Autonomic Function in Obese Children and Adolescents: Systematic Review and Meta-Analysis.

Background: Obesity is invariably accompanied by autonomic dysfunction, although data in pediatric populations are conflicting. Methods: We conducted a systematic review and meta-analysis of 12 studies (totaling 1102 participants) comparing obese and normal-weight subjects (5-18 years of age), defined as body mass index >95th or <85th percentile, respectively. Using a random-effects model, we report the standardized mean differences (SMD) of sympathetic and vagal indices of heart rate variability. Results: Autonomic dysfunction was present in the obesity group, based on the average SMD in the standard deviation of sinus intervals (at -0.5340), and on the ratio of low (LF)- to high (HF)-frequency spectra (at 0.5735). There was no difference in sympathetic activity, but the heterogeneity among the relevant studies weakens this result. SMD in HF (at 0.5876), in the root mean square of successive differences between intervals (at -0.6333), and in the number of times successive intervals exceeded 50 ms divided by the total number of intervals (at -0.5867) indicated lower vagal activity in the obesity group. Conclusions: Autonomic dysfunction is present in obese children and adolescents, attributed to lower vagal activity. Further studies are needed in various pediatric cohorts, placing emphasis on sympathetic activity.

Therapeutic inertia in rhythm control strategies in hospitalized patients with fibrillation: Insights from Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

BACKGROUND: Current guidelines recommend a rhythm control strategy in patients with symptomatic atrial fibrillation (AF) while catheter ablation has been shown to be a safer and more efficacious approach than antiarrhythmic medications. METHODS: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. In this sub-study, we included 276 cases who had a history of AF, particularly on the rhythm strategy, and catheter ablation procedures had been performed before the index admission. RESULTS: Among 276 AF patients (mean age: 76.4 ±â€¯11.5 years, 58 % male), 60.9 % (N = 168) had persistent AF and 39.1 % (N = 108) had paroxysmal AF. Heart failure was the main cause of admission in 54.3 % (N = 145) of the patients, while 14.1 % (N = 39) were admitted due to paroxysmal AF, 7.3 % (N = 20) due to bradyarrhythmic reasons, and 6.5 % (N = 18) suffered from acute coronary syndrome. Most importantly, heart failure with reduced ejection fraction was present in 76 (27 %) patients. Only 10 patients out of the total (3 %, mean age 59.7 years) had undergone AF ablation while electrical cardioversion had been attempted in 37 (13.4 %) patients. Interestingly, in this AF population with heart failure, 3.6 % (N = 10) had a defibrillator implanted (4 single-chamber), and only 1.5 % (N = 4) had a cardiac resynchronization therapy defibrillator (CRT-D). CONCLUSION: High prevalence of persistent AF was detected in hospitalized patients, with heart failure being the leading cause of admission and main co-morbidity. Rhythm control strategies are notably underused, along with CRT-D implantation in patients with AF and heart failure.

Autonomic Responses During Acute Anterior Versus Inferior Myocardial Infarction: A Systematic Review and Meta-Analysis.

Autonomic responses elicited by myocardial infarction vary depending on the site of injury, but accurate assessment using heart rate variability during the acute phase is limited. We systematically searched PubMed without language restrictions throughout July 2023. We reviewed studies reporting autonomic indices separately for anterior and inferior infarcts, followed by a meta-analysis of those reporting the standard deviation of the inter-beat interval between normal sinus beats during the initial 24 hours after the onset of symptoms. Six studies were included, comprising 341 patients (165 anterior, 176 inferior infarcts), all with satisfactory scores on the Newcastle-Ottawa quality scale. The estimated average of the standardized mean difference (based on the random-effects model) was -0.722 (95% confidence intervals: -0.943 to -0.501), which differed from zero (z=-6.416, p<0.0001). This finding indicates sympathetic and vagal dominance during acute anterior and inferior infarcts, respectively, with excessive responses likely contributing to early arrhythmogenesis. Despite the amelioration of autonomic dysfunction by revascularization, infarct location should be considered when commencing ß-adrenergic receptor blockade, especially after delayed procedures.

Endothelin Modulates Rhythm Disturbances and Autonomic Responses to Acute Emotional Stress in Rats.

The ubiquitous peptide endothelin is currently under investigation as a modulatory factor of autonomic responses to acute emotional stress. Baseline plasma levels of endothelin alter blood pressure responses, but it remains unclear whether autonomic activity and arrhythmogenesis (i.e., brady- or tachyarrhythmias) are affected. We recorded sympathetic and vagal indices (derived from heart rate variability analysis), rhythm disturbances, voluntary motion, and systolic blood pressure after acute emotional stress in conscious rats with implanted telemetry devices. Two strains were compared, namely wild-type and ETB-deficient rats, the latter displaying elevated plasma endothelin. No differences in heart rate or blood pressure were evident, but sympathetic responses were blunted in ETB-deficient rats, contrasting prompt activation in wild-type rats. Vagal withdrawal was observed in both strains at the onset of stress, but vagal activity was subsequently restored in ETB-deficient rats, accompanied by low voluntary motion during recovery. Reflecting such distinct autonomic patterns, frequent premature ventricular contractions were recorded in wild-type rats, as opposed to sinus pauses in ETB-deficient rats. Thus, chronically elevated plasma endothelin levels blunt autonomic responses to acute emotional stress, resulting in vagal dominance and bradyarrhythmias. Our study provides further insights into the pathophysiology of stress-induced tachyarrhythmias and syncope.

Renal Complications after Percutaneous Coronary Interventions on Concurrent Metformin Therapy: A Systematic Review with Meta-Analysis.

Objective: Metformin, commonly prescribed in diabetic patients, can cause lactic acidosis. Although generally rare, this side effect remains a source of concern in procedures requiring contrast media, due to the risk of contrast-induced nephropathy. Temporarily withdrawing metformin during the peri-procedural period is often practiced, but clinical decisions are difficult in emergency situations, such as acute coronary syndromes. In this systematic review with meta-analysis, we aimed to further investigate the safety of percutaneous coronary interventions in patients on concurrent metformin therapy.Design, Setting and Participants: We analyzed studies in patients undergoing (elective or emergency) percutaneous coronary interventions with or without concurrent metformin administration, reporting on the incidence of metformin-associated lactic acidosis and peri-procedural renal function.Methods: PubMed, ClinicalTrials.gov, Cochrane Library, and Scopus were systematically searched without language restrictions throughout August 2022. Randomized clinical trials and observational studies were assessed with the Revised Cochrane Collaboration Risk of Bias tool and the Newcastle-Ottawa quality scale, respectively. Data synthesis addressed the mean drop in estimated glomerular filtration rate (eGFR) and the incidence of contrast-induced nephropathy, in addition to lactic acidosis.Results: Nine studies were included, totaling 2235 patients (1076 continuing metformin during the peri-procedural period), mostly with eGFR above 30 mL/min/1.73m2 No cases of lactic acidosis were reported. The mean post-procedural drop in eGFR was 6.81mL/min/1.73m2 (95% confidence interval [CI]: 3.41 to 10.21) in the presence of metformin and 5.34 mL/min/1.73m2 (95% CI: 2.98 to 7.70) in its absence. The incidence of contrast-induced nephropathy was not affected by concurrent metformin, as shown by a (between-groups) standardized mean difference of 0.0007 (95% CI: -0.1007 to 0.1022).Conclusion: Concurrent metformin during percutaneous coronary interventions in patients with relatively preserved renal function is safe, without added risk of lactic acidosis or contrast-induced nephropathy. Thus, emergency revascularization in the context of acute coronary syndromes should not be deferred. More data from clinical trials in patients with severe renal disease are needed.

Endothelin System and Ischemia-Induced Ventricular Tachyarrhythmias.

Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurring prior to medical attendance remain significant, mandating in-depth understanding of the underlying mechanisms. Sympathetic activation has long been known to play a key role in the pathophysiology of ischemia-induced arrhythmias, but the regulating factors remain under investigation. Several lines of evidence implicate the endothelin system (a family of three isopeptides and two specific receptors) as an important modulator of sympathetic activation in the setting of acute coronary syndromes. Such interaction is present in the heart and in the adrenal medulla, whereas less is known on the effects of the endothelin system on the central autonomic network. This article summarizes the current state-of-the-art, placing emphasis on early-phase arrhythmogenesis, and highlights potential areas of future research.

Association of non-invasive electrocardiographic risk factors with left ventricular systolic function in post-myocardial infarction patients with mildly reduced or preserved ejection fraction: Insights from the PRESERVE-EF study.

BACKGROUND: Electrocardiographic non-invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post-myocardial infarction (post-MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE-EF trial. METHODS: We studied 575 post-MI ischemia-free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non-sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T-wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence. RESULTS: There was a statistically significant relationship between LPs (Chi-squared = 4.975; p < .05), nsVT (Chi-squared = 5.749, p < .05), PVCs (r= -.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02-3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18-5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%-49% versus the preserved LVEF: ≥50%. CONCLUSION: Late potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post-MI patients with mildly reduced or preserved LVEF.

Autonomic Responses during Labor: Potential Implications for Takotsubo Syndrome.

Takotsubo syndrome is a serious complication of labor. Although the pathophysiologic role of excessive sympathetic activation is established in this process, concurrent vagal responses have not been adequately described. Moreover, it remains unclear whether autonomic activity depends on the mode of delivery. Here, we explored the hypothesis that the different management of cesarean and vaginal delivery may elicit diverse responses affecting both autonomic arms. For this aim, continuous electrocardiographic recording was performed in 20 women during labor, and non-invasive indices of sympathetic and vagal activity were compared between the two modes of delivery. We report sympathetic prevalence during cesarean delivery, caused by marked vagal withdrawal, whereas autonomic activity was rather stable during vaginal delivery. These differences may be attributed to the effects of anesthesia during cesarean delivery, along with the protective effects of oxytocin administration during vaginal delivery. Our results provide further insights on autonomic responses during labor that may prove useful in the prevention of complications, such as takotsubo syndrome.

Sympathetic Activation and Arrhythmogenesis after Myocardial Infarction: Where Do We Stand?

Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of the left ventricle. Despite the widespread use of ß-adrenergic blockade and implantable defibrillators, morbidity and mortality from chronic-phase ventricular tachyarrhythmias remains high, calling for further investigation on the underlying pathophysiology. Histological and functional studies have demonstrated extensive alterations of sympathetic nerve endings at the peri-infarct area and flow-innervation mismatches that create a highly arrhythmogenic milieu. Such accumulated evidence, along with the previously well-documented autonomic dysfunction as an important contributing factor, has stirred intense research interest for pharmacologic and non-pharmacologic neuromodulation in post-infarction heart failure. In this regard, aldosterone inhibitors, sacubitril/valsartan and sodium-glucose cotransporter type 2 inhibitors have shown antiarrhythmic effects. Non-pharmacologic modalities, currently tested in pre-clinical and clinical trials, include transcutaneous vagal stimulation, stellate ganglion modulation and renal sympathetic denervation. In this review, we provide insights on the pathophysiology of ventricular arrhythmogenesis post-myocardial infarction, focusing on sympathetic activation.

Should Deferred Stenting Still Be Considered in ST-Elevation Myocardial Infarction with High Thrombus Burden?

Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) may demonstrate distal microvascular embolization of thrombotic materials. We retrospectively examined 20 cases displaying extensive thrombus in the infarct-related artery (IRA), treated either with a two-step procedure, with interim tirofiban infusion, or immediate stent implantation. Distal embolization tended to be more common in the latter strategy, but, overall, the outcome was comparable. Thus, a two-staged procedure may be considered in selected cases of primary PCI associated with high thrombus burden.

Access-site Complications of the Transradial Approach: Rare But Still There.

In the past decade, the Transradial Approach (TRA) has constantly gained ground among interventional cardiologists. TRA's anatomical advantages, in addition to patients' acceptance and financial benefits, due to rapid patient mobilization and shorter hospital stay, made it the default approach in most catheterization laboratories. Access-site complications of TRA are rare and usually of little clinical impact, thus, they are often overlooked and underdiagnosed. Radial Artery Occlusion (RAO) is the most common, followed by radial artery spasm, perforation, hemorrhagic complications, pseudoaneurysm, arterio-venous fistula, and even rarer complications, such as nerve injury, sterile granuloma, eversion endarterectomy or skin necrosis. Most of them are conservatively treated, but rarely, surgical treatment may be needed and late diagnosis may lead to life-threatening situations, such as hand ischemia or compartment syndrome and tissue loss. Additionally, some complications may eventually lead to TRA failure and switch to a different approach. On the other hand, it is the opinion of the authors that non-occlusive radial artery injury, commonly included in TRA's complications in the literature, should be regarded more as an anticipated functional and anatomical cascade, following radial artery puncture and sheath insertion.

Treatment of Mobile Right Heart Thrombi.

Right heart thrombi are detected in approximately 4% of patients with pulmonary embolism. The associated mortality is high, but the optimal strategy remains controversial. We report a case of a large mobile right heart thrombus, complicated by embolism of the right pulmonary artery, which was successfully treated with half-dose alteplase. We briefly review the literature and discuss the therapeutic options, focusing on the advantages of thrombolysis. LEARNING POINTS: Mobile right heart thrombi require rapid therapeutic choices between surgical thrombectomy and thrombolysis.Half-dose alteplase may be effective, even in the presence of an extensive thrombus burden.

Sympathetic and Vagal Responses Elicited by Acute Stress in Rats.

Introduction Acute emotional stress triggers autonomic responses that affect sympathovagal balance. However, the temporal pattern of changes in each autonomic arm during stress and recovery remains unclear. Therefore, we analyzed separately sympathetic and vagal activity, elicited by acute unpredictable stress in a rat model. Methods Continuous electrocardiographic recording was performed during (32 minutes) and after (two hours) successive use of restraint and air-jet stress in 10 rats, whereas five rats served as controls. Sympathetic and vagal indices were calculated non-invasively after heart rate variability analysis. Voluntary motion was quantified during recovery, as an index of continuing anxiety. Results The sympathetic nervous system index increased during stress and remained elevated during the initial stage of recovery. The parasympathetic nervous system index decreased immediately after the onset of stress and remained low throughout the observational period. During recovery, voluntary activity was more pronounced in the stress group than in the controls. Conclusion Successive restraint and air-jet stress in rats increased sympathetic activity and decreased vagal activity. These changes displayed only partial recovery post-stress and were accompanied by enhanced voluntary motion. Our findings may be important in the evaluation of the cardiac electrophysiologic implications of autonomic changes elicited by acute emotional stress.

The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design.

OBJECTIVE: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. METHODS: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group. RESULTS: Trial results will be disseminated through peer-reviewed publications and conference presentations. CONCLUSION: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).

Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction.

Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.

Optical Coherence Tomography Facilitating Early Withdrawal of Antiplatelet Agents in a High-Bleeding Risk Patient.

Optical coherence tomography (OCT) can guide percutaneous coronary interventions to optimize results, thus minimizing the risk of stent thrombosis. We present the case of a cancer patient, paroxysmal atrial fibrillation, and unstable angina who underwent OCT-guided complex percutaneous coronary intervention and who required early discontinuation of antiplatelet therapy because of major bleeding. (Level of Difficulty: Beginner.).

Endothelin receptors in the brain modulate autonomic responses and arrhythmogenesis during acute myocardial infarction in rats.

AIMS: Endothelin has been implicated in various processes in the brain, including the modulation of sympathetic responses. The present study examined the pathophysiologic role of brain endothelin-receptors in the setting of acute myocardial infarction, characterized by high incidence of ventricular tachyarrhythmias. MAIN METHODS: We investigated the effects of intracerebroventricular administration of antagonists of endothelin-receptors ETA, ETB, or both, during a 24 h-observation period post-coronary ligation in (n = 70) rats. Continuous recording was performed via implanted telemetry transmitters, followed by arrhythmia-analysis and calculation of autonomic indices derived from heart rate variability. The regional myocardial electrophysiologic properties were assessed by monophasic action potentials and multi-electrode recordings. KEY FINDINGS: Sympathetic-activity was decreased and vagal-activity was enhanced after intracerebroventricular ETA-receptor blockade, thus attenuating regional myocardial repolarization inhomogeneity. As a result, the incidence of ventricular tachyarrhythmias was markedly lower in this group. Such effects were also observed after intracerebroventricular blockade of ETB-, or both, ETA- and ETB-receptors, although to a lesser extent. SIGNIFICANCE: ETA-receptors in the brain modulate sympathetic and vagal responses and alter arrhythmogenesis during evolving myocardial necrosis in rats. These findings provide insights into arrhythmogenic mechanisms during acute myocardial infarction and call for further investigation on the role of endothelin in the central autonomic network.

CPVT: Arrhythmogenesis, Therapeutic Management, and Future Perspectives. A Brief Review of the Literature.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a primary electrical disease characterized by a normal resting electrocardiogram and induction of malignant arrhythmias during adrenergic stress leading to syncope or sudden cardiac death (SCD). CPVT is caused by mutations in the cardiac ryanodine receptor (RyR2) or in the sarcoplasmic reticulum protein calsequestrin 2 genes (CASQ2). The RyR2 mutations are responsible for the autosomal dominant form of CPVT, while CASQ2 mutations are rare and account for the recessive form. These mutations cause a substantial inballance in the homeostasis of intracellular calcium resulting in polymorphic ventricular tachycardia through triggered activity. Beta blockers were for years the cornerstone of therapy in these patients. Sodium channel blockers, especially flecainide, have an additive role in those not responding in beta blockade. Implantation of defibrillators needs a meticulous evaluation since inappropriate shocks may lead to electrical storm. Finally, cardiac sympathetic denervation might also be an alternative therapeutic option. Early identification and risk stratification is of major importance in patients with CPVT. The aim of the present review is to present the arrhythmogenic mechanisms of the disease, the current therapies applied and potential future perspectives.

Optimization of Ca2+ content in alginate hydrogel injected in myocardium.

The spontaneous uptake of Ca2+ -ions is a unique property of alginate hydrogels, which, along with their high biocompatibility, disintegration (approximately within 2 weeks), and morphological similarity to heart tissue, makes them attractive as scaffolding materials in therapies in infarct myocardium. To shed light on the aforementioned ability, thorough theoretical calculations were carried out with the density functional theory (DFT) method. The influence of Ca-content οn the molecular structure and the thermodynamic stability of the alginate hydrogel was determined; what is more, these results effectively interpreted the experimental findings, as well. This analysis suggests that in Ca-free or Ca-deficient alginates spontaneous Ca2+ cations uptake can occur from the biological environment and develop, via chelation reaction, a well-formed and thermodynamically stable hydrogel in situ inside the tissue. The highest degree of cross linking results in viscosity peak. Nevertheless, further increase of Ca-content in alginate structure beyond this peak results in products with poorer thermodynamic stability. Structural optimization DFT calculations revealed that the destabilization of the Ca-rich alginate hydrogels is attributed to changes of the alginate chain molecule, which are relaxation, weakening, and eventually total collapse of the bond between the units of the alginate chain. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 223-231, 2019.