Septal Coronary Artery Research Articles

Comprehensive approach and real-life patient registry: exploring management and patient outcomes in dealing with septal complications during left bundle branch area pacing

Abstract Background Left bundle branch area pacing (LBBAP) aims to capture the left bundle branch (LBB) through a transventricular septal approach. Pacing this left-sided conduction system requires deep septal lead positioning due to the subendocardial course of the LBB at the left-sided septum. Such deep septal lead deployment might cause iatrogenic septal complications and collateral damage to septal vasculature. Purpose This study aims to explore both the immediate and medium-term clinical results of septal complications during LBBAP in a large single-center patient cohort, while also entailing the management strategies employed to address these issues. Methods The LBBAP implant procedure was conducted using a lumen-less (LLL) or a stylet-driven pacing lead (SDL) and a dedicated delivery sheath. Septal complications encompassed septal perforations into the left ventricular cavity, septal coronary artery or venous fistulas (SCAF/SCVF) and septal hematomas, which were identified using fluoroscopy, echocardiography and electrocardiographic criteria. Enrollment included adult patients who required permanent pacing for bradycardia or heart failure indications in whom LBBAP was attempted between November 2019 and October 2023. Results The study enrolled 508 patients, with a mean age of 71±16 years and 60% male. Successful LBBAP was achieved in 471 (93%) patients. Septal complications during implant occurred in 24/508 patients (5%), including 19 cases of septal perforation (4%), 4 cases of SCAF (0.8%) and 1 case of SCVF (0.2%). All cases of septal perforation were identified during the implantation procedure and were effectively managed by lead retraction and septal repositioning, eventually resulting in successful LBBAP. With regard to SCAF and SCVF, all but one were detected via septography during implantation and were addressed by lead repositioning. One case of SCAF was detected the day after implant on post-procedural echocardiography and was conservatively managed without lead repositioning. No ventricular septal defects were observed on echocardiography, either immediately or during follow-up (mean follow-up period of 25±12 months). Septal kinetics remained unaffected on follow-up echocardiography (mean follow-up 23±9 months), and all SCAF cases healed spontaneously. Additionally, no septal hematomas were observed. Importantly, no late septal perforations occurred during the follow-up period. Furthermore, no cardiac ischemia or thoracic discomfort were reported among any of these patients. Conclusions The findings of this study underscore the safety of deep septal lead deployment in LBBAP, and highlight that LBBAP provides near physiologic pacing with a high success rate and a low incidence of septal complications. The majority of these complications are promptly detected during the implant procedure and often remain asymptomatic. Furthermore, they exhibit spontaneous healing without enduring persistent septal harm throughout the follow-up period.

Evaluation of coronary function in female rats with severe type 1 diabetes: Effects of combined treatment with insulin and pyridoxamine.

This study aimed to evaluate the coronary function, myocardium, and epicardial adipose tissue (EAT) in female rats with severe type 1 diabetes and the effects of combined treatment with insulin and pyridoxamine (AGEs inhibitor). Female Wistar rats were divided into groups: control (CTR, n=13), type 1 diabetes (DM1, n=12), type 1 diabetes treated with insulin (DM1+INS, n=11), and type 1 diabetes treated with insulin and pyridoxamine (DM1+INS+PDX, n=14). The vascular responsiveness was performed in the septal coronary artery and the protein expressions of AGE, RAGE, GPER, NF-kB was evaluated in the left ventricle (LV), as well as the reactive oxygen species (ROS) was measured in LV and in EAT. We analyzed plasma levels of glucose, estradiol, Nε-carboxymethylisine (CML), thiobarbituric acid reactive substances (TBARS), catalase (CAT), and superoxide dismutase (SOD). The maximal responses to ACh were reduced in the DM1 compared with the CTR group, accompanied by an increase in circulating glucose, CML, and TBARS. Additionally, the expression of NF-kB in LV and generation of ROS in the presence of MnTMPyP (SOD mimetic) were increased in the DM1 group compared with CTR. Only the combined treatment was effective for fully re-establish ACh relaxation response, NF-kB protein expression, ROS generation, and increased SOD activity in the DM1+INS+PDX group. The reduction of the endothelium-dependent relaxation response in the septal coronary artery of female rats with severe type 1 diabetes was normalized with the combined treatment with insulin and pyridoxamine, associated with reduced inflammation and oxidative stress in the myocardium and increased circulating antioxidant activity.

Initial experience of left bundle branch area pacing using stylet-driven pacing leads: A multicenter study.

Left bundle branch area pacing (LBBAP) has been performed exclusively using lumen-less pacing leads (LLL) with fixed helix design. This registry study explores the safety and feasibility of LBBAP using stylet-driven leads (SDL) with extendable helix design in a multicenter patient population. This study prospectively enrolled consecutive patients who underwent LBBAP for bradycardia pacing or heart failure indications at eight Belgian hospitals. LBBAP was attempted using SDL (Solia S60; Biotronik) delivered through dedicated delivery sheath (Selectra3D). Implant success, complications, procedural, and pacing characteristics were recorded at implant and follow-up. The study enrolled 353 patients (mean age 76 ± 39 years, 43% female). The mean number of implants per center was 25 (range: 5-162). Overall, LBBAP with SDL was successful in 334/353 (94%), varying from 93% to 100% among centers. Pacing response was labeled as left bundle branch pacing in 73%, whereas 27% were labeled as myocardial capture. Mean paced QRS duration and stimulus to left ventricular activation time measured 126 ± 21 ms and 74 ± 17. SDL-LBBAP resulted in low pacing thresholds (0.6 ± 0.4 V at 0.4 ms), which remained stable at 12 months follow-up (0.7 ± 0.3, p = .291). Lead revisions for SDL-LBBAP occurred in 5 (1.4%) patients occurred during a mean follow up of 9 ± 5 months. Five (1.4%) septal coronary artery fistulas and 8 (2%) septal perforations occurred, none of them causing persistent ventricular septal defects. The use of SDL to achieve LBBAP is safe and feasible, characterized by high implant success in low and high volume centers, low complication rates, and stable low pacing thresholds.

Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats.

Background:Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events.Aim:To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI.Methods:Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA.Results:MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples.Conclusions:Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.

Left bundle branch area pacing using stylet-driven pacing leads with a new delivery sheath: A comparison with lumen-less leads.

Left bundle branch area pacing (LBBAP) aims to achieve physiological pacing by capturing the conduction system in the area of the left bundle branch. LBBAP has exclusively been performed using lumen-less pacing leads (LLLs) with fixed helix design. This study explores the feasibility, safety, and pacing characteristics of LBBAP using stylet-driven leads (SDLs) with an extendable helix design. Patients, in which LBBAP was attempted for bradycardia or heart failure pacing indications, were prospectively enrolled at the Ghent University Hospital. LBBAP was attempted with two different systems: 1/LLL with fixed helix (SelectSecure 3830, MedtronicInc.) delivered through a preshaped sheath (C315His Medtronic Inc.) and 2/SDL with extendable helix (Solia S60, Biotronik, SE & CO) delivered through a new delivery sheath (Selectra 3D, Biotronik). The study enrolled 50 patients (mean age: 70 ± 14 years, 44% females). LBBAP with SDL was successful in 20/23 (87%) patients compared with 24/27 (89%) of patients in the LLL group (p = 0.834). Screw attempts, screw implant depth, procedural, and fluoroscopy times were comparable among both groups. Acute LBBAP thresholds were low and comparable between SDL and LLL (0.5 ± 0.15 V vs. 0.4 ± 0.17 V, p = 0.251). Pacing thresholds remained low at 3 ± 2.1 months of follow up in both groups and no lead revisions were necessary. Postprocedural echocardiography revealed a septal coronary artery fistula in one patient with SDLLBBAP. LBBAP using stylet-driven pacing leads is feasible and yields comparable implant success to LBBAP with LLLs. LBBAP thresholds are low and comparable with both types of leads.

P.35 TASK-1 Channels Play an Anticontractile Role in Rat Septal Coronary Artery Under Pharmacological Blockade of Endothelium

Purpose/Background/ObjectivesTASK-1 (TWIK-related acid-sensitive potassium) channels conduct background K+ currents in smooth muscle cells of pulmonary arteries suppressing vasocontraction. However, the vasomotor role of TASK-1 channels in systemic arteries as well as their regulation by the endothelium are poorly understood. Therefore, we investigated the impact of TASK-1 channels on the regulation of arterial contraction in the presence or absence of the relaxing influence of the endothelium in the brain and the heart, important regions of the systemic circulation.MethodsSegments of basilar and septal coronary arteries (2-mm long) were isolated from male Wistar rats and mounted in a wire myograph. The functional impact of TASK-1 channels was assessed by the effect of their blocker AVE1231 (1 µM) on contractile responses to the thromboxane A2 receptor agonist U46619. Experiments were performed first on endothelium-intact arteries and then after combined blockade of NO-synthase (L-NNA, 100 µM), cyclooxygenase (indomethacin, 10 µM) and EDHF (TRAM34, 1 µM and UCL1684, 0.1 µM).ResultsAVE1231 did not change basal tone and contractile responses to U46619 of either basilar or septal coronary arteries with intact endothelium. However, incubation with AVE1231 after pharmacological blockade of the endothelium led to the development of basal tone and augmented contractile responses to U46619 in septal coronary arteries, but not in basilar arteries.ConclusionsTASK-1 channels may play a protective anticontractile role in the coronary circulation under conditions of endothelial dysfunction.Supported by RSF (grant N 20-75-00027). We thank Sanofi for the gift of AVE1231.

Septal Coronary Artery Fistula Following Left Bundle Branch Area Pacing.

Left bundle branch area pacing (LBBAP) is a novel pacing technique that requires the pacing lead to be screwed through the septum toward the left side of the interventricular septum ([1][1]). An 84-year-old woman underwent LBBAP for third-degree atrioventricular block. LBBAP was performed with a 5.6

Modern mapping and ablation techniques to treat ventricular arrhythmias from the left ventricular summit and interventricular septum

Managing arrhythmias from the left ventricular summit and interventricular septum is a major challenge for the clinical electrophysiologist requiring intimate knowledge of cardiac anatomy, advanced training and expertise. Novel mapping and ablation strategies are needed to treat arrhythmias originating from these regions given the current suboptimal long-term success rates with standard techniques. Herein, we describe innovative approaches to improve acute and long-term clinical outcomes such as mapping and ablation using the septal coronary venous system and the septal coronary arteries, alcohol ablation, coil embolization, and ablation of all early sites among others.

Decreased inward rectifier and voltage-gated K+ currents of the right septal coronary artery smooth muscle cells in pulmonary arterial hypertensive rats.

In vascular smooth muscle, K+ channels, such as voltage-gated K+ channels (Kv), inward-rectifier K+ channels (Kir), and big-conductance Ca2+-activated K+ channels (BKCa), establish a hyperpolarized membrane potential and counterbalance the depolarizing vasoactive stimuli. Additionally, Kir mediates endothelium-dependent hyperpolarization and the active hyperemia response in various vessels, including the coronary artery. Pulmonary arterial hypertension (PAH) induces right ventricular hypertrophy (RVH), thereby elevating the risk of ischemia and right heart failure. Here, using the whole-cell patch-clamp technique, we compared Kv and Kir current densities (IKv and IKir) in the left (LCSMCs), right (RCSMCs), and septal branches of coronary smooth muscle cells (SCSMCs) from control and monocrotaline (MCT)-induced PAH rats exhibiting RVH. In control rats, (1) IKv was larger in RCSMCs than that in SCSMCs and LCSMCs, (2) IKv inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMCs, (3) IKir was smaller in SCSMCs than that in RCSMCs and LCSMCs, and (4) IBKCa did not differ between branches. Moreover, in PAH rats, IKir and IKv decreased in SCSMCs, but not in RCSMCs or LCSMCs, and IBKCa did not change in any of the branches. These results demonstrated that SCSMC-specific decreases in IKv and IKir occur in an MCT-induced PAH model, thereby offering insights into the potential pathophysiological implications of coronary blood flow regulation in right heart disease. Furthermore, the relatively smaller IKir in SCSMCs suggested a less effective vasodilatory response in the septal region to the moderate increase in extracellular K+ concentration under increased activity of the myocardium.

Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

Aim. The deficit of thyroid function is known to be accompanied by an increase in the overall peripheral vascular resistance. This work tested the hypothesis that long-term hypothyroidism leads to an increase in the vasoconstrictor effect of Rho-kinase in skeletal muscle and heart resistance arteries of adult rats.Materials and methods.Male Wistar rats consumed the antithyroid drug propylthiouracil (PTU) in drinking water (0.025%), starting at 10 weeks of age. The rats of the control group received PTU-free water. After 14 weeks, the contractile responses of the gastrocnemius muscle arteries (to the α1-adrenoceptor agonist methoxamine) and the septal coronary artery (to the thromboxane A2 receptor agonist U46619) were isometrically recorded. The contribution of the Rho-kinase to the arterial contractile responses was assessed using inhibitor Y27632 (3 μM).Results.The consumption of propylthiouracil was accompanied by a marked decrease of thyroid hormone concentrations and an increase in total cholesterol serum level as well as a decrease in body weight. Maximal contractile responses of studied arteries were also reduced in hypothyroid rats. However, basal tone and reactivity to the moderate concentrations of agonists in arteries of hypothyroid rats were increased compared to control animals. Y27632 significantly weakened the contractile responses of the arteries and negated the differences between the two groups of rats.Conclusion.Chronic hypothyroidism leads to an increase in the activity of the Rho-kinase signaling pathway in the arteries of the gastrocnemius muscle and heart, which results in the increase of the spontaneous tone of the arteries and their reactivity to agonists.

Intracardiac Echocardiography-Guided Device Closure of Non-PFO/ASD Shunts

ABSTRACTBackground: Intracardiac echocardiography (ICE) has been used during transcatheter closure of simple atrial level shunts, but its use in more complex shunt lesions has not been well described.Methods: We conducted a retrospective review of all cases of ICE use at Mayo Clinic from January 2002 to December 2013. We selected cases where ICE was used during closure of non-atrial septal defiects/patent foramen vale shunts. Data were collected about patient demographics, type and location of shunt, type of anesthesia used, use of additional imaging modalities, procedure duration, fluoroscopy time, type of device used, residual shunt at conclusion of the procedure, complications, and residual shunt at follow-up.Results: A total of 1521 procedures involving the use of ICE were performed during the study period. Thirteen patients (8 males, 61%) underwent 14 qualifying procedures. Median age at time of intervention was 54 (range 11–73) years; median weight was 73 (37–99) kg. The most common lesions were congenital or iatrogenic ventricular septal defect (n = 5, 38%), aorta-atrial shunt (n = 3, 23%), and coronary artery fistula (n = 2, 15%). Median procedure duration and fluoroscopy time were 133 (38–192) minutes and 34 (16–91) minutes, respectively. General anesthesia was used for only 4/14 procedures. There were no complications associated with ICE use. After a median follow-up duration of 47 (7–95) months, four patients had small residual shunts seen on echocardiography, only one of whom required repeat intervention.Conclusions: ICE may be helpful in directing transcatheter closure of complex intracardiac shunts. In most cases, ICE can be performed without the use of general anesthesia.

The arrangement of the coronary artery trunks is subject to inheritance factors: A study in Syrian hamsters.

The concept that anatomical variations in the coronary artery tree might be influenced by genes is relatively old. However, empirical evidence on the effect of genotype on the coronary morphology is still scarce. In the Syrian hamster, there is a septal coronary artery which arises from the left or from the right coronary artery and supplies most of the interventricular septum. The aim was to decide whether the anatomical origin of the septal artery is subject to inheritance factors. Overall, 483 internal casts of the heart and coronary arteries were examined. All the hamsters included in this study had normal coronary arteries. The results of 74 crosses were compared statistically to seek for any significant difference between the phenotypes of the offspring and the phenotypes of the parents. The left septal artery was over-represented in the offspring of crosses between parents having both a left septal artery (p<.01), while the right septal artery was over-represented in the offspring of crosses between parents, one with a right and the other with a left septal artery (p<.001), and, more markedly, in the offspring of crosses between parents both with a right septal artery (p<.001). These results are the first to reveal that the coronary artery pattern is influenced by genetic factors, at least in its proximal portion with regard to the aorta.

The role of echocardiography in the assessment of an iatrogenic coronary fistula

Abstract : We reported the case of a 61-year-old woman with a suspected postinfarction ventricular septal defect. The predominantly diastolic flow pattern at our echocardiographic assessment was inconsistent with this diagnosis. A computed tomography revealed a left anterior descending artery to right ventricle fistula. This case highlights the importance of echocardiographic assessment in the differential diagnosis between ventricular septal defect and coronary artery fistula.

Synchronisation between contrast media administration and caudocranial scan direction increases visualisation of altered coronary artery blood flow in patients presenting with dual left anterior descending coronary artery.

Coronary CT angiography (CCTA) has the advantage over invasive coronary angiography in that its non-invasive nature and minimal risk on patients. CCTA enables accurate assessment of the entire heart, coronary artery system and thorax, displaying three-dimensional information about the spatial relations of the anomalous vessels and surrounding intraluminal and extraluminal anatomy, and thereby contributing clinically important prognostic information. Dual left anterior descending (LAD) coronary artery consists of of two LAD arteries within the anterior interventricular sulcus (AIVS). Type 4 is infrequently reported subtype and differs from the others, with a long LAD originating from the right coronary artery (Mercado, A., Johnson Jr, G., Calver, D., & Sokol, R. J. (1989). Cocaine, pregnancy, and postpartum intracerebral hemorrhage. Obstetrics & Gynecology, 73(3, Part 2), 467-468. and the short LAD originating from the left main coronary artery. However, the radiological features between the short LAD and septal coronary arteries remain a controversy, with the latter being determined by CCTA. We present a case report based on short LAD terminating proximally in the AIVS and the long LAD originating from the RCA and terminating into the distal AIVS with the later having a long septal travelling parallel to the long LAD.

NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism

IntroductionThyroid hormones are essential for proper development of many systems and organs, including circulatory system. Thyroid deficiency during pregnancy may affect the cardiovascular function in children early on and later in adulthood. However, long-term effects of early thyroid deficiency are poorly understood. We hypothesized that antenatal/early postnatal hypothyroidism will influence anticontractile effect of NO in coronary arteries of adult rats. Design and methodsTo model antenatal/early postnatal hypothyroidism dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%, w/v) from the first day of pregnancy till 2 weeks after delivery. Control females were supplied with pure water. Their male offspring was grown up till the age of 10–12 weeks. Systolic blood pressure was measured using tail cuff method. Septal coronary arteries were isolated and studied in wire myograph. Blood serum thyroid hormones concentrations (ELISA) and NO metabolites level (Griess method) were evaluated. ResultsAt the age of 10–12 weeks thyroid hormones, TSH concentrations, NO metabolites and systolic blood pressure level didn't differ between groups. Arterial responses to acetylcholine and exogenous NO-donor DEA/NO were similar in control and PTU groups. Along with that, in control rats endothelium denudation strongly potentiated basal tone of arteries and their contractile responses to thromboxane A2 receptor agonist U46619. The effects of endothelium denudation were absent in PTU rats indicating that anticontractile effect of endothelium is abolished in their arteries. Further, NO-synthase inhibitor L-NNA (100 μM) caused significant elevation of basal tone and increased U46619-induced contraction of endothelium-intact arteries only in control rats, while had no effect in PTU group. ConclusionsOur data demonstrate that NO-mediated anticontractile effect of endothelium is eliminated in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. Therefore, maternal thyroid hormones deficiency may have detrimental consequences in adult offspring including coronary circulation pathologies, despite normal blood levels of thyroid hormones.

Restoration of ventricular septal hypoperfusion by cardiac resynchronization therapy in patients with permanent right ventricular pacing

BackgroundPacing from the right ventricular apex (RVA) is associated with cardiac dysfunction and shows electrophysiological features similar to left bundle branch block in which left ventricular (LV) mechanical dyssynchrony impairs septal coronary artery perfusion. MethodsA total of 62 non-ischemic patients with an implanted pacemaker at the RVA with a pacing rate of >95% were studied. LV septal coronary perfusion as indicated by the LV septal perfusion index was measured by electrocardiography (ECG)-gated single-photon emission computed tomography for all patients at baseline and for patients who were upgraded to CRT at 6months after CRT. Relationships among LV septal perfusion index, QRS duration, and LV ejection fraction were analyzed. ResultsAmong the patients with permanent RVA pacing, 28 of 62 (45%) had impaired septal perfusion (i.e., septal perfusion index <0.9). The LV septal perfusion index was significantly correlated with both QRS duration (r=−0.763, p<0.001) and LV ejection fraction (r=0.462, p=0.001). Eleven patients were upgraded to CRT. CRT significantly improved the LV septal perfusion index from 0.63 (SD=0.13) to 0.89 (SD=0.19) (p<0.001)and cardiac function: LV end-systolic volume from 102.3mL (SD=70.0) to 179.7mL (SD=118.4) (p=0.002) and LV ejection fraction from 22.5 (SD=8.9%) to 38.4% (SD=13.9%) (p=0.001). ConclusionsNearly half of the non-ischemic patients with permanent RVA pacing presenting with prolonged QRS duration and LV dysfunction developed LV septal hypoperfusion. Both septal perfusion and LV function improved in patients who were upgraded to CRT.

0542 : Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction

Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In the present study, the role of MR expressed in vascular smooth muscle cells (VSMC) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MRSMKO) and mice treated with the MR antagonist finerenone (MIfine) had improved left ventricular (LV) compliance and elastance when compared to infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, ml/mg/min: MI-CTL: 1.1±0.5, NS; MIMRSMKO: 4.6±1.6, P<0.05; MI-fine: 3.6±0.7, P<0.01). The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholineinduced NO-dependent relaxation, was also improved by MR deletion in VSMC or by finerenone treatment (relaxation %: MI-CTL: 36±5, MIMRSMKO: 54±3 and MI-fine: 76±4; P<0.05). Such impairment of the coronary endothelial function upon MI involved an oxidative-stress that was reduced when MR was deleted in VSMC or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from non-infarcted animals with low dose angiotensin-II (10-9mol/L) induced oxidative-stress and impaired acetylcholine-induced relaxation in CTL but neither in MRSMKO nor in mice pre-treated with finerenone. In conclusion, deletion of MR in VSMC improved LV dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects. The author hereby declares no conflict of interest

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction

Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In this study, the role of MR expressed in vascular smooth muscle cells (VSMCs) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, mL mg(-1) min(-1): MI-CTL: 1.1 ± 0.5, nonsignificant; MI-MR(SMKO): 4.6 ± 1.6 [P<0.05]; MI-fine: 3.6 ± 0.7 [P<0.01]). The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholine-induced nitric oxide-dependent relaxation, was also improved by MR deletion in VSMCs or by finerenone treatment (relaxation %: MI-CTL: 36 ± 5, MI-MR(SMKO): 54 ± 3, and MI-fine: 76 ± 4; P<0.05). Such impairment of the coronary endothelial function on MI involved an oxidative stress that was reduced when MR was deleted in VSMCs or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from noninfarcted animals with low-dose angiotensin-II (10(-9) mol/L) induced oxidative stress and impaired acetylcholine-induced relaxation in CTL but neither in MR(SMKO) nor in mice pretreated with finerenone. In conclusion, deletion of MR in VSMCs improved left ventricular dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects.

Enhanced nitric oxide bioavailability in coronary arteries prevents the onset of heart failure in rats with myocardial infarction

AimThe endothelium, mainly via nitric oxide (NO) release, adjusts the coronary flow. Cardiac function is closely linked to blood flow; thus, we tested the hypothesis that NO modulation in coronary arteries could be differentially adjusted after myocardial infarction (MI) in the presence or absence of heart failure (HF). Methods and resultsFour weeks after coronary occlusion, the infarcted rats were subdivided into rats without (MI) or with HF signs according to haemodynamic parameters. The septal coronary arteries were subsequently used to perform functional and molecular experiments. Acetylcholine (ACh)-induced relaxation was decreased in the coronary arteries following HF, whereas it was enhanced in the arteries of the MI compared with those of SHAM-operated (SO) rats. The relaxation induced by the NO donor was similar among the groups. NO production, which was evaluated by 4,5-diaminofluorescein diacetate, was reduced in the coronary arteries of the HF group and increased in the arteries with MI after ACh-induced stimulation. HF coronary arteries exhibited oxidative stress, which was evaluated via ethidium bromide-positive nuclei, whereas it was decreased in MI. To evaluate the mechanisms involved in the enhanced ACh-induced relaxation in the arteries following MI, certain septal coronary arteries were pre-incubated with L-NAME (a nonselective NO synthase (NOS) inhibitor), 7-NI (a selective neuronal NOS (nNOS) inhibitor) or LY294002 (a PI3-kinase inhibitor). L-NAME and LY294002 reduced ACh-induced relaxation in the MI and SO rats; however, these effects were greater in the MI arteries. 7-NI reduced only the ACh-relaxation in MI. In addition, the eNOS, nNOS, Akt, and superoxide dismutase isoform protein expressions were greater in the coronary arteries of the MI than in those of the SO groups. ConclusionOur data suggested that endothelial function was closely related to cardiac function after coronary occlusion. The coronary arteries from the HF rats exhibited reduced NO bioavailability, whereas the MI rats exhibited increased NO bioavailability because of increased eNOS/nNOS/PI3-kinase/Akt pathway and a reduction in ROS generation. These results suggest that enhanced NO modulation can prevent the onset of HF.

91 Intra-Cardiac Echocardiography (ICE) to Guide Alcohol Septal Ablation (ASA) in Hypertrophic Obstructive Cardiomyopathy (HOCM): A Prospective Comparison Study against Trans-Thoracic Echocardiography (TTE): Abstract 91 Table 1

<h3>Introduction</h3> Successful alcohol septal ablation (ASA) in hypertrophic obstructive cardiomyopathy (HOCM) reduces LVOT gradients. A third of patients do not respond; inaccurate location of the iatrogenic infarct can be responsible. Myocardial contrast studies following injection into a septal coronary artery guide ASA. Transthoracic echocardiography (TTE) is the current gold standard. TTE can be difficult in the lab environment. The ideal echocardiographic modality will see crucial anatomy relevant to ASA and delineate myocardial contrast well. We assessed ICE against TTE in ASA. <h3>Methods</h3> The ability of ICE and TTE to see relevant anatomy was assessed in two phases. Phase one recruited 25 successive patients undergoing PFO closure under ICE guidance. This was predominantly a feasibility study. Phase 2 recruited 20 successive HOCM patients undergoing ASA. The ability to assess myocardial contrast was assessed in phase 2. A scoring system to assess three key domains was used (see Table 1). Two independent experts scored paired, off-line TTE and ICE images, a score was allocated to each modality in each domain. <h3>Results</h3> Phase 1: ICE catheter manipulation to visualise the relevant anatomy was quick and safe. TTE was superior in viewing MV anatomy and SAM (score 1.4 vs. 0.4, p &lt; 0.0001) but ICE visualised the target septum better (1.66 vs 1.08; p &lt; 0.0001). There was no difference in ability to see adjacent structures. Phase 2: ICE was superior in viewing MV anatomy (1.88 vs 1.6; p = 0.02), superior catheter manipulation caused better scores in ICE. There was no difference in assessing target septum. TTE was superior in assessing adjacent structures (1.03 vs 0.63, p = 0.002). Myocardial Contrast injection was performed in 19/20 patients: ICE was able to visualise contrast satisfactorily in just 2/19. This was due to dense acoustic shadowing with inability to comment on surrounding myocardium (8/19), and inadequate opacification of the myocardium (6/19). Contrast localised to myocardium outside the field in 3/19 (RV cavity). This was not seen on ICE due to a narrower field of echo. TTE saw myocardial contrast location in all. <h3>Conclusions</h3> ICE cannot be used to guide ASA due to the inability to describe myocardial contrast distribution. ICE was better at seeing the motion of the MV, but TTE saw adjacent structures better. The ability of ICE to see SAM of the MV may lend itself to non-surgical septal reduction therapies that are not reliant on myocardial contrast.