High systemic inflammation as a novel cardiovascular risk factor and target for anti-cytokine therapy: comment regarding the triglyceride glucose index.

In the last century, there has been more than enough research that proved the association of high lipid and glucose levels with cardiovascular disease, thus establishing the current well-known traditional cardiovascular risk factors such as dyslipidemia, diabetes, and metabolic syndrome. Hence, these cardiovascular risk factors are target therapy for glucose and lipid-lowering agents to prevent adverse cardiovascular events. However, despite controlling the lipid and glucose levels, some studies demonstrated the subclinical atherosclerosis suggesting that these cardiovascular risk factors alone cannot account for the entire atherosclerosis burden. In the last years, large-scale clinical trials demonstrated the operation of the inflammatory pathway in atherosclerotic cardiovascular disease (ASCVD) by the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. In this regard, some studies that use antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, have been shown to reduce the risk of adverse cardiovascular events in patients with previous coronary artery disease. In this regard, the U.S. Food and Drug Administration (FDA) approved the use of colchicine 0.5 mg once daily for reducing cardiovascular events in patients who have established ASCVD and high residual systemic inflammation. Therefore, measuring the systemic inflammation can improve the cardiovascular risk assessment and identify the subsets of patients that will benefit from anti-cytokine therapy after diagnosis of ASCVD or after myocardial revascularization.

Cannon A wave validation as a diagnostic tool in paroxysmal supraventricular tachycardias.

OBJECTIVE: The presence of cannon A waves, the so called "frog sign", has traditionally been considered diagnostic of atrioventricular nodal re-entrant tachycardia (AVNRT). Nevertheless, it has never been systematically evaluated. The aim of this study is to assess the independent diagnostic utility of cannon A waves in the differential diagnosis of supraventricular tachycardias (SVTs). METHODS: We prospectively included 100 patients who underwent an electrophysiology (EP) study for SVT. The right jugular venous pulse was recorded during the study. In 61 patients, invasive central venous pressure (CVP) was registered as well. CVP increase is thought to be related with the timing between atria and ventricle depolarization; two groups were prespecified, the short VA interval tachycardias (including typical AVNRT and atrioventricular reciprocating tachycardia (AVRT) mediated by a septal accessory pathway) and the long VA interval tachycardias (including atypical AVNRT and AVRT mediated by a left free wall accessory pathway). RESULTS: The relationship between cannon A waves and AVNRT did not reach the statistical significance (OR: 3.01; p = .058); On the other hand, it was clearly associated with the final diagnosis of a short VA interval tachycardia (OR: 10.21; p < .001). CVP increase showed an inversely proportional relationship with the VA interval during tachycardia (b = -.020; p < .001). CVP increase was larger in cases of AVNRT (4.0 mmHg vs. 1.2 mmHg; p < .001) and short VA interval tachycardias (3.9 mmHg vs. 1.2 mmHg; p < .001). CONCLUSION: The presence of cannon A waves is associated with the final diagnosis of short VA interval tachycardias.

The clinical anatomy of the atrioventricular conduction axis.

It is axiomatic that the chances of achieving accurate capture of the conduction axis and its fascicles will be optimized by equally accurate knowledge of the relationship of the components to the recognizable cardiac landmarks, and we find it surprising that acknowledged experts should continue to use drawings that fall short in terms of anatomical accuracy. The accuracy achieved by Sunao Tawara (1906) in showing the location of the atrioventricular conduction axis is little short of astounding. Our purpose in bringing this to current attention is to question the need of the experts to have produced such inaccurate representations, since the findings of Tawara have been extensively endorsed in very recent years. The recent studies do no more than point to the amazing accuracy of the initial account of Tawara. At the same time, we draw attention to the findings described in the middle of the 20th century by Ivan Mahaim (1947). These observations have tended to be ignored in recent accounts. They are, perhaps, of equal significance to those seeking specifically to pace the left fascicles of the branching atrioventricular bundle.

Neutrophil-to-lymphocyte ratio an inflammatory biomarker, and prognostic marker in heart failure, cardiovascular disease and chronic inflammatory diseases: New insights for a potential predictor of anti-cytokine therapy responsiveness.

In the 20th century, research focused on cholesterol and lipoproteins as the key mechanism in establishing atherosclerotic cardiovascular disease (ASCVD). Given that some studies demonstrated subclinical atherosclerosis in subjects without conventional cardiovascular risk factors, the elevated low-density lipoprotein (LDL) levels alone cannot account for the entire burden of atherosclerosis. Hence, large-scale clinical trials demonstrated the operation of immune and inflammatory pathways in ASCVD. In this regard, the evidence establishes that cells of the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. Besides, basic science studies have identified proatherogenic cytokines such as interleukin (IL)-1, IL-12, and IL-18. In this regard, some studies showed that antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, can reduce the risk of major cardiovascular adverse events. The neutrophils play a key role in the innate immune system, representing the acute phase of an inflammatory response. In contrast, lymphocytes represent the adaptive immune system and promote the induction of autoimmune inflammation, especially in the chronic inflammatory response. Through the literature review, we will highlight the inflammatory pathway for the physiopathology of ASCVD, HF, and COVID-19. In this regard, the neutrophil-to-lymphocyte ratio (NLR) integrates the innate immune and adaptive immune systems, making the NLR a biomarker of inflammation. In addition, we provided an update on the evidence showing that high NLR is associated with worse prognosis in heart failure (HF), ASCVD, and COVID-19, as well as their clinical applications showing that the normalization of NLR after anti-cytokine therapy is a potential predictor of therapy responsiveness and is associated with reduction of major adverse cardiovascular events.

Decrement Evoked Potential (DEEP) Mapping of the Atria: Unmasking Atrial Fibrillation Substrate.

BACKGROUND: Atrial myopathy may underlie the progression of atrial fibrillation (AF) from a treatable disease to an irreversible condition with poor ablation outcomes. Electrophysiological methods to unmask areas prone to re-entry initiation could be key to defining latent atrial myopathy. METHODS: Consecutive patients referred for AF ablation were prospectively included at four institutions. Decrement evoked potential mapping (DEEP) was performed in eight left atrial sites and five right atrial sites, from two different pacing locations (endocardially from the left atrial appendage, epicardially from the proximal coronary sinus). The electrograms (EGMs) during S1 600 ms drive and after an extra stimulus (S2 at +30 ms above atrial refractoriness) were studied at each location and assessed for decremental properties. Follow-up was 12 months. RESULTS: Seventy-four patients were included and 85% had persistent AF. A total of 17,614 EGMs were individually analysed and measured. Nine percent of the EGMs showed DEEP properties (local delay of >10 ms after S2) with a mean decrement of 33±26 ms. DEEPs were more frequent in the left atrium than the right atrium (9.4% vs 8.0%; p<0.001) and more prevalent in persistent AF patients than paroxysmal AF patients (9.8% vs 4.6% p=0.001). Atrial DEEPs were more frequently unmasked in normal bipolar voltage areas and by epicardial pacing than endocardial pacing (9.6% vs 8.4%, respectively; p=0.004). Within the left atrium, the roof had the highest prevalence of DEEP EGMs. CONCLUSIONS: DEEP mapping of both atria is useful for highlighting areas with a tendency for unidirectional block and re-entry initiation. Those areas are more easily unmasked by epicardial pacing from the coronary sinus and more prevalent in persistent AF patients than in paroxysmal AF patients.

Pacing of the specialized His-Purkinje conduction system: 'back to the future'.

The conduction system of the human heart is composed of specialized cardiomyocytes that initiate and propagate the electric impulse with consequent rhythmic and synchronized contraction of the atria and ventricles, resulting in the normal cardiac cycle. Although the His-Purkinje system (HPS) was already described more than a century ago, there has been a recent resurgence of conduction system pacing (CSP), where pacing leads are positioned in the His bundle region and left bundle branch area to provide physiological cardiac activation as alternatives to the unnatural myocardial stimulation obtained with conventional right ventricular and biventricular pacing. In this review, we describe the fundamental anatomical and pathophysiological aspects of the specialized HPS along with the CSP technique's nuts and bolts to highlight its potential benefits in everyday clinical practice.

White-Matter Lesions and Cortical Cerebral Blood Flow Evaluation by 3D Arterial Spin-Labeled Perfusion MRI in Asymptomatic Divers: Correlation with Patent Foramen Ovale Ocurrence.

Cerebral white-matter lesions (cWML) can be caused by dilation of Virchow-Robin spaces or may correspond to true lacunar ischemic lesions. The aim of our study was to evaluate in asymptomatic divers the relationship between the presence of patent foramen ovale (PFO) and cWML, as well as their possible effects on cortical cerebral blood flow (CBF) by magnetic resonance (MRI) through the arterial spin labeling (ASL) sequence. Transthoracic echocardiography was performed for the identification of PFO, and cerebral magnetic resonance including the 3D-ASL sequence for CBF quantification. Thirty-eight divers, with a mean age 45.8 ± 8.6 years, were included. Nineteen healthy volunteers, mean age 41 ± 15.2 years, served as the control group. A total of 28.9% of divers had completed more than 1000 dives. It was found that 26.3% of divers presented with PFO in the echocardiographic study. cWML was evidenced in 10.5% of diver MRI studies. There was no statistically significant relationship between the presence of PFO and cWML (p = 0.95). We observed a lower blood flow in all brain areas assessed by the 3D-ASL sequence in the group of divers, compared with the control group. We did not find statistical differences in CBF as a function of the presence or absence of PFO, number of dives, or cWML evidence.

Comparative Cardiac Magnetic Resonance-Based Feature Tracking and Deep-Learning Strain Assessment in Patients Hospitalized for Acute Myocarditis.

This study sought to examine the correlation between left ventricular (LV) myocardial feature tracking (FT) and deep learning-based strain (DLS) analysis in the diagnostic (CMRd) and follow-up (CMRf) cardiac magnetic resonance imaging of patients with acute myocarditis. The retrospective study included 17 patients with acute myocarditis and 20 healthy controls. The CMRd took place within 14 days of symptom onset, while the CMRf took place at least 2 months after the event. The global-circumferential FT (FTc) and global-circumferential DLS (DLSc) were analyzed. The continuous variables were compared using paired t-tests or the Wilcoxon test, whereas Pearson's test or Spearman's test was used to evaluate the correlation between the continuous variables. The time between the CMRd and CMRf was 5 months [3-11]. The LV ejection fraction (LVEF) was 55 ± 6 and 59 ± 4%, p = 0.008, respectively, and 94.1% of the patients showed late gadolinium enhancement (LGE) and myocardial edema on the CMRd. Significantly lower FTc (-16.1 ± 2.2% vs. -18.9 ± 1.9%, p = 0.001) and DLSc (-38.1 ± 5.2% vs. -41.3 ± 4.5%, p = 0.015) were observed with respect to the controls. Significant increases in the FTc (-16.1 ± 2.2 vs. -17.5 ± 1.9%, p = 0.016) and DLSc (-38.1 ± 5.2 vs. -39.8 ± 3.9%, p = 0.049) were found between the CMRd and CMRf, which were unrelated to the LGE. The LVEF correlated well with the FTc (r = 0.840) and DLSc (r = 0.760). Both techniques had excellent reproducibility, with high intra- (FTc = 0.980, DLSc = 1.000) and inter-observer (FTc = 0.970, DLSc = 0.980) correlation. There was correlation between the LV DLSc/FTc and LVEF in the patients with acute myocarditis according to the CMRd and CMRf.

Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings: JACC: CardioOncology State-of-the-Art Review.

Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors.

4D-Flow Cardiac Magnetic Resonance Imaging in Chronic Aortic Dissection Assessment: A Powerful Qualiquantitative Diagnostic Tool.

4-dimensional-flow cardiac magnetic resonance in patients with aortic dissection in chronic/post repair phase as a complementary diagnostic tool for anatomic-functional evaluation. Quali-quantitative analysis of 3 patients with this pathology clearly showing the true/false lumen, quantitative flow in false lumen, and helping in discerning lumen origin from different arterial vessels. (Level of Difficulty: Advanced.).

A papillary fibroelastoma with myxoma camouflage: a case report.

Background: Benign cardiac tumours are infrequent in clinical practice and, of these, cardiac myxoma is the one with the highest incidence. Given that a left intraventricular presentation is rare, other differential diagnoses such as papillary fibroelastoma should be considered. Case summary: A 73-year-old woman patient with cardiac mass detected in transthoracic echocardiography (TTE) after a transient ischaemic attack. At TTE 2D-3D, a left intraventricular mass anchored at the level of the anterolateral papillary muscle was detected. Subsequently, cardiac magnetic resonance (CMR) was performed for mass characterization. This revealed behaviour in T1 (isointense with respect to myocardium), T2 (hyperintense), very prolonged T1-mapping (1848 msg), and T2-mapping (161 msg) values, without gadolinium uptake in the first-pass perfusion sequence, but with intense uptake in late enhancement sequences. Previous findings were compatible with a diagnosis of papillary fibroelastoma. The mass was resected intraoperatively and, although its macroscopic appearance pointed to a diagnosis of cardiac myxoma, it was finally confirmed to be a papillary fibroelastoma by pathological anatomy. Discussion: In cases where the size of the mass and its mobility allow tissue characterization by CMR, a diagnosis of papillary fibroelastoma and its differentiation with cardiac myxoma are feasible by this cardiac imaging technique.

Anatomy of the left atrial appendage for the interventional cardiologist.

Exact knowledge of the anatomy of the left atrial appendage (LAA) is crucial for LAA isolation by catheter ablation and for interventional LAA occlusion in patients with atrial fibrillation. This review outlines the current anatomical understanding of LAA morphology from ostium to distal lobes, myocardial fiber orientation and wall structure, and adjacent structures such as the left upper pulmonary vein with the Coumadin ridge, the circumflex artery with its side branches, the aortic root, pulmonary artery, and the pericardial space. Insight into these details will facilitate these interventions and reduce the risk of complications.

Anatomical knowledge for the ablation of left and right atrial flutter.

The different forms of atrial flutter (AFL) and atrial macroreentrant tachycardias are strongly related to the atrial anatomy in structurally normal atria, and even more so in patients with dilated chambers or with previous interventions. Atrial anatomy, macro- and microscopic tissue disposition including myocardial fibers, conduction system and connective tissue is complex. This review summarizes knowledge of atrial anatomy for the interventional electrophysiologist to better understand the pathophysiology of and ablation options for these complex arrhythmias, as well as to perform catheter ablation procedures safely and effectively.

Miniseries 2-Septal and paraseptal accessory pathways-Part IV: Inferior paraseptal accessory pathways-lessons from surgical and catheter ablation.

Surgeons and electrophysiologists performing accessory pathway ablation procedures have used the term 'posteroseptal' region. This area, however, is neither septal nor posterior, but paraseptal and inferior; paraseptal because it includes the fibro-adipose tissues filling the pyramidal space and not the muscular septum itself and inferior because it is part of the heart adjacent to the diaphragm. It should properly be described, therefore, as being inferior and paraseptal. Pathways in this region can be ablated at three areas, which we term right inferior, mid-inferior, and left inferior paraseptal. The right- and left inferior paraseptal pathways connect the right and left atrial vestibules with the right and left paraseptal segments of the parietal ventricular walls. The mid-inferior paraseptal pathways take a subepicardial course from the myocardial sleeves surrounding the coronary sinus and its tributaries. Our review addresses the evolution of the anatomical concept of the inferior paraseptal region derived from surgical and catheter ablation procedures. We also highlight the limitations of the 12-lead electrocardiogram in identifying, without catheter electrode mapping, which are the pathways that can be ablated without a coronary sinus, or left heart approach.

Miniseries 2-Septal and paraseptal accessory pathways-Part I: The anatomic basis for the understanding of para-Hisian accessory atrioventricular pathways.

AIMS: Although the anatomy of the atrioventricular conduction axis was well described over a century ago, the precise arrangement in the regions surrounding its transition from the atrioventricular node to the so-called bundle of His remain uncertain. We aimed to clarify these relationships. METHODS AND RESULTS: We have used our various datasets to examine the development and anatomical arrangement of the atrioventricular conduction axis, paying particular attention to the regions surrounding the point of penetration of the bundle of His. It is the areas directly adjacent to the transition of the atrioventricular conduction axis from the atrioventricular node to the non-branching atrioventricular bundle that constitute the para-Hisian areas. The atrioventricular conduction axis itself traverses the membranous part of the ventricular septum as it extends from the node to become the bundle, but the para-Hisian areas themselves are paraseptal. This is because they incorporate the fibrofatty tissues of the inferior pyramidal space and the superior atrioventricular groove. In this initial overarching review, we summarize the developmental and anatomical features of these areas along with the location and landmarks of the atrioventricular conduction axis. We emphasize the relationships between the inferior pyramidal space and the infero-septal recess of the subaortic outflow tract. The details are then explored in greater detail in the additional reviews provided within our miniseries. CONCLUSION: Our anatomical findings, described here, provide the basis for our concomitant clinical review of the so-called para-Hisian arrhythmias. The findings also provide the basis for understanding the other variants of ventricular pre-excitation.

Miniseries 2-Septal and paraseptal accessory pathways-Part III: Mid-paraseptal accessory pathways-revisiting bypass tracts crossing the pyramidal space.

The mid-paraseptal region corresponds to the portion of the pyramidal space whose right atrial aspect is known as the triangle of Koch. The superior area of this mid-paraseptal region is also para-Hisian, and is close to the compact atrioventricular node and the His bundle. The inferior sector of the mid-paraseptal area is unrelated to the normal atrioventricular conduction pathways. It is, therefore, a safe zone in which, if necessary, to perform catheter ablation. The middle part of the mid-paraseptal zone may, however, in some patients, house components of the compact atrioventricular node. This suggests the need for adopting a prudent attitude when considering catheter ablation in this area. The inferior extensions of the atrioventricular node, which may represent the substrate for the slow atrioventricular nodal pathway, take their course through the middle, and even the inferior, sectors of the mid-paraseptal region. In this review, we contend that the middle and inferior areas of the mid-paraseptal region correspond to what, in the past, was labelled by most groups as the 'midseptal' zone. We describe the electrocardiographic patterns observed during pre-excitation and orthodromic reciprocating tachycardia in patients with pathways ablated in the middle or inferior sectors of the region. We discuss the modification of the ventriculo-atrial conduction times during tachycardia after the development of bundle branch block aberrancy. We conclude that the so-called 'intermediate septal' pathways, as described in the era of surgical ablation, were insufficiently characterized. They should not be considered the surrogate of the 'midseptal' pathways defined using endocardial catheter electrode mapping.