. On the contrary, VR was more prevalent in the right-sided GPs during high-frequency stimulation in the AF group. VR was observed during ablation in only one patient with AF. Although the heart rate increased significantly after ablation in both groups, the effect was more prominent and durable in the VVS group. CONCLUSIONS: The autonomic response during GP ablation is different in VVS compared to AF, suggesting that VVS and AF may represent distinct forms of autonomic hyperactivity.

Diabetes and depression in Lebanon and association with glycemic control: a cross-sectional study.

BACKGROUND: Diabetes mellitus is a chronic noncommunicable disease characterized by hyperglycemia and is associated with chronic complications affecting the overall quality of life. As of 2017, the prevalence of diabetes in Lebanon is estimated to be 14.6%. Depression is noted to be common among Lebanese citizens, present in around 17.3%. This study aims to investigate the prevalence of depression among the diabetic Lebanese citizens and to study its relationship with poor glycemic control and diabetes complications. METHODS: In total, 436 diabetic patients participated in this cross-sectional study. Patients with diabetes mellitus attending several private clinics and health care centers were asked to fill out a well-structured questionnaire developed by an expert. Depression was assessed using Beck Depression Inventory (BDI). The study collected demographic information about the participants including their lifestyles, their last reported glycosylated hemoglobin values, and their reported microvascular and macrovascular complications. Data were collected, entered, and analyzed on SPSS software version 23.1. A descriptive analysis is carried out by calculating the mean and standard deviation for continuous variables and number and percentage for categorical ones. Association between categorical variables is evaluated using a chi-squared test. A P-value of <0.05 is considered to be significant. RESULTS: Depression was prevalent among 28.8% of the patients with diabetes mellitus. The average age of participants was 64.08 years. In total, 280 (64.2%) of the participants were females and the average diabetes duration was 8.89 years. There was no significant relationship found between depression and glycemic control. By contrast, a significant association between retinopathy, nephropathy, and stroke and depression was found. CONCLUSION: Depression was found to be present among 28.8% of the patients with diabetes mellitus in Lebanon; however, no association was established between depression and glycemic control.