Heart Rate Variability and Heart Failure with Reduced Ejection Fraction: A Systematic Review of Literature.

Introduction: Autonomic impairment is a hallmark of heart failure with reduced ejection fraction (HFrEF). While there have been studies on general values for each index of heart rate variability (HRV) analysis in HFrEF, a systematic review comprehensively examining representative values in HFrEF is lacking.

Methods: We searched PubMed, Embase, and Cochrane databases to extract studies reporting representative values of HRV metrics in HFrEF.

Heart rate variability metrics and myocardial recovery in heart failure with reduced ejection fraction.

Purpose: Autonomic dysregulation is observed in heart failure (HF) with reduced ejection fraction (HFrEF). Abnormal heart rate variability (HRV), a measure of such dysregulation, is associated with poor prognosis in HFrEF. It is unknown if novel HRV metrics normalize in the patients with recovered ejection fraction (HFrecEF) compared to persistent HFrEF.

Autonomic neuromodulation for cardiomyopathy associated with metabolic syndrome - Prevention of precursors for heart failure with preserved ejection fraction.

Metabolic syndrome (MetS) induces a systemic inflammatory state which can lead to cardiomyopathy, manifesting clinically as heart failure (HF) with preserved ejection fraction (HFpEF). MetS components are intricately linked to the pathophysiologic processes of myocardial remodeling. Increased sympathetic nervous system activity, which is noted as an upstream factor of MetS, has been linked to adverse myocardial structural changes.

Neuromodulation Therapies in Heart Failure: A State-of-the-Art Review.

Heart failure (HF) continues to impact the population globally with increasing prevalence. While the pathophysiology of HF is quite complex, the dysregulation of the autonomic nervous system, as evident in heightened sympathetic activity, serves as an attractive pathophysiological target for newer therapies and HF. The degree of neurohormonal activation has been found to correlate to the severity of symptoms, decline in functional capacity, and mortality.

Cardio-respiratory coupling and myocardial recovery in heart failure with reduced ejection fraction.

Introduction: The interaction between the cardiovascular and respiratory systems in healthy subjects is determined by the autonomic nervous system and reflected in respiratory sinus arrhythmia. Recently, another pattern of cardio-respiratory coupling (CRC) has been proposed linking synchronization of heart and respiratory system. However, CRC has not been studied precisely in heart failure (HF) with reduced ejection fraction (EF) (HFrEF) according to the myocardial recovery.

Blood Pressure Variability After Non-invasive Low-level Tragus Stimulation in Acute Heart Failure.

Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days.

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention.

Methods: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry.

Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy: A First-in-Human Randomized Pilot Study. Neuromodulation in Cancer Study (NCAN).

Objectives: Cardiotoxic chemotherapy is used to treat malignancies such as breast cancer and lymphoma. These treatments predispose patients to cardiotoxicity that can lead to cancer treatment-related cardiac dysfunction (CTRCD). The use of high doses of anthracyclines or in combination with human epidermal growth factor receptor 2 antagonists is associated with a progressively higher risk of CTRCD.

Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.

Purpose: Acute decompensated heart failure (ADHF) is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown whether neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level tragus stimulation on inflammation and oxidative stress in ADHF.

Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.

Purpose: Acute decompensated heart failure is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown if neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level Tragus stimulation on inflammation and oxidative stress in ADHF.

The neurometabolic axis: A novel therapeutic target in heart failure.

Abnormal cardiac metabolism or cardiac metabolic remodeling is reported before the onset of heart failure with reduced ejection fraction (HFrEF) and is known to trigger and maintain the mechanical dysfunction and electrical, and structural abnormalities of the ventricle. A dysregulated cardiac autonomic tone characterized by sympathetic overdrive with blunted parasympathetic activation is another pathophysiological hallmark of HF. Emerging evidence suggests a link between autonomic nervous system activity and cardiac metabolism.

Protein kinase A: A potential marker of sympathovagal imbalance in heart failure.

Mitigation of cardiac autonomic dysregulation by neuromodulation technologies is emerging as a new therapeutic modality of heart failure (HF). This recent progress has necessitated the identification of a biomarker for the quantification of sympathovagal balance, the potential target of 'neuromodulation' strategies. The currently available autonomic nervous system assessment parameters do not truly reflect the sympathovagal balance of the ventricle.

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.

Cerebral small vessel disease (CSVD) is the leading cause of vascular cognitive impairment and is associated with COVID-19. However, contributing factors that often accompany CSVD pathology in COVID-19 patients may influence the incidence of cerebrovascular complications. Thus, a mechanism linking COVID-19 and CSVD has yet to be uncovered and differentiated from age-related comorbidities (i.

The role of age-associated autonomic dysfunction in inflammation and endothelial dysfunction.

Aging of the cardiovascular regulatory function manifests as an imbalance between the sympathetic and parasympathetic (vagal) components of the autonomic nervous system (ANS). The most characteristic change is sympathetic overdrive, which is manifested by an increase in the muscle sympathetic nerve activity (MSNA) burst frequency with age. Age-related changes that occur in vagal nerve activity is less clear.

Meta-analysis Analyzing the Effect of Therapies on 6-Minute Walk Distance in Heart Failure With Reduced Ejection Fraction.

The 6-minute walk distance (6MWD) carries prognostic value in patients with heart failure with reduced ejection fraction (HFrEF). We performed this systematic review and meta-analysis to evaluate the effect of heart failure therapies on improvement in 6MWD. A systematic search of MEDLINE and Embase was conducted for randomized controlled trials measuring 6MWD at baseline and at follow-up in at least 50 patients with HFrEF across both arms.

Microvascular dysfunction and neurovascular uncoupling are exacerbated in peripheral artery disease, increasing the risk of cognitive decline in older adults.

Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC).

Impact of low-level electromagnetic fields on the inducibility of atrial fibrillation in the electrophysiology laboratory.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. Research suggests that autonomic nervous (ANS) system dysfunction contributes to AF pathophysiology. Animal studies have shown that low-level electromagnetic fields (LL-EMF) are potentially capable of AF suppression.

Effects of Low-Level Tragus Stimulation on Endothelial Function in Heart Failure With Reduced Ejection Fraction.

Background: Autonomic dysregulation in heart failure with reduced ejection fraction plays a major role in endothelial dysfunction. Low-level tragus stimulation (LLTS) is a novel, noninvasive method of autonomic modulation.

Methods And Results: We enrolled 50 patients with heart failure with reduced ejection fraction (left ventricular ejection fraction of ≤40%) in a randomized, double-blinded, crossover study.

Utilization of guideline-directed medical therapy in patients with de novo heart failure with reduced ejection fraction: A Veterans Affairs study.

Background: The utilization of guideline-directed medical therapy (GDMT) significantly reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Previous studies have documented the underutilization of GDMT in HFrEF. The present study aimed to determine reasons for underutilization and achievement of target doses of GDMT in patients with de novo diagnosis of HFrEF.

Left Atrial Size May Predict Blood Pressure Improvement After Ganglionated Plexi Ablation in Addition to Pulmonary Vein Isolation.

Background: Hypertension (HTN) and atrial fibrillation (AF) commonly co-exist. An improvement in control of HTN in a subset of patients undergoing AF ablation was previously demonstrated by our group. In the present study, we aimed to assess whether left atrial (LA) size based on transthoracic echocardiography may predict the patients who demonstratebetter HTN improvement after ganglionated plexus ablation (GPA) in addition to pulmonary vein isolation (PVI).

Non-invasive Low-level Tragus Stimulation in Cardiovascular Diseases.

Low-level tragus stimulation (LLTS) is a non-invasive approach of transcutaneous vagus nerve stimulation. LLTS has applications in diseases of multiple systems, including epilepsy, depression, headache and potentially several cardiovascular diseases. LLTS has shown promising results in suppressing AF, alleviating post-MI ventricular arrhythmias and ischaemia-reperfusion injury along with improving diastolic parameters in heart failure with preserved left ventricular ejection fraction (HFpEF).