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.

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.].

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.

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.

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.

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.

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.

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.

Coronary sinus narrowing therapy: A "Reducer" for angina and beyond.

Refractory Angina (RA) is an increasingly common clinical diagnosis, in which patients unsuitable for further percutaneous or surgical procedures experience anginal symptoms, despite receiving optimal medical therapy. This clinical condition challenges the everyday activities and diminishes the quality of life of these patients. A wide variety of novel therapies for this type of angina are being investigated for clinical use. One of them is coronary sinus narrowing, which is performed as a percutaneous interventional procedure using catheter-delivered device, the Reducer. The device is implanted in the coronary sinus creating a physical narrowing and a pressure gradient in the sinus. This intervention improves the impaired blood flow in the ischemic regions of the heart leading to the relief of the anginal symptoms and, therefore, the overall clinical improvement of these patients. Several clinical trials have established both the safety and efficacy of the coronary sinus Reducer, while ongoing trials are aiming to further establish the procedure's safety and efficiency in both RA and other cardiovascular diseases, such as coronary microvascular dysfunction. This review aims to discuss the pathophysiology and the role of the coronary sinus Reducer in RA, the clinical trials documenting its safety and efficacy, as well as the future perspectives of this procedure among cardiovascular diseases.

Exercise Effects on Left Ventricular Remodeling in Patients with Cardiometabolic Risk Factors.

Left ventricular (LV) remodeling is a dynamic process, which is characterized by changes in ventricular size, shape, and wall thickness, thus altering myocardial geometry and function, and is considered as a negative prognostic factor in patients with heart failure (HF). Hypertension, type 2 diabetes (T2D), and obesity are strongly correlated with the development and the progression of LV remodeling, LV hypertrophy, and LV systolic and/or diastolic dysfunction. Indeed, the beneficial impact of exercise training on primary and secondary prevention of cardiovascular disease (CVD) has been well-established. Recent studies have highlighted that exercise training enhances functional capacity, muscle strength and endurance, cardiac function, and cardiac-related biomarkers among patients with established coronary artery disease (CAD) or HF, thus substantially improving their cardiovascular prognosis, survival rates, and need for rehospitalization. Therefore, in this review article, we discuss the evidence of LV remodeling in patients with cardiometabolic risk factors, such as hypertension, T2D, and obesity, and also highlight the current studies evaluating the effect of exercise training on LV remodeling in these patients.

The effect of SGLT2 inhibitors on the endothelium and the microcirculation: from bench to bedside and beyond.

AIMS: The beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors irrespective of the presence of diabetes mellitus are nowadays well established and they already constitute a significant pillar for the management of heart failure, irrespective of the ejection fraction. The exact underlying mechanisms accountable for these effects, however, remain largely unknown. The direct effect on endothelial function and microcirculation is one of the most well studied. The broad range of studies presented in this review aims to link all available data from the bench to bedside and highlight the existing gaps as well as the future directions in the investigations concerning the effects of SGLT2 inhibitors on the endothelium and the microcirculation. METHODS AND RESULTS: An extensive search has been conducted using the MEDLINE/PubMed database in order to identify the relevant studies. Preclinical data suggest that SGLT2 inhibitors directly affect endothelial function independently of glucose and specifically via several interplaying molecular pathways, resulting in improved vasodilation, increased NO production, enhanced mitochondrial homeostasis, endothelial cell viability, and angiogenesis as well as attenuation of oxidative stress and inflammation. Clinical data systematically confirm this beneficial effect on the endothelium, whereas the evidence concerning the effect on the microcirculation is conflicting. CONCLUSION: Preclinical and clinical studies indicate that SGLT2 inhibitors attenuate endothelial and microvascular dysfunction via a combination of mechanisms, which play a role in their beneficial cardiovascular effect.

Transcatheter Tricuspid Valve Interventions: A Triumph for Transcatheter Procedures?

Tricuspid regurgitation (TR) is a common valvular pathology, estimated to affect 1.6 million people in the United States alone. Even though guidelines recommend either medical therapy or surgical treatment for TR, the misconception of TR as a benign disease along with the high mortality rates of surgical intervention led to undertreating this disease and commonly describing it as a "forgotten" valve. Recently, the development of transcatheter interventions for TR show promising potential for use in the clinical setting. There are currently few approved and numerous tested percutaneously delivered devices, which can be categorized, based on their mechanism of action, to either valve repair or valve replacement procedures. Both procedures were tested in clinical trials and show an echocardiographic reduction in TR sustained for at least 1 year after the procedure, as well as symptom relief and functional improvement of the patients. Device selection should be personalized, taking into consideration the anatomy of each valve and the available options at each heart center. Moreover, appropriate patient selection and timing of the procedure are also crucial for the success of the procedure. In this review, we analyze the clinical trials available for all devices currently approved or tested, aiming to provide a comprehensive summary of the most recent evidence in the field of transcatheter TR interventions.

A network meta-analysis of the antithrombotic strategies in patients with atrial fibrillation and percutaneous coronary interventions: Focus on bleeding.

BACKGROUND: We performed a network meta-analysis of randomized controlled trials comparing non-vitamin K antagonist oral anticoagulant (NOAC)-based versus vitamin K antagonists (VKA)-based regimens in patients with atrial fibrillation (AF) and acute coronary syndromes or PCI, aiming to examine the precise impact of recently established antithrombotic strategies on major bleeding as primary end-point and other safety and efficacy as secondary end-points. METHODS: A literature search was conducted for randomized controlled trials. Our search took place in three major databases. The primary endpoint of our study was bleeding. To combine direct and indirect evidence across trials, a frequentist network meta-analysis with a random-effects model was used. RESULTS: Five studies were found eligible for the meta-analysis enrolling a total of 11,542 patients. Five studies (N = 4903 patients) contributed to the network. Compared to the triple antithrombotic therapy (TAT)-based VKA, only the dual antithrombotic therapy (DAT) based NOAC reduced the bleeding (RR 0.57, 95%CI 0.40-0.82). There was no statistically significant difference between DAT-based VKA (RR = 0.66, 95%CI = 0.40-1.09) or TAT-based NOAC (RR = 0.80, 95%CI = 0.43-1.49). DAT-based NOAC ranked best (P-score = 0.91), followed by DAT-based VKA (P-score = 0.67), TAT-based NOAC (P-score = 0.40), and TAT-based VKA (P-score = 0.03). CONCLUSION: The network meta-analysis of four antithrombotic strategies, demonstrated that in patients with AF undergoing PCI the combination of DAT-based NOAC is associated with a significantly lower risk of major bleeding events. This strategy does not seem to be less effective in terms of prevention of ischemic events compared to the other regimens.