Osteopontin stabilization and collagen containment slows amorphous calcium phosphate transformation during human aortic valve leaflet calcification.

Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100's nm- to 1 µm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants.

Cardiac blood vessels and irreversible electroporation: findings from pulsed field ablation.

The clinical use of irreversible electroporation in invasive cardiac laboratories, termed pulsed field ablation (PFA), is gaining early enthusiasm among electrophysiologists for the management of both atrial and ventricular arrhythmogenic substrates. Though electroporation is regularly employed in other branches of science and medicine, concerns regarding the acute and permanent vascular effects of PFA remain. This comprehensive review aims to summarize the preclinical and adult clinical data published to date on PFA's effects on pulmonary veins and coronary arteries. These data will be contrasted with the incidences of iatrogenic pulmonary vein stenosis and coronary artery injury secondary to thermal cardiac ablation modalities, namely radiofrequency energy, laser energy, and liquid nitrogen-based cryoablation.

Innervation of the coronary arteries and its role in controlling microvascular resistance.

The coronary circulation plays a crucial role in balancing myocardial perfusion and oxygen demand to prevent myocardial ischemia. Extravascular compressive forces, coronary perfusion pressure, and microvascular resistance are involved to regulate coronary blood flow throughout the cardiac cycle. Autoregulation of the coronary blood flow through dynamic adjustment of microvascular resistance is maintained by complex interactions among mechanical, endothelial, metabolic, neural, and hormonal mechanisms. This review focuses on the neural mechanism. Anatomy and physiology of the coronary arterial innervation have been extensively investigated using animal models. However, findings in the animal heart have limited applicability to the human heart as cardiac innervation is generally highly variable among species. So far, limited data are available on the human coronary artery innervation, rendering multiple questions unresolved. Recently, the clinical entity of ischemia with non-obstructive coronary arteries has been proposed, characterized by microvascular dysfunction involving abnormal vasoconstriction and impaired vasodilation. Thus, measurement of microvascular resistance has become a standard diagnostic for patients without significant stenosis in the epicardial coronary arteries. Neural mechanism is likely to play a pivotal role, supported by the efficacy of cardiac sympathetic denervation to control symptoms in patients with angina. Therefore, understanding the coronary artery innervation and control of microvascular resistance of the human heart is increasingly important for cardiologists for diagnosis and to select appropriate therapeutic options. Advancement in this field can lead to innovations in diagnostic and therapeutic approaches for coronary artery diseases.

Insights Into Interaction Between Clip Device and the Mitral Valve Apparatus in the Human Heart.

Precise appreciation of the 3-dimensional relationship between the edge-to-edge clips and mitral valve apparatus remains clinically challenging. We demonstrate the images of clips observed in situ 4 years after implantation. Detailed observation from this case helps improve our understanding of 3-dimensional clinical cardiac anatomy related to transcatheter edge-to-edge mitral valve repair. (Level of Difficulty: Intermediate.).

Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study.

BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Understanding Cardiac Anatomy and Imaging to Improve Safety of Procedures: The Right Ventricle.

Right ventricular perforation is a catastrophic complication of catheter-based intracardiac interventions. In this context, appreciation of 5 attachments of the right ventricle to the aortoventricular unit is essential to recognize extent of right ventricular free wall. We herein present progressive dissection and virtual and photographic endoscopic images of the hearts without distortion. Real dissection images show us how and where to avoid this complication by indicating the true muscular component of the ventricular septum. Both virtual and photographic endoscopic images, when combined with transillumination, beautifully shows the thin wall regions and trabeculations with unprecedented clarity. We believe recognition of these anatomical nuances can reduce the likelihood of right ventricular perforation.

Photogrammetry of Perfusion-Fixed Heart: Innovative Approach to Study 3-Dimensional Cardiac Anatomy.

Photogrammetry generates a 3-dimensional high-resolution model from multiple 2-dimensional photographs. Herein, we demonstrate a photogrammetry of a perfusion-fixed cardiac sample around the left ventricular summit. The single photogrammetric model can be observed from almost all directions and illustrates important anatomical features for the general cardiologist. (Level of Difficulty: Advanced.).

Ischemia-induced ventricular proarrhythmia and cardiovascular autonomic dysreflexia after cardioneuroablation.

BACKGROUND: Cardioneuroablation (CNA) is an attractive treatment of vasovagal syncope. Its long-term efficacy and safety remain unknown. OBJECTIVE: The purpose of this study was to develop a chronic porcine model of CNA to examine the susceptibility to ventricular tachyarrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) and cardiac autonomic function after CNA. METHODS: A percutaneous CNA model was developed by ablation of left- and right-sided ganglionated plexi (n = 5), confirmed by histology. Reproducible bilateral vagal denervation was confirmed after CNA by extracardiac vagal nerve stimulation (VNS) and histology. Chronic studies included 16 pigs randomized to CNA (n = 8) and sham ablation (n = 8, Control). After 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation and direct VNS, respectively, and proarrhythmic potential after left anterior descending (LAD) coronary artery ligation. RESULTS: After CNA, extracardiac VNS responses remained abolished for 6 weeks despite ganglia remaining in ablated ganglionated plexi. In the CNA group, direct VNS resulted in paradoxical increases in blood pressure, but not in sham-ablated animals (CNA group vs sham group: 8.36% ± 7.0% vs -4.83% ± 8.7%, respectively; P = .009). Left sympathetic chain stimulation (8 Hz) induced significant corrected QT interval prolongation in the CNA group vs the sham group (11.23% ± 4.0% vs 1.49% ± 4.0%, respectively; P < .001). VT/VF after LAD ligation was more prevalent and occurred earlier in the CNA group than in the control group (61.44 ± 73.7 seconds vs 245.11 ± 104.0 seconds, respectively; P = .002). CONCLUSION: Cardiac vagal denervation is maintained long-term after CNA in a porcine model. However, chronic CNA was associated with cardiovascular dysreflexia, diminished cardioprotective effects of cardiac vagal tone, and increased susceptibility to VT/VF in ischemia. These potential long-term negative effects of CNA suggest the need for rigorous clinical studies on CNA.

Cardiac Conduction System Pacing: A Comprehensive Update.

The field of cardiac pacing has changed rapidly in the last several years. Since the initial description of His bundle pacing targeting the conduction system, recent advances in pacing the left bundle branch and its fascicles have evolved. The field and investigators' knowledge of conduction system pacing including relevant anatomy and physiology has advanced significantly. The aim of this review is to provide a comprehensive update on recent advances in conduction system pacing.

Transcatheter Aortic Valve Replacement Guided by Preprocedural Simulation of Fluoroscopic Location of the Membranous Septum.

We show the virtual simulation of the fluoroscopic location of the membranous septum using preprocedural cardiac computed tomographic data sets. Recognizing the risk distance before the procedure can help individualize implantation strategy to reduce the risk of atrioventricular conduction axis damage during transcatheter aortic valve replacement. (Level of Difficulty: Advanced.).

Ventricular Parasystole in Cardiomyopathy Patients: A Link Between His-Purkinje System Damage and Ventricular Fibrillation.

BACKGROUND: The clinical relevance and prognostic implications of ventricular parasystole are unknown. OBJECTIVES: This study sought to assess the prevalence of ventricular parasystole in patients with implantable cardioverter-defibrillators (ICDs) and ventricular parasystole's association with ventricular arrhythmias and conduction system abnormalities. METHODS: This study retrospectively evaluated patients who underwent ICD interrogation at a single center between June 1, 2019, and August 31, 2020, and reviewed all available ICD and electrocardiogram data. This study identified patients with ventricular parasystole and compared the prevalence of ventricular fibrillation (VF), ventricular tachycardia (VT), and new conduction system abnormalities in those with ≥5 years of intrinsic QRS-complex electrocardiograms to those without parasystole. RESULTS: This study included 374 patients (age 57 ± 21 years, 72% male, 45% nonischemic, 32% ischemic cardiomyopathy), of which, 104 (28%) had VT only, 39 (10%) VF only, and 10 (3%) both VT/VF. Ventricular parasystole was identified in 33 patients (9%); parasystolic foci were predominantly from the His-Purkinje system. Compared with those without parasystole, patients with parasystole had a significantly higher rate of VF (36% vs 11%; P < 0.01), but not VT (42% vs 29%; P = 0.12). Patients with parasystole, compared with those without parasystole, had a higher prevalence of new conduction abnormalities, particularly progressive intraventricular conduction delay (11 of 18 [61%] vs 12 of 83 [14%]; P < 0.01) and new right bundle branch block (4 of 18 [22%] vs 1 of 83 [1%]; P < 0.01). CONCLUSIONS: Ventricular parasystole was strongly associated with new conduction system abnormalities and VF in patients who have cardiomyopathy with ICDs, suggesting a potential link between VF and His-Purkinje damage in this patient population.