Modulating Sympathetic Nervous System with the use of SGLT2 Inhibitors: Where There is Smoke, There is Fire?

Heart failure (HF) has become even more prevalent in recent years, as a result of improved diagnostics and an increase in the risk factors predisposing to its pathology. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) emerged as one of the key pharmacotherapy options for both reduced and preserved ejection fraction, providing cardio- and renoprotection and improving mortality and cardiovascular (CV) outcomes. The pleiotropism of SGLT2i has led to multiple efforts to understand their distinct pathophysiological interactions with various pathways, including microcirculation, endothelial dysfunction, and inflammation. More recently, the role of SGLT2i on the sympathetic nervous system (SNS) is starting to be recognized, especially as observations of retained or reduced heart rate (HR) despite volume contraction have been noted by investigators in the large clinical trials testing the safety and efficacy of these agents. Both preclinical and clinical studies have been performed, with conflicting results. Interestingly, in both settings, whilst there are indications of SNS modulation by SGLT2i, other studies contradict such findings, without showing, however, worsening of the autonomic homeostasis. Given the importance of neuromodulation in HF, in both pharmacological and interventional therapies, in this review, we aim to describe the role of SNS in CV disease, focusing on HF, analyse preclinical and clinical data regarding the efficacy of SGLT2i in modulating autonomic dysfunction by examining various markers of SNS activation, as well as provide the most plausible theoretical backgrounds on the mechanism of benefit of SNS from the inhibition of SGLT2 receptors.

Iatrogenic atrial septal defects in structural heart interventions: Opening the Pandora's box.

In the modern era of structural heart interventions, the total number of transseptal procedures is growing exponentially, thus increasing the rate and need for management of iatrogenic atrial septal defects (iASDs). To date, there are no official guidelines on the assessment and management of iASDs, due to inconclusive evidence on whether patients benefit more from the percutaneous closure of iASD than from conservative management and vigorous follow-up. Despite the abundance of observational studies on iASDs, there is still a lack of randomized studies. Evidence so far show that percutaneous closure is no superior over conservative treatment in patients with iASDs, however, it has been demonstrated that patients with spontaneous closure of iASDs experience less heart failure (HF) hospitalizations. On the other hand, researchers have investigated the beneficial nature of interatrial shunt therapy in patients with HFpEF and, more recently, with HFrEF, due to the presumed hemodynamic benefits. Herein, we provide an updated review of relevant literature, focusing on iASD persistence rates, predicting factors for their persistence, and clinical outcomes of iASD persistence, to summarize available evidence and discuss future directions in the field.

Transcatheter Structural Heart Disease Interventions and Concomitant Left Atrial Appendage Occlusion: A State of the Art Review.

Atrial fibrillation (AF) is the most common arrhythmia in patients with valvular heart disease, and it can be associated with adverse patient outcomes. However, the need for anticoagulation to counterbalance AF-associated stroke risk may further lead to suboptimal outcomes via increasing bleeding events, especially in high-risk individuals. Because the vast majority of thrombi occur in the left atrial appendage, left atrial appendage occlusion (LAAO) is an established procedure for preventing ischemic stroke in patients with AF, while limiting anticoagulation-related bleeding events. Thus, the concept of combining an index procedure for structural heart disease (SHD) with LAAO seems promising for preventing future stroke events. A combined procedure has been described in aortic stenosis (transcatheter aortic valve implantation + LAAO), mitral regurgitation (transcatheter edge-to-edge repair + LAAO), and atrial septal defects (patent foramen ovale/atrial septal defect + LAAO). Evidence shows that a combined procedure can be safely performed in a "1-stop shop" fashion, without increased rates of procedural adverse events, with the potential to limit bleeding risk and provide prophylaxis against stroke events. This review analyses indications and clinical evidence regarding the safety and efficacy of combined SHD+LAAO procedures, while also providing insights into gaps in knowledge and future directions for the evolution of this field.

Atrial Functional Mitral Regurgitation: From Diagnosis to Current Interventional Therapies.

Mitral regurgitation (MR) is one of the most common valvular pathologies worldwide, contributing to the morbidity and mortality of several cardiovascular pathologies, including heart failure (HF). Novel transcatheter treatment for MR has given the opportunity for a safe and feasible alternative, to surgery, in order to repair the valve and improve patient outcomes. However, after the results of early transcatheter edge-to-edge repair (TEER) trials, it has become evident that subcategorizing the mitral regurgitation etiology and the left ventricular function, in patients due to undergo TEER, is of the essence, in order to predict responsiveness to treatment and select the most appropriate patient phenotype. Thus, a novel MR phenotype, atrial functional MR (AFMR), has been recently recognized as a distinct pathophysiological entity, where the etiology of the regurgitation is secondary to annular dilatation, in a diseased left atrium, with preserved left ventricular function. Recent studies have evaluated and compared the outcomes of TEER in AFMR with ventricular functional MR (VFMR), with the results favoring the AFMR. In specific, TEER in this patient substrate has better echocardiographic and long-term outcomes. Thus, our review will provide a comprehensive pathogenesis and mechanistic overview of AFMR, insights into the echocardiographic approach of such patients and pre-procedural planning, discuss the most recent clinical trials and their implications for future treatment directions, as well as highlight future frontiers of research in the setting of TEER and transcatheter mitral valve replacement (TMVR) in AFMR patients.

Computed Tomography Angiography Identified High-Risk Coronary Plaques: From Diagnosis to Prognosis and Future Management.

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements in the field have allowed us to identity not only the presence of obstructive disease but also the characteristics of identified lesions. High-risk coronary atherosclerotic plaques are identified in CT angiographies via a number of specific characteristics and may provide prognostic and therapeutic implications, aiming to prevent future ischemic events via optimizing medical treatment or providing coronary interventions. In light of new evidence evaluating the safety and efficacy of intervening in high-risk plaques, even in non-flow-limiting disease, we aim to provide a comprehensive review of the diagnostic algorithms and implications of plaque vulnerability in CT angiography, identify any differences with invasive imaging, analyze prognostic factors and potential future therapeutic options in such patients, as well as discuss new frontiers, including intervening in non-flow-limiting stenoses and the role of CT angiography in patient stratification.

Optimal management of high bleeding risk patients undergoing percutaneous coronary interventions: Where do we stand?

Percutaneous coronary interventions (PCI) are the mainstay of treating obstructive coronary artery disease. However, procedural planning and individualization of the procedure is necessary for different patient phenotypes to optimize outcomes. Specifically, post-PCI pharmacotherapy with antiplatelets complicates the management of patients at high bleeding risk due to comorbidities, such as atrial fibrillation. Aiming to limit post-procedural adverse events and reduce the procedure-related bleeding risk, several novel technologies and hypotheses have been tested in clinical practice. Such frontiers include limiting the duration of dual antiplatelet therapy or even prescribing single regimens, using drug-coated balloons for performing the intervention and the effect of imaging-guided PCI in optimizing stent expansion. Furthermore, specific instruction in different patient phenotypes, such as atrial fibrillation and chronic kidney disease, are emerging, as despite both pathologies being considered at high bleeding risk, one size does not fit all. Thus, our review will provide all the recent updates on the field as well as algorithms and expert opinions on how to manage this, particularly common, phenotype of patient.

Patent Foramen Ovale Closure in Special Clinical Situations: More Questions Than Answers?

Patent foramen ovale (PFO) is a remnant of the foetal circulation resulting from incomplete occlusion of the septum primum and septum secundum. Although prevalent in about 25% of the population, it mainly remains asymptomatic. However, its clinical significance in situations such as cryptogenic stroke, migraine, and decompression illness (DCI) has been well described. Recent randomised clinical trials (RCTs) have demonstrated the efficacy of percutaneous PFO closure over pharmacological therapy alone for secondary stroke prevention in carefully selected patients. Notably, these trials have excluded older patients or those with concurrent thrombophilia. Furthermore, the role of closure in other clinical conditions associated with PFO, like decompression sickness (DCS) and migraines, remains under investigation. Our review aims to summarise the existing literature regarding epidemiology, pathophysiological mechanisms, optimal management, and closure indications for these special patient groups.

Transoesophageal echocardiography beyond the echo-laboratory. An expert consensus paper of the working group of echocardiography of the hellenic society of cardiology.

Transoesophageal echocardiography (TOE) is a well-established and valid imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for several specific diagnoses and recently a useful guide of an increasing number of catheter-based and surgical interventions. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Society of Cardiology to state the essential steps of the TOE exam performed beyond the echo lab: a) in the operating rooms intraoperatively during either transcatheter interventions, or cardiothoracic surgery and b) in the intensive care unit for critically ill patients' monitoring. This paper includes information and tips and tricks about the pre-procedural evaluation, the procedural echocardiographic guidance, and post-procedural evaluation of the result and potential complications.

Preoperative and postoperative administration of vitamin C in cardiac surgery patients - settings, dosages, duration, and clinical outcomes: a narrative review.

Vitamin C or ascorbic acid is a water-soluble vitamin capable of directly donating electrons to reactive oxygen species, attenuating electrical remodeling, and cardiac dysfunction in patients undergoing cardiac surgery (CS), considered one of the most effective defenses against free radicals in the blood, thus being one of the first antioxidants consumed during oxidative stress. The aim of this review is to assess the effects of perioperative administration of vitamin C in CS patients. A comprehensive literature search was conducted in order to identify prospective cohort studies and/or randomized controlled trials reporting on the perioperative effects of vitamin C among adult patients undergoing CS. Studies published between January 1980 to December 2022 were included in our search, resulting in a total of 31 articles that met all our inclusion criteria. There seems to be a beneficial effect of vitamin C supplementation in arrhythmias such as in postoperative atrial fibrillation, reduction of ICU length of stay, and hospital length of stay, reduction in postoperative ventilation time, in inotropic demand, and in postoperative fatigue. Vitamin C can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane, and to protect the myocardium postoperatively from ischemia/reperfusion injury, thus attenuating oxidative stress and inflammation. It represents a readily available and cost-effective strategy that could improve the outcome of patients undergoing CS, by reducing the risk of serious cardiovascular adverse events, both perioperatively and postoperatively.

Practical guidance and clinical applications of transoesophageal echocardiography. A position paper of the working group of echocardiography of the Hellenic Society of Cardiology.

Transoesophageal echocardiography (TOE) is a well-established imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for a wide spectrum cardiac and extra-cardiac diseases. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Cardiology Society to state the essential steps of the typical TOE exam performed in echo lab. This is an educational text, describing the minimal requirements and the preparation of a meticulous TOE examination. Most importantly, it gives practical instructions to obtain and optimize TOE views and analyses the implementation of a combined two-and multi-dimensional protocol for the imaging of the most common cardiac structures during a TOE. In the second part of the article a comprehensive review of the contemporary use of TOE in a wide spectrum of valvular and non-valvular cardiac diseases is provided, based on the current guidelines and the experience of the WG members.

Renal Congestion in Heart Failure: Insights in Novel Diagnostic Modalities.

Heart failure is increasingly prevalent and is estimated to increase its burden in the following years. A well-reported comorbidity of heart failure is renal dysfunction, where predominantly changes in the patient's volume status, tubular necrosis or other mechanical and neurohormonal mechanisms seem to drive this impairment. Currently, there are established biomarkers evaluating the patient's clinical status solely regarding the cardiovascular or renal system. However, as the coexistence of heart and renal failure is common and related to increased mortality and hospitalization for heart failure, it is of major importance to establish novel diagnostic techniques, which could identify patients with or at risk for cardiorenal syndrome and assist in selecting the appropriate management for these patients. Such techniques include biomarkers and imaging. In regards to biomarkers, several peptides and miRNAs indicative of renal or tubular dysfunction seem to properly identify patients with cardiorenal syndrome early on in the course of the disease, while changes in their serum levels can also be helpful in identifying response to diuretic treatment. Current and novel imaging techniques can also identify heart failure patients with early renal insufficiency and assess the volume status and the effect of treatment of each patient. Furthermore, by assessing the renal morphology, these techniques could also help identify those at risk of kidney impairment. This review aims to present all relevant clinical and trial data available in order to provide an up-to-date summary of the modalities available to properly assess cardiorenal syndrome.

Interventional management of mitral regurgitation and sleep disordered breathing: "Catching two birds with one stone".

Sleep disordered breathing (SDB), mostly constituting of obstructive and central sleep apnea (OSA and CSA, respectively), is highly prevalent in the general population, and even more among patients with cardiovascular disease, heart failure (HF) and valvular heart disease, such as mitral regurgitation (MR). The coexistence of HF, MR and SDB is associated with worse cardiovascular outcomes and increased morbidity and mortality. Pulmonary congestion, as a result of MR, can exaggerate and worsen the clinical status and symptoms of SDB, while OSA and CSA, through various mechanisms that impair left ventricular dynamics, can promote left ventricular remodelling, mitral annulus dilatation and consequently MR. Regarding treatment, positive airway pressure devices used to ameliorate symptoms in SDB also seem to result in a reduction of MR severity, MR jet fraction and an improvement of left ventricular ejection fraction. However, surgical and transcatheter interventions for MR, and especially transcatheter edge to edge mitral valve repair (TEER), seem to also have a positive effect on SDB, by reducing OSA and CSA-related severity indexes and improving symptom control. The purpose of this review is to provide a comprehensive analysis of the common pathophysiology between SDB and MR, as well as to discuss the available evidence regarding the effect of SDB treatment on MR and the effect of mitral valve surgery or transcatheter repair on both OSA and CSA.

Unravelling the effect of renal denervation on glucose homeostasis: more questions than answers?

Renal Denervation (RDN) is an interventional, endovascular procedure used for the management of hypertension. The procedure itself aims to ablate the renal sympathetic nerves and to interrupt the renal sympathetic nervous system overactivation, thus decreasing blood pressure (BP) levels and total sympathetic drive in the body. Recent favorable evidence for RDN resulted in the procedure being included in the recent European Guidelines for the management of Hypertension, while RDN is considered the third pillar, along with pharmacotherapy, for managing hypertension. Sympathetic overactivation, however, is associated with numerous other pathologies, including diabetes, metabolic syndrome and glycemic control, which are linked to adverse cardiovascular health and outcomes. Therefore, RDN, via ameliorating sympathetic response, could be also proven beneficial for maintaining an euglycemic status in patients with cardiovascular disease, alongside its BP-lowering effects. Several studies have aimed, over the years, to provide evidence regarding the pathophysiological effects of RDN in glucose homeostasis as well as investigate the potential clinical benefits of the procedure in glucose and insulin homeostasis. The purpose of this review is, thus, to analyze the pathophysiological links between the autonomous nervous system and glycemic control, as well as provide an overview of the available preclinical and clinical data regarding the effect of RDN in glycemic control.

LOX-1 Receptor: A Diagnostic Tool and Therapeutic Target in Atherogenesis.

Low-density lipoprotein (LDL) and oxidized LDL (oxLDL) are major contributors to atherogenesis, as endogenous antigens, via several receptors such as LOX 1. A PubMed search was conducted in order to identify relevant articles regarding LOX-1's role in the atherosclerosis, diagnosis, prognostic use and molecules that could be used for therapy. The references of the manuscripts obtained were also reviewed, in order to find additional relevant bibliography. LOX-1 is a lectin-like pattern recognition receptor, mostly expressed in endothelial cells (ECs) which can bind a variety of molecules, including oxLDL and C-reactive protein (CRP). LOX-1 plays a key role in oxLDL's role as a causative agent of atherosclerosis through several pathologic mechanisms, such as oxLDL deposition in the subintima, foam cell formation and endothelial dysfunction. Additionally, LOX-1 acts a scavenger receptor for oxLDL in macrophages and can be responsible for oxLDL uptake, when stimulated. Serum LOX-1 (sLOX-1) has emerged as a new, potential biomarker for diagnosis of acute coronary syndromes, and it seems promising for use along with other common biomarkers in everyday clinical practice. In a therapeutic perspective, natural as well as synthetic molecules exert anti-LOX-1 properties and attain the receptor's pathophysiological effects, thus extensive research is ongoing to further evaluate molecules with therapeutic potential. However, most of these molecules need further trials in order to properly assess their safety and efficacy for clinical use. The aim of this review is to investigate LOX-1 role in atherogenesis and explore its potential as diagnostic tool and therapeutic target.

Intravascular Imaging in Ultra-Low or Zero-Contrast Percutaneous Coronary Interventions: The Time Is Now?

Ultra-low contrast percutaneous coronary interventions (ULPCIs) are a novel field of interventional cardiology, aiming to reduce the risk of contrast-induced nephropathy (CIN), which is a well-described adverse event after angiography. CIN is a well-described adverse event following PCI, especially in high-risk patients, i.e., patients with an already deteriorating renal function or chronic kidney disease, as well as patients of advanced age or requiring an increased amount of contrast during their intervention. Among the techniques described for ULPCI procedures, intravascular imaging guidance seems a promising option, as it allows lesion recognition and characterization, stent implantation, and PCI optimization. Intravascular ultrasound (IVUS) is the modality most commonly used, as it does not require contrast injection, contrary to optical coherence tomography (OCT). Several clinical trials, assessing IVUS in the context of ULPCI, have shown that it can be safely used in this setting while offering a substantial reduction in contrast media volume, as well as renal adverse outcomes. This review aims to describe the need for ULPCI and technical considerations regarding the use of intravascular imaging in this setting, as well as analyze the available evidence from clinical trials regarding the safety and efficacy of IVUS-ULPCI, in order to provide a comprehensive summary for practicing physicians.