The role of coronary microcirculation in heart failure with preserved ejection fraction: An unceasing odyssey.

Heart failure with preserved ejection fraction (HFpEF) represents an entity with complex pathophysiologic pathways, among which coronary microvascular dysfunction (CMD) is believed to be an important orchestrator. Research in the field of CMD has highlighted impaired vasoreactivity, capillary rarefaction, and inflammation as potential mediators of its development. CMD can be diagnosed via several noninvasive methods including transthoracic echocardiography, cardiac magnetic resonance, and positron emission tomography. Moreover, invasive methods such as coronary flow reserve and index of microcirculatory resistance are commonly employed in the assessment of CMD. As far as the association between CMD and HFpEF is concerned, numerous studies have highlighted the coexistence of CMD in the majority of HFpEF patients. Additionally, patients affected by both conditions may be facing an adverse prognosis. Finally, there is limited evidence suggesting a beneficial effect of renin-angiotensin-aldosterone system blockers, ranolazine, and sodium-glucose cotransporter-2 inhibitors in CMD, with further evidence being awaited regarding the impact of other pharmacotherapies such as anti-inflammatory agents.

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.

Analysis of the quality of reporting of randomized controlled trials in anticoagulant versus antiplatelet medication for venous thromboembolism prophylaxis as governed by the CONSORT statement.

Randomized controlled trials (RCTs) are the gold standard research in evaluating healthcare interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement improves the quality of RCTs in an evidence-based approach. To evaluate the reporting quality of published RCTs concerning the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis according to the CONSORT statement. Electronic databases were searched for English-language RCTs involving patients who received either anticoagulant or antiplatelet medication for prophylaxis of deep vein thrombosis and pulmonary embolism published from 2000 to 2019. Trials were considered eligible when the included patients received either anticoagulant or antiplatelet medication for primary and secondary prevention of deep vein thrombosis or pulmonary embolism and were randomly assigned to at least two treatment arms. Quality of reporting was assessed using a 37-item questionnaire based on the CONSORT 2010 checklist. Reporting was assessed in 2 publication periods (2000-2009) and (2010-2019). The effect of CONSORT statement in high- and low-ranked medical journals, according to their impact factor, has also been evaluated. The search identified 13 eligible articles for analysis. Only 12 of the 37 items of the checklist were addressed in 75% or more of the studies. Most items concerning the methodological issues were reported by fewer than 50% of the studies. Improvements over time were seen for items that assessed the methodological quality with no statistically significant difference. RCTs published in high-ranked journals showed better quality of reporting. Quality of reporting in RCTs focusing on the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research.

A "Snake-Like" Vessel in the Thorax.

We report a congenital extracardiac arteriovenous fistula revealed incidentally in a patient undergoing computed tomographic coronary angiography for angina. This clinical vignette panel describes the origin and the trajectory of this rare vascular lesion.

Multimodality Imaging in a Patient With Double Aortic Arch Undergoing Transcatheter Aortic Valve Implantation.

Double aortic arch is a rare congenital malformation often identified as an incidental finding during routine imaging. In our case, we describe aortic hemodynamics of double aortic arch in a patient with severe aortic stenosis and the procedural process of transcatheter aortic valve implantation.

Multimodality Imaging in a Patient With Double Aortic Arch Undergoing Transcatheter Aortic Valve Implantation: J Am Coll Cardiol Case Rep 2024;29:102224.

[This retracts the article DOI: 10.1016/j.jaccas.2024.102224.].

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.

Hypothermia for Cardioprotection in Acute Coronary Syndrome Patients: From Bench to Bedside.

Early revascularization for patients with acute myocardial infarction (AMI) is of outmost importance in limiting infarct size and associated complications, as well as for improving long-term survival and outcomes. However, reperfusion itself may further damage the myocardium and increase the infarct size, a condition commonly recognized as myocardial reperfusion injury. Several strategies have been developed for limiting the associated with reperfusion myocardial damage, including hypothermia. Hypothermia has been shown to limit the degree of infarct size increase, when started before reperfusion, in several animal models. Systemic hypothermia, however, failed to show any benefit, due to adverse events and potentially insufficient myocardial cooling. Recently, the novel technique of intracoronary selective hypothermia is being tested, with preclinical and clinical results being of particular interest. Therefore, in this review, we will describe the pathophysiology of myocardial reperfusion injury and the cardioprotective mechanics of hypothermia, report the animal and clinical evidence in both systemic and selective hypothermia and discuss the potential future directions and clinical perspectives in the context of cardioprotection for myocardial reperfusion injury.

ANOCA updated: From pathophysiology to modern clinical practice.

Lately, a large number of stable ischemic patients, with no obstructed coronary arteries are being diagnosed. Despite this condition, which is being described as angina with no obstructive coronary arteries (ANOCA), was thought to be benign, recent evidence report that it is associated with increased risk for adverse cardiovascular outcomes. ANOCA is more frequent in women and, pathophysiologically, it is predominantly related with microvascular dysfunction, while other factors, such as endothelial dysfunction, inflammation and autonomic nervous system seem to also play a major role to its development, while other studies implicate ANOCA and microvascular dysfunction in the pathogenesis of heart failure with preserved ejection fraction. For establishing an ANOCA diagnosis, measurement including coronary flow reserve (CFR), microvascular resistance (IMR) and hyperemic microvascular resistance (HMR) are mostly used in clinical practice. In addition, new modalities, such as optical coherence tomography (OCT) are being tested and show promising results for future diagnostic use. Regarding management, pharmacotherapy consists of a wide selection of drugs, according to the respected pathophysiology of the disease (vasospastic angina or microvascular dysfunction), while research for new treatment options including interventional techniques, is currently ongoing. This review, therefore, aims to provide a comprehensive analysis of all aspects related to ANOCA, from pathophysiology to clinical managements, as well as clinical implications and suggestions for future research efforts, which will help advance our understanding of the syndrome and establish more, evidence-based, therapies.

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.

Left Atrium: A New Prognostic Marker and Therapeutic Target in Secondary Mitral Regurgitation?

Mitral regurgitation (MR) is one of the most common valvular abnormalities worldwide and can be subdivided into primary and secondary causes. Atrial MR consists of a novel type of secondary MR (SMR), most often observed in patients with AF and heart failure with preserved ejection fraction. The main pathophysiological mechanism of atrial MR is mitral valve annular dilatation. Recently published studies have highlighted the clinical significance of left atrium (LA) evaluation in the early diagnosis and prognosis of patients with primary MR. However, there are little data regarding the role of the LA in SMR. The present literature review aims to elucidate the use of the echocardiographic parameters regarding LA evaluation in the prognosis prediction and therapeutic strategy of patients with SMR.

Transcatheter Structural Heart Interventions in the Acute Setting: An Emerging Indication.

Structural heart disease is increasingly prevalent in the general population, especially in patients of increased age. Recent advances in transcatheter structural heart interventions have gained a significant following and are now considered a mainstay option for managing stable valvular disease. However, the concept of transcatheter interventions has also been tested in acute settings by several investigators, especially in cases where valvular disease comes as a result of acute ischemia or in the context of acute decompensated heart failure. Tested interventions include both the mitral and aortic valve, mostly evaluating mitral transcatheter edge-to-edge repair and transcatheter aortic valve implantation, respectively. This review is going to focus on the use of acute structural heart interventions in the emergent setting, and it will delineate the available data and provide a meaningful discussion on the optimal patient phenotype and future directions of the field.

The Modern Clinician as an "Argonaut" Guiding Through the "Symplegades" of Evidence for PFO Closure in Patients With Migraine.

Patent foramen ovale (PFO) has been associated with migraine, especially migraine with aura, and 30-50% of individuals with migraine with aura have a PFO, suggesting it could be more than just an "innocent bystander''. Observational data showed a reduction of the frequency and severity of migraine attacks, particularly those with aura, following transcatheter PFO closure for established indications. Three small randomized controlled trials have demonstrated significant benefits of PFO closure in most of their secondary endpoints, such as reductions in the mean number of monthly migraine attacks and migraine days. Since a significant proportion of patients experience important side effects from traditional migraine medications and newer highly effective migraine prevention strategies may need to be instituted. PFO closure could in this regard to be a valuable add-on in the armamentarium of migraine treatment, improving the quality of life by alleviating the need for medications. The effect of percutaneous PFO closure on migraine treatment is needed to be clarified. As the underlying pathophysiology remains poorly understood and largely hypothetical, future investigations, focusing on the causal relationship between PFO and migraine, will help to define the subgroup of patients most likely to benefit from PFO closure. More accurate patient recruitment may lead to greater postprocedural benefits and more significant symptom improvement. Additionally, randomized controlled trials need to be reported adequately with more realistic endpoints, sufficient duration of follow-up, and statistical power to detect differences between closure and placebo groups to ensure precise and reliable findings.

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.

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.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes.

Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting.

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.