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.

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.

Interdisciplinary management of acute ischaemic stroke - current evidence on training requirements for endovascular stroke treatment. Position Paper from the ESC Council on Stroke and the European Association for Percutaneous Cardiovascular Interventions with the support of the European Board of Neurointervention: A step forward.

Stroke, a vascular disease of the brain, is the #1 cause of disability and a major cause of death worldwide. Stroke has a major negative impact on the life of stroke-affected individuals, their families and the society. A significant proportion of stroke victims indicate that would have preferred death over their after-stroke quality of life. Mechanical thrombectomy (MT), opening the occluded artery using mechanical aspiration or a thrombus-entrapment device, is a guideline-mandated (class I, level of evidence A) treatment modality in patients with large vessel occlusion stroke. MT clinical benefit magnitude indicates that a universal access to this treatment strategy should be the standard of care. Today there is a substantial geographic variation in MT deliverability, with large-scale disparities in MT implementation. In many countries effective access to MT remains severely limited. In addition, many of the MT-treated patients are treated too late for a good functional outcome because of logistic delays that include transportations to remotely located, scarce, comprehensive stroke centres. Position Paper from the European Society of Cardiology Council on Stroke and European Association for Percutaneous Cardiovascular Interventions on interdisciplinary management of acute ischaemic stroke, developed with the support of the European Board of Neurointervention fills an important gap in systematically enabling interventional cardiologists to support stroke intervention in the geographic areas of unmet needs in particular. We review strengths and weaknesses of the document, and suggest directions for the next steps that are swiftly needed to deliver MT to stroke patients more effectively.

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.

High Tolerability of Pitavastatin Therapy: A Case Report of Comparison with other Statins.

INTRODUCTION: Myopathy is possibly the most clinically relevant statin-induced side effect. CASE PRESENTATION: We report a case of a 63-year-old healthy male with mixed dyslipidemia. He developed bilateral myalgia of the forearms with fluvastatin 40 mg/day, pravastatin 20 mg/day, and combination of atorvastatin 10 mg and ezetimibe 10 mg/day. The only hypolipidemic treatment that was tolerable was the combination of pitavastatin 1 mg and ezetimibe 10 mg/day. DISCUSSION: Pitavastatin demonstrated less potential for the development of myalgia compared to the so far considered most tolerable statins (i.e., fluvastatin and pravastatin). All the tested statins were used at the lowest approved dose for clinical use. CONCLUSION: The combination of pitavastatin 1 mg and ezetimibe appears to be a promising treatment choice for individuals who are intolerant to statin therapy due to muscle complaints.

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.).

Update on new stents and protection devices for carotid artery stenting: what we know, what we learnt recently and what we need to know.

Carotid artery stenting (CAS) is considered an alternative option to carotid endarterectomy (CEA) for significant carotid stenosis, in both symptomatic and asymptomatic patients. Comparing to CEA, CAS offers significant advantages. The most important arise from the minimally invasive nature of the procedure, which reduces the surgical complications and adds significant comfort to the patient, without compromising the efficacy. Nowadays, CAS can achieve acute and long-term outcome results comparable to CEA, maintaining low rates of periprocedural embolic events. Evolution of the stent design and routine application of protection devices, played an important role to CAS performance. In this review, we aim to present all available new data on stent design and protection devices while we pose a set of unanswered questions that need to be addressed in the future.

Acute myocardial infarction in a young bodybuilder taking anabolic androgenic steroids: A case report and critical review of the literature.

We describe a case report of a 30-year-old bodybuilder suffering acute myocardial infarction (AMI). He had been taking stanozolol and testosterone for two months. The coronary angiogram showed high thrombotic burden in the left anterior descending artery without underlying atherosclerosis. Few case reports of AMI in athletes taking anabolic androgenic steroids (AASs) have been reported so far. AAS-related AMI is possibly underreported in the medical literature due to the desire of the affected individuals to hide AAS use. Physicians should always consider the possibility of AAS abuse in the context of a young athlete suffering AMI. AASs can predispose to AMI through the acceleration of coronary atherosclerosis. Additionally, thrombosis without underlying atherosclerosis or vasospasm is highly possible to cause AMI in AAS users. Complications after AMI may be more frequent in AAS users.

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation.

BACKGROUND: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. METHODS: A literature search based on PubMed listings was performed using "Omega-3 fatty acids" and "atrial fibrilation" as key search terms. RESULTS: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. CONCLUSIONS: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions.

Fast virtual functional assessment of intermediate coronary lesions using routine angiographic data and blood flow simulation in humans: comparison with pressure wire - fractional flow reserve.

AIMS: To develop a simplified approach of virtual functional assessment of coronary stenosis from routine angiographic data and test it against fractional flow reserve using a pressure wire (wire-FFR). METHODS AND RESULTS: Three-dimensional quantitative coronary angiography (3D-QCA) was performed in 139 vessels (120 patients) with intermediate lesions assessed by wire-FFR (reference standard: ≤0.80). The 3D-QCA models were processed with computational fluid dynamics (CFD) to calculate the lesion-specific pressure gradient (ΔP) and construct the ΔP-flow curve, from which the virtual functional assessment index (vFAI) was derived. The discriminatory power of vFAI for ischaemia- producing lesions was high (area under the receiver operator characteristic curve [AUC]: 92% [95% CI: 86-96%]). Diagnostic accuracy, sensitivity and specificity for the optimal vFAI cut-point (≤0.82) were 88%, 90% and 86%, respectively. Virtual-FAI demonstrated superior discrimination against 3D-QCA-derived % area stenosis (AUC: 78% [95% CI: 70- 84%]; p<0.0001 compared to vFAI). There was a close correlation (r=0.78, p<0.0001) and agreement of vFAI compared to wire-FFR (mean difference: -0.0039±0.085, p=0.59). CONCLUSIONS: We developed a fast and simple CFD-powered virtual haemodynamic assessment model using only routine angiography and without requiring any invasive physiology measurements/hyperaemia induction. Virtual-FAI showed a high diagnostic performance and incremental value to QCA for predicting wire-FFR; this "less invasive" approach could have important implications for patient management and cost.

Confronting the residual cardiovascular risk beyond statins: the role of fibrates, omega-3 fatty acids, or niacin, in diabetic patients.

Diabetics are regarded a special category of patients known to experience higher rates of cardiovascular complications as compared to the non-diabetic ones. Despite substantial efforts to minimize these risks, with aggressive antiplatelet and lipid lowering therapy, some of the diabetic patients still have a considerable residual risk for cardiovascular adverse events. Important preclinical data with potent lipid-lowering agents, like fibrates, omega-3-fatty acids, and niacin, have shown that they can provide sufficient help in reducing rates of cardiovascular events. In the present review, we are aim to explain their basic mechanisms of action, to present all the available clinical data regarding the efficacy of those agents, and to identify specific diabetic patients' subsets, in whom supplementary therapy with those agents could provide substantial benefit in terms of clinical outcome and not only lipid profile improvement.

Combined intravenous treatment with ascorbic acid and desferrioxamine to reduce myocardial reperfusion injury in an experimental model resembling the clinical setting of primary PCI.

INTRODUCTION: During reperfusion of ischemic myocardium, oxygen-derived free radicals are produced and can cause deleterious effects, known as reperfusion injury. We aimed to determine if a combination of the antioxidant ascorbic acid and an iron-chelating agent desferrioxamine, which reduces the production of the hydroxyl radical via ferrum-catalyzed reactions, can exert a protective action against reperfusion injury. METHODS: Twenty-two young male farm pigs were anesthetized and subjected to 45 mins of ischemia and 3 and a half hours of reperfusion, in the left circumflex coronary artery territory, via the inflation and deflation of an angioplasty balloon. Animals were randomly assigned to receive either an intravenous infusion of 100 mg/ kg ascorbic acid and 60 mg/kg desferrioxamine (treatment group, TG) or an equal amount of normal saline (control group, CG). The I/R ratio, the ratio of the infarcted (necrotic) zone (I) to the myocardial area at risk (R) after 3 and a half hours of reperfusion, was calculated using the tetrazolium staining method. Left ventricular end diastolic pressure (LVEDP), number of episodes of ventricular arrhythmias, TIMI flow in the reperfused vessel, and left ventricular ejection fraction (LVEF) were evaluated within the first hour post reperfusion in order to assess further injury severity. RESULTS: There was no significant difference in the I/R between the TG (27.9 ± 2.2%) and the CG (32.9 ± 2.4%) (p=0.15). In both groups there was a significant reduction in LVEF (-11.6 ± 2.28% for TG and -12.0 ± 2.27% for CG, p<0.01 for both groups) and a significant increase in LVEDP (+3.2 ± 0.9 mmHg for TG and +4.6 ± 0.9 mmHg for CG, p<0.01 for both groups) compared to the baseline values. No significant difference was noted between groups (p=0.61 for LVEF and p=0.60 for LVEDP values, at one hour post reperfusion). In all other parameters measured, no significant difference was observed between the study groups. CONCLUSIONS: Intravenous treatment with a combination of the antioxidant ascorbic acid and the iron-chelating agent desferrioxamine does not provide significant protection against myocardial reperfusion injury.

Carotid artery stenting with proximal cerebral protection for patients with angiographic appearance of string sign.

OBJECTIVES: The aim of this study was to assess the safety and effectiveness of carotid artery stenting (CAS) with proximal cerebral protection in patients showing string sign at carotid angiography. BACKGROUND: Presence of string sign is a well-known factor for adverse events in patients with severe carotid artery disease undergoing CAS. METHODS: We used retrospective analysis of a cohort of patients who underwent carotid angiography with the intention to undergo carotid stenting and had angiographically documented string sign in the target lesion. RESULTS: From October 2006 to August 2007, 25 patients (21 men and 4 women, mean age 70.9 +/- 8.7 years) presented with string sign during carotid angiography. This was 6.0% of a total of 416 patients studied during the time of the study. Twenty patients (80.0%) were symptomatic, and 5 (20.0%) were asymptomatic. Carotid artery stenting was performed successively in all patients. Proximal cerebral protection was applied in all but 1 patient. The 30-day death/stroke rate was 0%. At 12-month follow-up neurological events did not occur; 1 patient developed a nonfatal myocardial infarction, and another patient died from noncardiac cause. The 12-month death/stroke rate was 4.0%. CONCLUSIONS: Carotid stenting under proximal cerebral protection seems to be a feasible and safe procedure to manage patients with severe carotid stenosis in presence of angiographic string sign. Further prospective trials are required to prove efficacy of CAS in larger study populations.

[Diagnosis and management of periprocedural complications of carotid artery stenting]. / Complicanze periprocedurali dello stenting carotideo: inquadramento diagnostico e terapeutico.

Despite the significant improvement in the materials and the techniques used during carotid artery stenting (CAS) as well as the increased operator experience during the last years, complications still occur. Up to now, neither a classification nor a common definition of the possible complications still exist. It would be crucial as a common platform for prompt recognition, evaluation, treatment and study of the complications during CAS procedures and to reduce the clinical sequelae. The aim of this article is to review the most frequent periprocedural complications, to analyze their incidence and etiology, and to suggest possible ways of management and prevention.