Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

The Pharmacologic Management of Cardiac Arrest.

The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of ß-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.

A case report of ventricular fibrillation following Shockwave intravascular lithotripsy during percutaneous coronary intervention.

BACKGROUND: Shockwave intravascular lithotripsy (S-IVL) is widely used during percutaneous coronary intervention (PCI) of calcified coronary arteries. Ventricular capture beats during S-IVL are common but arrhythmias are rare. CASE PRESENTATION: A 75-year-old woman was scheduled for PCI to a short, heavily calcified chronic total occlusion of the right coronary artery. After wiring of the occlusion, S-IVL was used to predilated the calcified stenosis. During S-IVL, the patient developed ventricular fibrillation twice. CONCLUSION: To our knowledge, this is only the second reported case of VF during S-IVL. Although very rare, it is important to be aware of this potential and serious complication.

A Case of Ventricular Fibrillation in Masked Long-QT Syndrome Coexisting with Coronary Vasospasm.

Although long-QT syndrome (LQTS) with a normal range QT interval at rest leads to fatal ventricular arrhythmias, it is difficult to diagnose. In this article, we present a rare case of a patient who suffered a cardiac arrest and was recently diagnosed with LQTS and coronary vasospasm. A 62-year-old man with no syncopal episodes had a cardiopulmonary arrest while running. During coronary angiography, vasospasm was induced and we prescribed coronary vasodilators, including calcium channel blockers. An exercise stress test was performed to evaluate the effect of medications and accidentally unveiled exercise-induced QT prolongation. He was diagnosed with LQTS based on diagnostic criteria. Pharmacotherapy and an implantable cardioverter defibrillator were used for his medical management. It is extremely rare for LQTS and coronary vasospasm to coexist. In cases of exercise-induced arrhythmic events, the exercise stress test might be helpful to diagnose underlying disease.

A proof-of-concept study evaluating cardiac compression techniques for cardiopulmonary resuscitation in laying hens (Gallus gallus).

OBJECTIVE: To determine in adult chickens which of 3 CPR techniques, sternal compressions (SC), SC with interposed caudal coelomic compressions (ICCC), or lateral compressions (LC), results in the highest mean systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) as measured directly from the carotid artery. DESIGN: Prospective, nonblinded, experimental crossover study. SETTING: University teaching hospital laboratory. ANIMALS: Ten retired laying hens. INTERVENTIONS: Birds were sedated, anesthetized, and placed in dorsal recumbency. A carotid artery catheter was placed to directly measure arterial pressure. Ventricular fibrillation was induced with direct cardiac stimulation using a 9-Volt battery. Each bird then received 2 minutes of the 3 different cardiac compression techniques in a random order by 3 different compressors, with the compressor order also randomized. Birds were subsequently administered IV epinephrine, and transthoracic defibrillation was attempted. At the end of experimentation, each bird was euthanized, and simple gross necropsies were performed. Linear mixed models followed by pairwise paired t-tests were performed to evaluate differences in pressures generated by each technique. MEASUREMENTS AND MAIN RESULTS: The primary study outcomes were SAP, DAP, and MAP over 2 minutes of compressions for each compression technique. Pressures from ICCC (SAP: 27.6 ± 5.3 mm Hg, DAP: 18.7 ± 5.2 mm Hg, MAP: 21.7 ± 5.2 mm Hg) were significantly higher than those from LC (SAP: 18.9 ± 5.4 mm Hg, DAP: 11.6 ± 4.1 mm Hg, MAP: 14.1 ± 4.5 mm Hg). Pressures from SC (SAP: 24.5 ± 6.4 mm Hg, DAP: 15.2 ± 4.3 mm Hg, MAP: 18.3 ± 5.0 mm Hg) were not significantly different from ICCC or LC. CONCLUSIONS: External compressions can generate detectable increases in arterial pressure in chickens with ventricular fibrillation. SC with ICCC generated significantly higher arterial pressures than LC. SC alone generated blood pressures that were not significantly different from those generated by SC with ICCC or LC.

Enhancing the accuracy of shock advisory algorithms in automated external defibrillators during ongoing cardiopulmonary resuscitation using a cascade of CNNEDs.

Delivery of continuous cardiopulmonary resuscitation (CPR) plays an important role in the out-of-hospital cardiac arrest (OHCA) survival rate. However, to prevent CPR artifacts being superimposed on ECG morphology data, currently available automated external defibrillators (AEDs) require pauses in CPR for accurate analysis heart rhythms. In this study, we propose a novel Convolutional Neural Network-based Encoder-Decoder (CNNED) structure with a shock advisory algorithm to improve the accuracy and reliability of shock versus non-shock decision-making without CPR pause in OHCA scenarios. Our approach employs a cascade of CNNEDs in conjunction with an AED shock advisory algorithm to process the ECG data for shock decisions. Initially, a CNNED trained on an equal number of shockable and non-shockable rhythms is used to filter the CPR-contaminated data. The resulting filtered signal is then fed into a second CNNED, which is trained on imbalanced data more tilted toward the specific rhythm being analyzed. A reliable shock versus non-shock decision is made when both classifiers from the cascade structure agree, while segments with conflicting classifications are labeled as indeterminate, indicating the need for additional segments to analyze. To evaluate our approach, we generated CPR-contaminated ECG data by combining clean ECG data with 52 CPR samples. We used clean ECG data from the CUDB, AFDB, SDDB, and VFDB databases, to which 52 CPR artifact cases were added, while a separate test set provided by the AED manufacturer Defibtech LLC was used for performance evaluation. The test set comprised 20,384 non-shockable CPR-contaminated segments from 392 subjects, as well as 3744 shockable CPR-contaminated samples from 41 subjects with coarse ventricular fibrillation (VF) and 31 subjects with rapid ventricular tachycardia (rapid VT). We observed improvements in rhythm analysis using our proposed cascading CNNED structure when compared to using a single CNNED structure. Specifically, the specificity of the proposed cascade of CNNED structure increased from 99.14% to 99.35% for normal sinus rhythm and from 96.45% to 97.22% for other non-shockable rhythms. Moreover, the sensitivity for shockable rhythm detection increased from 90.90% to 95.41% for ventricular fibrillation and from 82.26% to 87.66% for rapid ventricular tachycardia. These results meet the performance thresholds set by the American Heart Association and demonstrate the reliable and accurate analysis of heart rhythms during CPR using only ECG data without the need for CPR interruptions or a reference signal.

Analysis of the Association between Copy Number Variation and Ventricular Fibrillation in ST-Elevation Acute Myocardial Infarction.

Sudden cardiac death due to ventricular fibrillation (VF) during ST-elevation acute myocardial infarction (STEAMI) significantly contributes to cardiovascular-related deaths. Although VF has been linked to genetic factors, variations in copy number variation (CNV), a significant source of genetic variation, have remained largely unexplored in this context. To address this knowledge gap, this study performed whole exome sequencing analysis on a cohort of 39 patients with STEAMI who experienced VF, aiming to elucidate the role of CNVs in this pathology. The analysis revealed CNVs in the form of duplications in the PARP2 and TTC5 genes as well as CNVs in the form of deletions in the MUC15 and PPP6R1 genes, which could potentially serve as risk indicators for VF during STEAMI. The analysis also underscores notable CNVs with an average gene copy number equal to or greater than four in DEFB134, FCGR2C, GREM1, PARM1, SCG5, and UNC79 genes. These findings provide further insight into the role of CNVs in VF in the context of STEAMI.

Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Development of the NOCSAE Standard to Reduce the Risk of Commotio Cordis.

BACKGROUND: Commotio cordis, sudden cardiac death (SCD) caused by relatively innocent impact to the chest, is one of the leading causes of SCD in sports. Commercial chest protectors have not been demonstrated to mitigate the risk of these SCDs. METHODS: To develop a standard to assess chest protectors, 4 phases occurred. A physiological commotio cordis model was utilized to assess variables that predicted for SCD. Next, a surrogate model was developed based on data from the physiological model, and the attenuation in risk was assessed. In the third phase, this model was calibrated and validated. Finally, National Operating Committee on Standards for Athletic Equipment adopted the standard and had an open review process with revision of the standard over 3 years. RESULTS: Of all variables, impact force was the most robust at predicting SCD. Chest wall protectors which could reduce the force of impact to under thresholds were predicted to reduce the risk of SCD. The correlation between the experimental model and the mechanical surrogate ranged from 0.783 with a lacrosse ball at 30 mph to 0.898 with a baseball at 50 mph. The standard was licensed to National Operating Committee on Standards for Athletic Equipment which initially adopted the standard in January 2018, and finalized in July 2021. CONCLUSIONS: An effective mechanical surrogate based on physiological data from a well-established model of commotio cordis predicts the reduction in SCD with chest protectors. A greater reduction in force provides a great degree of protection from commotio cordis. This new National Operating Committee on Standards for Athletic Equipment standard for chest protectors should result in a significant reduction in the risk of commotio cordis on the playing field.

Multi-phase implementation of automated external defibrillator use by nurses during in-hospital cardiac arrest and its impact on survival.

OBJECTIVE: We sought to evaluate the impact of a medical directive allowing nurses to use defibrillators in automated external defibrillator-mode (AED) on in-hospital cardiac arrest (IHCA) outcomes. METHODS: We completed a health record review of consecutive IHCA for which resuscitation was attempted using a pragmatic multi-phase before-after cohort design. We report Utstein outcomes before (Jan.2012-Aug.2013;Control) the implementation of the AED medical directive following usual practice (Sept.2013-Aug.2016;Phase 1), and following the addition of a theory-based educational video (Sept.2016-Dec.2017;Phase 2). RESULTS: There were 753 IHCA with the following characteristics (Before n = 195; Phase 1n = 372; Phase 2n = 186): mean age 66, 60.0% male, 79.3% witnessed, 29.1% noncardiac-monitored medical ward, 23.9% cardiac cause, and initial ventricular fibrillation/tachycardia (VF/VT) 27.2%. Comparing the Before, Phase 1 and 2: an AED was used 0 time (0.0%), 21 times (5.7%), 15 times (8.1%); mean times to 1st analysis were 7 min, 3 min and 1 min (p < 0.0001); mean times to 1st shock were 12 min, 10 min and 8 min (p = 0.32); return of spontaneous circulation (ROSC) was 63.6%, 59.4% and 58.1% (p = 0.77); survival was 24.6%, 21.0% and 25.8% (p = 0.37). Among IHCA in VF/VT (n = 165), time to 1st analysis and 1st shock decreased by 5 min (p = 0.01) and 6 min (p = 0.23), and ROSC and survival increased by 3.0% (p = 0.80) and 15.6% (p = 0.31). There was no survival benefit overall (1.2%; p = 0.37) or within noncardiac-monitored areas (-7.2%; p = 0.24). CONCLUSIONS: The implementation of a medical directive allowing for AED use by nurses successfully improved key outcomes for IHCA victims, particularly following the theory-based education video and among the VF/VT group.

Asymptomatic children with ventricular pre-excitation/WPW pattern.

Paediatric patients with ventricular pre-excitation/asymptomatic WPW syndrome have a higher risk of atrial fibrillation degenerating into ventricular fibrillation and sudden cardiac death (SCD). In more than half of these patients this can be the first symptom presenting. Hence, it is important to conduct a risk stratification for SCD in asymptomatic patients with pre-excitation/delta wave in the ECGs. In this review, invasive risk stratification by electrophysiologic testing and ablation is recommended when possible. Catheter ablation is reported to have a high rate of success and low risk of complications.

Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.

Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.

Sex- and age-dependent susceptibility to ventricular arrhythmias in the rat heart ex vivo.

The incidence of life-threatening ventricular arrhythmias, the most common cause of sudden cardiac death (SCD), depends largely on the arrhythmic substrate that develops in the myocardium during the aging process. There is a large deficit of comparative studies on the development of this substrate in both sexes, with a particular paucity of studies in females. To identify the substrates of arrhythmia, fibrosis, cardiomyocyte hypertrophy, mitochondrial density, oxidative stress, antioxidant defense and intracellular Ca2+ signaling in isolated cardiomyocytes were measured in the hearts of 3- and 24-month-old female and male rats. Arrhythmia susceptibility was assessed in ex vivo perfused hearts after exposure to isoproterenol (ISO) and hydrogen peroxide (H2O2). The number of ventricular premature beats (PVBs), ventricular tachycardia (VT) and ventricular fibrillation (VF) episodes, as well as intrinsic heart rate, QRS and QT duration, were measured in ECG signals recorded from the surfaces of the beating hearts. After ISO administration, VT/VFs were formed only in the hearts of males, mainly older ones. In contrast, H2O2 led to VT/VF formation in the hearts of rats of both sexes but much more frequently in older males. We identified several components of the arrhythmia substrate that develop in the myocardium during the aging process, including high spontaneous ryanodine receptor activity in cardiomyocytes, fibrosis of varying severity in different layers of the myocardium (nonheterogenic fibrosis), and high levels of oxidative stress as measured by nitrated tyrosine levels. All of these elements appeared at a much greater intensity in male individuals during the aging process. On the other hand, in aging females, antioxidant defense at the level of H2O2 detoxification, measured as glutathione peroxidase expression, was weaker than that in males of the same age. We showed that sex has a significant effect on the development of an arrhythmic substrate during aging. This substrate determines the incidence of life-threatening ventricular arrhythmias in the presence of additional stimuli with proarrhythmic potential, such as catecholamine stimulation or oxidative stress, which are constant elements in the pathomechanism of most cardiovascular diseases.