Towards prevention of re-entrant arrhythmias: Injectable hydrogel electrodes enable direct capture of previously inaccessible cardiac tissues

Re–entrant arrhythmias – the leading cause of sudden cardiac death – are caused by diseased and delayed myocardial conduction. Access to the coronary veins that cross the culprit scarred regions where re–entry originates provides improved pacing to prevent ventricular arrhythmias and circumvent the need for painful defibrillation, risky cardiac ablation, or toxic and often ineffective antiarrhythmic medications. To date, this goal has not been achieved due to the lack of pacing electrodes which are small or focal enough to navigate these tributaries. We have developed an injectable conductive hydrogel that can fill the epicardial coronary veins and their mid–myocardial tributaries. When connected to a standard pacing lead, these injected hydrogels can be converted into flexible electrodes that directly pace the previously inaccessible mid–myocardial tissue. In our two–component system, hydrogel precursor solutions can be injected through a dual lumen catheter in a minimally invasive deployment strategy to provide direct access to the diseased regions with relative precision and ease. Mixing of the two solutions upon injection into the vein activates redox–initiated crosslinking of the gel for rapid in situ cure without an external stimulus. An ex vivo porcine model was used to identify the requisite viscosity and cure rate for gel retention and homogeneity. Ionic species added to the hydrogel precursor solutions conferred conductivity above target myocardium values that was retained after implantation. Successful in vivo deployment demonstrated that the hydrogel electrode filled the anterior interventricular vein with extension into the septal (mid–myocardial) venous tributaries, far deeper than current technologies allow. In addition to successful capture and pacing of the porcine heart, analysis of surface ECG tracings revealed a novel pacing paradigm not observed in traditional single–point pacing: capture of extensive swaths of the native conduction system. This is the first report of an injectable electrode used to successfully pace the mid–myocardium and mimic physiologic conduction. As such, this injectable hydrogel electrode can be deployed to any region affected by prior myocardial infarction and consequent scar tissue to provide a reliable pacing modality that most closely resembles native conduction.

Morphological features of the venous bed of the heart of the Baikal seal

The article describes the features of venous blood outflow from the heart in the Baikal seal. The objects for the study were corrosion preparations of 11 hearts of the Baikal seal aged from 1 month to 10 years. In our research we used the methods of preparation, filling of vessels with the use of "Kudo" mounting foam, photographing and sketching the branching of vessels. It was established that in the Baikal seal, the outflow of venous blood occurs through the prominent coronary sinus and the large, intermediate, oblique vein of the left atrium, the middle and right heart veins that flow into it. In 18.2% of hearts, a coronary valve was found at the border of the great heart vein and the coronary sinus. The great heart vein begins above the apices of the heart and is formed from the fusing of the 6-11 collateral veins of the wall of the right ventricle, the venous pericardial plexus, and 9-16 branches on the side of the left ventricle. The most variable is the intermediate (marginal) branch, which in most cases has only one branch, however, in 18.2% of cases there are two ones or in 9.1% of cases, there are intermediate branches with a common trunk. The middle vein of the heart is located in the sub-sinus sulcus and anastomoses with the branch of the great vein of the heart, in 9.1% of cases, the valve of the coronary sinus was found at the border with the coronary sinus. The right veins of the heart have 5-6 branches, among which the marginal ones are the most prominent. 27.3% of Baikal seals have a venous sinus formed from the fusion of the middle and right coronary veins, as well as a duct connecting the large cardiac vein with this sinus.

Morphometric Characterization of Human Coronary Veins and Subvenous Epicardial Adipose Tissue—Implications for Cardiac Resynchronization Therapy Leads

Subvenous epicardial fat tissue (SEAT), which acts as an electrical insulation, and the venous diameter (VD) both constitute histomorphological challenges for optimal application and lead design in cardiac synchronization therapy (CRT). In this study, we characterized the morphology of human coronary veins to improve the technical design of future CRT systems and to optimize the application of CRT leads. We retrospectively analyzed data from cardiac computed tomography (CT) of 53 patients and did studies of 14 human hearts using the postmortem freeze section technique and micro CT. Morphometric parameters (tributary distances, offspring angles, luminal VD, and SEAT thickness) were assessed. The left posterior ventricular vein (VVSP) had a mean proximal VD of 4.0 ± 1.4 mm, the left marginal vein (VMS) of 3.2 ± 1.5 mm and the anterior interventricular vein (VIA) of 3.9 ± 1.3 mm. More distally (5 cm), VDs decreased to 2.4 ± 0.6 mm, 2.3 ± 0.7 mm, and 2.4 ± 0.6 mm, respectively. In their proximal portions (15 mm), veins possessed mean SEAT thicknesses of 3.2 ± 2.4 (VVSP), 3.4 ± 2.4 mm (VMS), and 4.2 ± 2.8 mm (VIA), respectively. More distally (20–70 mm), mean SEAT thicknesses decreased to alternating low levels of 1.3 ± 1.1 mm (VVSP), 1.7 ± 1.1 mm (VMS), and 4.3 ± 2.6 mm (VIA), respectively. In contrast to the VD, SEAT thicknesses alternated along the further distal vein course and did not display a continuous decrease. Besides the CRT responsiveness of different areas of the LV myocardium, SEAT is a relevant electrophysiological factor in CRT, potentially interfering with sensing and pacing. A sufficient VD is crucial for successful CRT lead placement. Measurements revealed a trend toward greater SEAT thickness for the VIA compared to VVSP and VMS, suggesting a superior signal-to-noise-ratio in VVSP and VMS.

Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury

Background Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients. Methods Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value. Results Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks. Conclusions In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients.

Abstract 12874: Thebesian Veins Are Common and Progress in Adult Patients Late After Fontan Operation

Introduction: Thebesian veins (ThVs) are coronary veins that drain directly into the atrial or ventricular chamber. Angiographically detectable ThVs are a rare finding sometimes associated with myocardial ischemia due to coronary steal and volume overload of ventricles in adults. However, there are limited data concerning ThVs in the setting of congenital heart disease. The purpose of this study is to demonstrate presence, character, and changes with growth of ThVs in adult patients late after Fontan operation. Methods: This study is single-center retrospective review of adults with Fontan circulation patients who had undergone cardiac catheterization for routine Fontan surveillance between 2009-2019. We assessed the presence of angiographically detectable ThVs from ascending aortography. After identification of the characteristic cases, we examined the ventricular morphology, the portion of ThVs drainage, and compared with previous findings of angiograms. We also reviewed clinical manifestation and findings of exercise stress ECG of the patients. Pulmonary atresia with intact ventricular septum was excluded because abnormal coronary arterial communications have been well documented in this condition. Results: Among 75 Fontan patients who had undergone catheterization, significant ThVs were observed in a total of 12 cases (16%). There were 6 right-dominant single ventricle, 4 left-dominant single ventricle, and 2 unbalanced two ventricles. In all cases, including left-dominant single ventricle, all ThVs drained into right ventricle cavity, never into left ventricle. The patients who underwent serial catheterizations demonstrated that ThVs dilation and tortuosity progressed over time. Among 6 patients who had underwent exercise stress ECG, only 1 patient showed ST segment depression, however, none had clinical history of chest pain. Conclusions: ThVs are common and progress in adult patients late after Fontan operation. Although the clinical significance of these findings remains uncertain, particular attention should be given to myocardial ischemia and volume overload for the future of adult Fontan patients who have prominent ThVs.