Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis regulating the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of acute myocardial ischemia (AMI) rats. METHODS: Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups: Sham, AMI (Model), electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment (EA), non-acupoint electroacupuncture (Control), and Model + corticosterone (Model + CORT). AMI was induced occlusion of the left anterior descending coronary artery, followed by 3 d of electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment. In the Control group, electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail. The AMI + CORT group was injected with CORT (20 mg/kg) in saline. Hemorheology, electrocardiography (ECG), hematoxylin and eosin staining, and expression of glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP) were used to assess cardiac function. The effects of adrenocorticotropic hormone (ACTH) and CORT were evaluated by enzyme-linked immunosorbent assay. Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis. Protein expression was evaluated by Western blotting (vimentin and GFAP) and immunofluorescence staining (GFAP). RESULTS: Compared with the Sham group, the hemorheology indicators, heart rate, ECG-ST segment elevation, and GPBB and H-FABP levels were higher in Model rats. The EA group showed reductions in these indicators compared with the Model group. Similarly, in Model rats, the expression of ACTH and CORT were significantly increased compared with the Sham group. The EA group also showed reduced expression of ACTH and CORT. Importantly, proteomics analysis showed that vimentin was differentially expressed in Model rats. Compared with the Sham group, vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI + EA group. Additionally, intraperitoneal injection of CORT aggravated the expression of GPBB, H-FABP and GFAP. CONCLUSIONS: Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity, and that hippocampal GFAP may play an important role in the regulation.

Association between the diagnostic classification of newly diagnosed coronary artery disease and future heart failure development.

OBJECTIVE: The first clinical manifestation of coronary artery disease (CAD) varies widely from unheralded myocardial infarction (MI) to mild, incidentally detected disease. The primary objective of this study was to quantify the association between different initial CAD diagnostic classifications and future heart failure. METHODS: This retrospective study incorporated the electronic health record of a single integrated health care system. Newly diagnosed CAD was classified into a mutually exclusive hierarchy as MI, CAD with coronary artery bypass graft (CABG), CAD with percutaneous coronary intervention, CAD only, unstable angina, and stable angina. An acute CAD presentation was defined when the diagnosis was associated with a hospital admission. New heart failure was identified after the CAD diagnosis. RESULTS: Among 28 693 newly diagnosed CAD patients, initial presentation was acute in 47% and manifested as MI in 26%. Within 30 days of CAD diagnosis, MI [hazard ratio (HR) = 5.1; 95% confidence interval: 4.1-6.5] and unstable angina (3.2; 2.4-4.4) classifications were associated with the highest heart failure risk (compared to stable angina), as was acute presentation (2.9; 2.7-3.2). Among stable, heart failure-free CAD patients followed on average 7.4 years, initial MI (adjusted HR = 1.6; 1.4-1.7) and CAD with CABG (1.5; 1.2-1.8) were associated with higher long-term heart failure risk, but an initial acute presentation was not (1.0; 0.9-1.0). CONCLUSION: Nearly 50% of initial CAD diagnoses are associated with hospitalization, and these patients are at high risk of early heart failure. Among stable CAD patients, MI remained the diagnostic classification associated with the highest long-term heart failure risk, however, having an initial acute CAD presentation was not associated with long-term heart failure.

Impact of early ventricular tachycardia ablation in patients with an implantable cardioverter-defibrillator: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is limited information on whether early catheter ablation (CA) for ventricular tachycardia (VT) is associated with better outcomes compared with alternative strategies in patients with implantable cardioverter-defibrillator (ICD). OBJECTIVE: The purpose of this article was to assess the efficacy of early VT CA in patients with ICD. METHODS: EMBASE, PubMed, and Cochrane were searched from inception to April 2022. Randomized controlled trials comparing the efficacy of early VT CA with control groups, both in patients with ICD, were included in the analysis. Data on effect estimates in individual studies were extracted and combined via random effects meta-analysis using the DerSimonian and Laird method, a generic inverse variance strategy. RESULTS: Nine randomized controlled trials with 1106 patients (n = 1018, 92.1% with ischemic cardiomyopathy and n = 88, 7.9% with nonischemic cardiomyopathy) were evaluated. VT CA was associated with reduced VT recurrences (odds ratio [OR] 0.64; P = .007), appropriate ICD shocks (OR 0.53; P = .002), ICD therapies (OR 0.54; P = .002), and cardiovascular hospitalization (OR 0.67; P = .004). However, no significant differences were observed in terms of mortality rate, heart failure hospitalization, and quality of life between the early VT CA and control groups. CONCLUSION: Early CA was beneficial in reducing VT burden and ICD therapies. However, it did not affect mortality rate and quality of life. Since most patients in the included studies presented with ischemic cardiomyopathy, further studies on nonischemic cardiomyopathy should be conducted to validate if early CA has similar outcomes.

Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia.

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

Marjoram extract prevents ischemia reperfusion-induced myocardial damage and exerts anti-contractile effects in aorta segments of male wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marjoram (Origanum majorana L.) is an herb traditionally used as a medicine in different countries, as Morocco and Iran, because of its beneficial cardiovascular effects. Some studies suggest that these effects are due, at least in part, to the presence of phenolic compounds such as rosmarinic acid (RA) and luteolin. AIM OF THE STUDY: To analyze the possible cardiprotective effects of a marjoram extract (ME) reducing myocardial damage after coronary ischemia-reperfusion (IR) and its possible antihypertensive effects reducing the response of aorta segments to the vasoconstrictors noradrenaline (NA) and endothelin-1 (ET-1). MATERIALS AND METHODS: Male Wistar rats (300g) were used. After sacrifice, the heart was immediately removed and mounted in a perfusion system (Langendorff). The aorta was carefully dissected and cut in 2 mm segments to perform vascular reactivity experiments. RESULTS: In the heart, ME perfusion after IR reduced heart rate and prevented IR-induced decrease of cardiac contractility, possibly through vasodilation of coronary arteries and through the upregulation of antioxidant markers in the myocardium that led to reduced apoptosis of cardiomyocytes. In the aorta, ME decreased the vasoconstrictor response to NA and ET-1 and exerted a potent anti-inflammatory and antioxidant effect. Neither RA nor 6-hydroxi-luteolin-O-glucoside, major compounds of this ME, were effective in improving cardiac contractility after IR or attenuating vasoconstriction to NA and ET-1 in aorta segments. CONCLUSION: In conclusion, ME reduces the myocardial damage induced by IR and the contractile response to vasoconstrictors in the aorta. Thus, it may be useful for the treatment of cardiovascular diseases such as myocardial infarction and hypertension.

Uncovering the molecular mechanisms of Ilex pubescens against myocardial ischemia-reperfusion injury using network pharmacology analysis and experimental pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex pubescens (I. pubescens), has been widely used to treat cardiovascular disease (CVD) in South China. Several studies have revealed aspect of its phytochemistry and pharmacological activities in cardiovascular diseases, but its active compounds and mechanisms of action are still unclear. The aim of this study was to search for the active compounds and the pharmacological mechanisms of I. pubescens for myocardial ischemia-reperfusion injury (MI/RI) by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main targets of compounds in I. pubescens were predicted using the TargetNet webserver (http://targetnet.scbdd.com). The network between compounds and predicted targets related to MI/RI and compounds was constructed. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate I. pubescens targets acting on MI/RI, which were further validated by in vitro and in vivo experiments. RESULTS: A total of 191 targets were predicted for 64 chemical compounds in I. pubescens. Following Venn's analysis, we found that 38 candidate targets of I. pubescens were associated with protective effects against MI/RI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these targets were related to estrogen signaling pathway. Importantly, the cardioprotective effects of I. pubescens and its active compounds were evaluated and the regulatory effects on key targets of heat shock protein 90 alpha family class A member 1 (HSP90AA1) and Estrogen receptor 1 (ESRα) in estrogen signaling pathway were validated in vitro and in vivo. CONCLUSION: Our discoveries revealed that I. pubescens ameliorated MI/RI by regulating HSP90AA1 and ESRα in estrogen signaling pathway.

The Impact of Atrial Fibrillation on Outcomes of Peripheral Arterial Disease: Analysis of Routinely Collected Primary Care Data.

BACKGROUND: The combination of peripheral arterial disease and atrial fibrillation is linked with high risk of mortality and stroke. This study aims to investigate the impact of atrial fibrillation on patients with diagnosed peripheral arterial disease. METHODS: This is a retrospective study using The Health Improvement Network database, which contains prospectively collected data from participating primary care practices. Patients with a new diagnosis of peripheral arterial disease between January 8, 1995 and January 5, 2017 were identified in the database alongside relevant demographic information, clinical history, and medications. Every patient in the dataset with peripheral arterial disease and baseline atrial fibrillation (case) was matched to a patient without atrial fibrillation (control) with similar characteristics using propensity score matching. Cox-regression analysis was performed and hazard ratios (HR) calculated for the outcomes of death, stroke, ischemic heart disease, heart failure, and major amputation. RESULTS: Prevalence of atrial fibrillation in this cohort was 10.2%. All patients with peripheral arterial disease and atrial fibrillation (n = 5685) were matched with 5685 patients without atrial fibrillation but otherwise similar characteristics. After multivariate analysis, atrial fibrillation was independently associated with mortality (HR 1.18; 95% confidence interval [CI], 1.12-1.26; P < .01), cerebrovascular events (HR 1.35; 95% CI, 1.17-1.57; P < .01), and heart failure (HR 1.87; 95% CI, 1.62-2.15; P < .01), but not with ischemic heart disease or limb loss. CONCLUSION: In peripheral arterial disease patients, atrial fibrillation is a risk factor for mortality, stroke, and heart failure. This emphasizes the need for proactive surveillance and holistic management of these patients.

The effect of vitamin D supplementation on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Vitamin D might be beneficial in diabetic patients with ischemic heart disease through its favorable effect on metabolic profiles and biomarkers of inflammation and oxidative stress. We performed a protocol for systematic review and meta-analysis to assess whether vitamin D supplementation could improve glucose control and inflammation in type 2 diabetic patients with ischemic heart disease. METHODS: The proposed systematic review and meta-analysis will conform to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library were searched in October 2022 by 2 independent reviewers. The risk of bias assessment of the included studies was assessed using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). Data analysis was performed with Review Manager Software (RevMan Version 5.4, The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: This study will provide a high-quality synthesis to assess the effectiveness and safety of vitamin D supplementation on type 2 diabetic patients with ischemic heart disease. CONCLUSION: This systematic review may lead to several recommendations, for both patients and researchers, as which is the best therapy for type 2 diabetic patients with ischemic heart disease and how future studies need to be designed, considering what is available now and what is the reality of the patient.

Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia / 神经科学通报·英文版

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

Huoxin pill prevents acute myocardial ischaemia injury via inhibition of Wnt/ß-catenin signaling.

Myocardial infarction (MI) is one of the leading causes of death worldwide, and due to the widespread and irreversible damage caused, new therapeutic treatments are urgently needed in order to limit the degree of ischaemic damage following MI. Aberrant activation of Wnt/ß-catenin signalling pathway often occurs during cardiovascular diseases including MI, which results in excess production of reactive oxygen species (ROS) and further promotes myocardial dysfunction. Huoxin pill (HXP) is a Traditional Chinese Medicine formula that has been widely used in the treatment of coronary heart disease and angina; however, its mechanisms remain unclear. Here, we performed mouse models of MI and examined the effects and mechanisms of HXP in protecting against MI-induced ischaemic damage. Our study showed that administration with HXP robustly protected against MI-induced cardiac injuries, decreased infarct size and improved cardiac function. Moreover, HXP attenuated ischaemia-induced DNA damage occurrence in vivo and H2 O2 -induced DNA damage occurrence in vitro, via potent inhibition of adverse Wnt/ß-catenin signalling activation. Our study thus elucidated the role and mechanism of HXP in protecting against MI and oxidative stress-induced injuries and suggests new therapeutic strategies in ischaemic heart disease via inhibition of Wnt/ß-catenin signalling pathway.

Compound Danshen Dripping Pill ameliorates post ischemic myocardial inflammation through synergistically regulating MAPK, PI3K/AKT and PPAR signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Danshen Dripping Pill (CDDP), composed of Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H. Chen and Borneol, is a famous traditional Chinese medicine formula which has made great achievements in the treatment of ischemic heart disease, but the profound mechanism of CDDP improving post ischemic myocardial inflammation hasn't been clearly discussed. AIM OF THE STUDY: The aim of this study was to explore the biological mechanism of constituents in CDDP synergistically improving post ischemic myocardial inflammation. MATERIALS AND METHODS: The pharmacologic studies were applied to assess the cardio protection effect of CDDP in acute myocardial ischemic rats. To identify the anti-inflammatory ingredients in CDDP, an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with a dual-luciferase reporter assay for NF-κB inhibition were used. The network pharmacology and molecular docking assay were adopted to predict targets of anti-inflammatory ingredients and then the regulation effects of these active components on their targets were also verified. RESULTS: Our results indicated that CDDP exerted an excellent cardio protection effect by reversing echocardiographic abnormalities, attenuating histopathological lesion, ameliorating circulating myocardial markers and inflammation cytokines. Tanshinol, salvianolic acid B (Sal B), tanshinone IIA (Tan IIA) and notoginsenoside R1 (NGR1) were the pivotal anti-inflammatory ingredients in CDDP. The anti-inflammatory mechanism is that tanshinol and Sal B respectively targeted on PPARγ and JNK, while Tan IIA worked on AKT1 and NGR1 bound to PI3K. CONCLUSIONS: Our results firstly demonstrated that CDDP effectively ameliorated post ischemic myocardial inflammation through simultaneously modulating MAPK, PI3K/AKT and PPAR pathways in a multi-components synergetic manner.

Surgical Treatment of Ischemic Dilative Cardiomyopathy by Ventricular Restoration.

Patients with symptomatic post-ischemic dilative myocardiopathy of the left ventricle require, in selected cases, an operation to reshape and reduce the volume of the left ventricular chamber, in addition to surgical myocardial revascularization and mitral valve repair, with the aim of prolonging survival, improving the quality of life and minimizing the need for re-hospitalizations related to recurrent heart failure. This procedure is called surgical ventricular restoration (SVR), and is a useful tool for the treatment of heart failure patients as an alternative to heart transplant. This article provides an overview of surgical ventricular restoration for the treatment of dilative ischemic myocardiopathy. It illustrates several surgical options, describes the operative details, and discusses the correct indications for the procedure. Finally, an interesting protocol for one-step cell therapy during SVR is proposed, as an innovative treatment for heart failure patients.

Yixin-Shu Capsules Ameliorated Ischemia-Induced Heart Failure by Restoring Trx2 and Inhibiting JNK/p38 Activation.

Traditional Chinese medicine has shown great safety and efficacy in the treatment of heart failure (HF), whereas the mechanism remains unclear. In this study, the protective effect of Yixin-shu (YXS) capsules, a conventional medicine for various cardiovascular diseases, against myocardial ischemia-induced HF in rats was systematically investigated by RNA-seq technology. HF rats treated with YXS (0.8 or 1.6 g/kg/d, ig) for 6 weeks had significantly decreased brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and collagen III and attenuated cardiac structure rupture and collagen deposition. Additionally, YXS treatment decreased the levels of interleukin-1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) and TUNEL-positive rate and the nitrotyrosine staining, but increased levels of glutathione (GSH), total antioxidant capacity (T-AOC) activity, and mitochondrial membrane potential. Further experiments demonstrated that YXS restored Trx2 and inhibited the phosphorylation of JNK and p38, thereby improving cardiac function in the rats with HF. Silencing Trx2 decreased the protection of YXS in the response to H2O2 as evidenced by the increase of caspase-3 activity and decrease of GSH level. Thus, YXS enhanced heart function and decreased myocardial damage through restoring Trx2 and inhibiting JNK and p38 activation in ischemia-induced HF.

Decreased stroke risk with combined traditional Chinese and western medicine in patients with ischemic heart disease: A real-world evidence.

Both ischemic heart disease (IHD) and stroke are major causes of death worldwide. We investigated the effects of combined Traditional Chinese medicine (TCM) and western medicine (WM) on stroke risk in IHD patients.Taiwanese patients with IHD were enrolled in the TCM study during their outpatient visit. Stroke events after TCM or non-TCM treatment were examined. Chi-square tests and Student t-tests were used to examine differences between patients using and not using TCM. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs). Sex, age, and comorbidities were included in a multivariable Cox model to estimate the adjusted HR (aHR). The survival probability and the probability free of stroke were calculated by the Kaplan-Meier method.There were 733 IHD patients using TCM and 733 using non-TCM treatment, with the same proportion of sex and age within each cohort. Using single Chinese herb such as Dan Shen, San Qi, or Chuan Xiong would have lower stroke events and lower aHR than non-TCM in IHD patients. There was 0.3-fold lower stroke risk in IHD patients with combination TCM and non-TCM treatment (95% CI = 0.11-0.84, P = .02). Moreover, the survival rate was higher (P < .001) and the incidence of hemorrhagic stroke was significantly lower (P = .04) in IHD patients with TCM treatment.IHD patients using combined TCM and WM had a higher survival rate and lower risk of new onset stroke, especially hemorrhagic stroke than those who did not use TCM treatment.

Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis.

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

Direct Rivaroxaban-Induced Factor XA Inhibition Proves to be Cardioprotective in Rats.

BACKGROUND: Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear. Our study sought to evaluate the effect of rivaroxaban (RIV), a direct inhibitor of Factor Xa, on myocardial I/R injury and determine its cellular targets. EXPERIMENTAL APPROACH: We used a rat model of 40-min coronary ligation followed by reperfusion. RIV (3 mg/kg) was given per os 1 h before reperfusion. Infarct size and myocardial proteic expression of survival pathways were assessed at 120 and 30 min of reperfusion, respectively. Plasmatic levels of P-selectin and von Willebrand factor were measured at 60 min of reperfusion. Cellular RIV effects were assessed using hypoxia-reoxygenation (H/R) models on human umbilical vein endothelial cells and on rat cardiomyoblasts (H9c2 cell line). KEY RESULTS: RIV decreased infarct size by 21% (42.9% vs. 54.2% in RIV-treated rats and controls respectively, P < 0.05) at blood concentrations similar to human therapeutic (387.7 ±â€Š152.3 ng/mL) levels. RIV had no effect on H/R-induced modulation of endothelial phenotype, nor did it alter myocardial activation of reperfusion injury salvage kinase and survivor activating factor enhancement pathways at 30 min after reperfusion. However, RIV exerted a cytoprotective effect on H9c2 cells submitted to H/R. CONCLUSIONS: RIV decreased myocardial I/R injury in rats at concentrations similar to human therapeutic ones. This protection was not associated with endothelial phenotype modulation but rather with potential direct cytoprotection on cardiomyocytes.

Multisize Electrodes for Substrate Identification in Ischemic Cardiomyopathy: Validation by Integration of Whole Heart Histology.

OBJECTIVES: This study sought to evaluate the value of combined electrogram (EGM) information provided by simultaneous mapping using micro- and conventional electrodes in the identification of post-myocardial infarction ventricular tachycardia substrate. BACKGROUND: Ventricular tachycardias after myocardial infarction are related to scars with complex geometry. Scar delineation and ventricular tachycardia substrate identification relies on bipolar voltages (BV) and EGM characteristics. Early reperfusion therapy results in small, nontransmural scars, the details of which may not be delineated using 3.5 mm tip catheters. METHODS: Nine swine with early reperfusion myocardial infarction were mapped using Biosense Webster's QDOT Micro catheter, incorporating 3 microelectrodes at the tip of the standard 3.5 mm electrode. Analysis of EGM during sinus rhythm, right ventricular pacing, and short-coupled right ventricular extrastimuli was performed. The swine were sacrificed and mapping data were projected onto the heart. Transmural biopsies (n = 196) corresponding to mapping points were obtained, allowing a head-to-head comparison of EGM recorded by micro- and conventional electrodes with histology. RESULTS: To identify scar areas using standard electrodes, unique cutoff values of unipolar voltage <5.44 mV, BV <1.27 mV (conventional), and BV <2.84 mV (microelectrode) were identified. Combining the information provided by unipolar voltage and BV mapping, the sensitivity of scar identification was increased to 93%. Micro-EGM were better able to distinguish small near-fields corresponding to a layer of viable subendocardium than conventional EGM were. CONCLUSIONS: The combined information provided by multisize electrode mapping increases the sensitivity with which areas of scar are identified. EGM from microelectrodes, with narrower spacing, allow identification of near-fields arising from thin subendocardial layer and layers activated with short delay obscured in EGM from conventional mapping catheter.

Comparison of the Ventricular Tachycardia Circuit Between Patients With Ischemic and Nonischemic Cardiomyopathies: Detailed Characterization by Entrainment.

BACKGROUND: There has been increasing awareness of the 3-dimensional nature of ventricular tachycardia (VT) circuits. VT circuits in patients with ischemic cardiomyopathies (ICM) and non-ICM (NICM) may differ in this regard. METHODS: Among patients with structural heart disease and at least 1 hemodynamically tolerated VT undergoing ablation, we retrospectively analyzed responses to all entrainment maneuvers. RESULTS: Of 445 patients (ICM 228, NICM 217) undergoing VT ablation, detailed entrainment mapping of at least 1 tolerated VT was performed in 111 patients (ICM 71, NICM 40). Of 89 ICM VTs, the isthmus could be identified by endocardial entrainment in 55 (62%), compared with only 8 of 47 (17%) NICM VTs ( P<0.01). With combined endocardial and epicardial mapping, the isthmus could be identified in 56 (63%) ICM VTs and 12 (26%) NICM VTs ( P<0.01), whereas any critical component (defined as entrance, isthmus or exit) could be identified in 76 (85%) ICM VTs and 37 (79%) NICM VTs ( P=0.3). Complete success (no inducible VT at the end of ablation, 82% versus 65%, P=0.04) and 1-year, single-procedure VT-free survival (82% versus 55%, P<0.01) were both higher among patients with ICM. CONCLUSIONS: Among mappable ICM VTs, critical circuit components can usually be identified on the endocardium. In contrast, among mappable NICM VTs, although some critical component can typically be identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location.

Monophasic action potential amplitude for substrate mapping.

Although radiofrequency ablation has revolutionized the management of tachyarrhythmias, the rate of arrhythmia recurrence is a large drawback. Successful substrate identification is paramount to abolishing arrhythmia, and bipolar voltage electrogram's narrow field of view can be further reduced for increased sensitivity. In this report, we perform cardiac mapping with monophasic action potential (MAP) amplitude. We hypothesize that MAP amplitude (MAPA) will provide more accurate infarct sizes than other mapping modalities via increased sensitivity to distinguish healthy myocardium from scar tissue. Using the left coronary artery ligation Sprague-Dawley rat model of ischemic heart failure, we investigate the accuracy of in vivo ventricular epicardial maps derived from MAPA, MAP duration to 90% repolarization (MAPD90), unipolar voltage amplitude (UVA), and bipolar voltage amplitude (BVA) compared with gold standard histopathological measurement of infarct size. Numerical analysis reveals discrimination of healthy myocardium versus scar tissue using MAPD90 (P = 0.0158) and UVA (P < 0.001, n = 21). MAPA and BVA decreased between healthy and border tissue (P = 0.0218 and 0.0015, respectively) and border and scar tissue (P = 0.0037 and 0.0094, respectively). Contrary to our hypothesis, BVA mapping performed most accurately regarding quantifying infarct size. MAPA mapping may have high spatial resolution for myocardial tissue characterization but was quantitatively less accurate than other mapping methods at determining infarct size. BVA mapping's superior utility has been reinforced, supporting its use in translational research and clinical electrophysiology laboratories. MAPA may hold potential value for precisely distinguishing healthy myocardium, border zone, and scar tissue in diseases of disseminated fibrosis such as atrial fibrillation.NEW & NOTEWORTHY Monophasic action potential mapping in a clinically relevant model of heart failure with potential implications for atrial fibrillation management.