Incidence Of Ventricular Fibrillation Research Articles

Blood cardioplegia reduces intraoperative ventricular fibrillation and transfusion requirements compared to crystalloid cardioplegia in canine mitral valve repair.

Cardioplegic solutions are indispensable for open-heart surgeries, including mitral valve repair (MVR), a potentially curative treatment for myxomatous mitral valve disease in dogs. However, procedural methodologies are not fully established, and complications are yet to be comprehensively understood. Cardioplegic solutions contain various substances to protect the myocardium under temporal cardiac arrest. Nevertheless, ventricular fibrillation (VF) occurs as a common complication after releasing the crossclamp. Based on these backgrounds, the search for optimal cardioplegic solutions in dogs undergoing MVR is an urgent issue. This study aims to evaluate the occurrence of VF in dogs treated with blood cardioplegia (BCP) versus crystalloid cardioplegia (CCP) during MVR. A total of 251 client-owned dogs who underwent MVR from November 2015 to November 2017 were included. We retrospectively assessed the relationship between VF and type of cardioplegia (CCP or BCP) based on surgical records, including VF incidence, transfusion use, crossclamp time, and echocardiographic measurements. Logistic regression analysis showed that the CCP group was associated with the occurrence of VF (OR, 2.378; CI, 1.133-4.992; P = .022). In addition, the CCP group was associated with transfusion use (OR, 2.586; CI, 1.232-5.428, P = .022). There was no difference between the groups for the pre- and postoperative echocardiographic measurements. The BCP group had a lower incidence of VF and less transfusion use than the CCP group. This finding indicates that BCP may be a superior cardioplegic technique for MVR in dogs.

Comparison of amiodarone and esmolol for prevention of reperfusion ventricular fibrillation in individuals undergoing heart valve or aortic surgery: a study protocol for a randomized controlled clinical trial

BackgroundAmiodarone and esmolol can help to prevent and treat post-cardiac surgery reperfusion ventricular fibrillation. However, the relative efficacies of these two drugs remain unknown. The aim of the current trial is to compare the performances of amiodarone and esmolol for preventing reperfusion ventricular fibrillation following open heart surgery.Methods/designThis is a single-center, prospective, double-blind, controlled clinical trial. A total of 260 patients undergoing heart valve or aortic surgery will be assigned randomly to treatment with prophylactic esmolol (intervention group) or amiodarone (control group). The main outcome is the incidence of reperfusion ventricular fibrillation following aortic opening during extracorporeal circulation. The secondary outcomes are the rate of automatic cardiac resuscitation, energy and frequency of electrical defibrillation, number of electrical defibrillations, and pacemaker use in the two groups of patients. Information on the patients’ general condition and the durations of anesthesia, extracorporeal circulation, aortic occlusion, and operation time will be recorded. We will also compare the heart rate, mean arterial pressure, and central venous pressure between the two groups of patients at induction of anesthesia (T1), start of surgery (T2), start of extracorporeal circulation (T3), aortic block (T4), aortic opening (T5), after opening for 10 (T6), 20 (T7), and 30 min (T8), at cessation of extracorporeal circulation (T9), and at the end of surgery (T10) and compare blood gas analysis results at T1, T5, T9, and T10.DiscussionThis study will determine if prophylactic esmolol is more effective than amiodarone for reducing the incidence of reperfusion ventricular fibrillation in patients undergoing heart valve or aortic surgery.Trial registrationChina Clinical Trials Registry ChiCTR1900026429. Registered on 2019.10.9.

Bupleurum exerts antiarrhythmic effects by inhibiting L-type calcium channels in mouse ventricular myocytes

BackgroundBupleurum (Bup), is a traditional effective medicine to treat colds and fevers in clinics. Multiple studies have demonstrated that Bup exhibites various biological activities, including cardioprotective effects, anti-inflammatory, anticancer, antipyretic, antimicrobial, and antiviral effects, etc. Currently, the effects of Bup on cardiac electrophysiology have not been reported yet. MethodsElectrocardiogram recordings were used to investigate the effects of Bup on aconitine-induced arrhythmias. Patch-clamp techniques were used to explore the effects of Bup on APs and ion currents. ResultsBup reduced the incidence of ventricular fibrillation (VF) and delayed the onset time of ventricular tachycardia (VT) in mice. Additionally, Bup (40 mg/mL) suppressed DADs induced by high-Ca2+ and shortened action potential duration at 50 % completion of repolarization (APD50) and action potential duration at 90 % completion of repolarization (APD90) to 60.89 % ± 8.40 % and 68.94 % ± 3.24 % of the control, respectively. Moreover, Bup inhibited L-type calcium currents (ICa.L) in a dose-dependent manner, with an IC50 value of 25.36 mg/mL. Furthermore, Bup affected the gated kinetics of L-type calcium channels by slowing down steady-state activation, accelerating the steady-state inactivation, and delaying the inactivation-recovery process. However, Bup had no effects on the Transient sodium current (INa.T), ATX II-increased late sodium current (INa.L), transient outward current (Ito), delayed rectifier potassium current (IK), or inward rectifier potassium current (IK1). ConclusionBup is an antiarrhythmic agent that may exert its antiarrhythmic effects by inhibiting L-type calcium channels.

Magnetic vagus nerve stimulation alleviates myocardial ischemia-reperfusion injury by the inhibition of pyroptosis through the M2AChR/OGDHL/ROS axis in rats.

Myocardial ischemia-reperfusion (I/R) injury is accompanied by an imbalance in the cardiac autonomic nervous system, characterized by over-activated sympathetic tone and reduced vagal nerve activity. In our preceding study, we pioneered the development of the magnetic vagus nerve stimulation (mVNS) system. This system showcased precise vagus nerve stimulation, demonstrating remarkable effectiveness and safety in treating myocardial infarction. However, it remains uncertain whether mVNS can mitigate myocardial I/R injury and its specific underlying mechanisms. In this study, we utilized a rat model of myocardial I/R injury to delve into the therapeutic potential of mVNS against this type of injury. Our findings revealed that mVNS treatment led to a reduction in myocardial infarct size, a decrease in ventricular fibrillation (VF) incidence and a curbing of inflammatory cytokine release. Mechanistically, mVNS demonstrated beneficial effects on myocardial I/R injury by inhibiting NLRP3-mediated pyroptosis through the M2AChR/OGDHL/ROS axis. Collectively, these outcomes highlight the promising potential of mVNS as a treatment strategy for myocardial I/R injury.

Effects of stellate ganglion block on the perioperative hemodynamics for coronary artery bypass grafting surgery

ABSTRACT Background Stellate ganglion block (SGB) is a successful technique that can potentially maintain hemodynamics and terminate fatal arrhythmia. We aimed to study the efficacy of SGB on hemodynamic changes after on pump coronary artery bypass grafting (CABG) surgery. Methods Forty patients who underwent CABG surgery at the Cardiac Surgical Academy Ain Shams University Hospital were randomly allocated to receive SGB or placebo between June 2020 and February 2021. After fulfilling the inclusion criteria, patients were classified as American Society of Anesthesiologists III and IV. Patients were randomly assigned to one of two groups utilizing a computer-generated block number in a sealed envelope. Group S (20 patients) received SGB, and Group C (20 patients) included matched controls who received a placebo solution in the SGB. Primary outcome was perioperative changes in heart rate and systolic and diastolic blood pressures. Secondary outcomes included the incidence of atrial and ventricular fibrillation, and myocardial ischemia in addition to the times from ICU admission to extubation, ICU stay, and hospital stay. Results A statistically substantial increase in systolic and diastolic blood pressure as well as increased incidence of AF and VF was found in the control group compared to the SGB group with p values <0.001, <0.001, 0.037, and 0.028, respectively. Conclusion SGB can reduce the hemodynamic responses to surgery and anesthesia, intraoperative tachyarrhythmias, and ICU and hospital stays.

Immediate, early and late ventricular fibrillation complicating acute myocardial infarction: insights from a real life registry

Abstract Background Conflicting data exist on the prognosis of ventricular fibrillation (VF) based on its timing in relation to coronary occlusion in acute myocardial infarction (AMI). Purpose To describe the patient profile and prognostic impact of VF during AMI according to its time of occurrence. Methods Data from three nationwide French cohorts carried out 5 years apart from 2005 to 2015 were analysed (FAST-MI program). All consecutive patients with AMI (STEMI and Non-STEMI) over a 1-month period were enrolled and followed 5 years. The present analysis focused on patients who presented with VF according to its time of occurrence defined as: immediate (out-of-hospital cardiac arrest), early (&amp;lt;48h at admission) and late (≥48h after admission). Results Out of 13 125 patients admitted for AMI (66±14 years, 71% men, 52% ST-elevation myocardial infarction-STEMI), 406 (3.1%) presented with VF including 205 immediate (50.5%), 147 early (36.2%) and 54 late (13.3%) VF episodes. Immediate and early VF were most frequent during STEMI (respectively 2.3% and 1.8% vs. 0.8% and 0.4% in non-STEMI, p&amp;lt;0.001), while late VF incidence was as frequent in ST-elevation and non-STEMI (0.5% vs 0.4%, p value). The proportion of immediate, early and late VF in AMI were similar in 2005, 2010 and 2015. Patients with immediate (61.6±13.2 yo) or early (62.4±14.2 yo) VF were younger than those with no VF (66.1±14.1 yo, p&amp;lt;0.001) while patients with late VF patients were the oldest (70.5±13.6 yo). LVEF was lower in patients with early (48±10%) or late (48±13%), compared with patients without VF (52±11%) or those with immediate VF (51±12%) (p&amp;lt;0.001). In-hospital mortality was particularly high in patients who developed immediate (24.9%) and late (37.0%) VF, intermediate in early VF patients (10.9%) and lowest in non-VF patients (3.0%) (p&amp;lt;0.001). Among patients alived at hospital discharge, and compared with patients with no VF (4.2%), the six-month mortality was considerably increased in the late VF subgroup (17.6%, adjusted HR: 6.04 [2.69-13.58], P&amp;lt;0.001), moderately increased in immediate VF (5.2%, HR:2.15 [1.06-4.34, P=0.03) ) and did not differ in early VF (1.5%, HR: 0.52 [0.13-2.11 P=0.36). At five years, mortality was also significantly higher in patients with late VF (38.2%, adjusted HR 1.72 [1.01-2.91]), with no significant difference between immediate, early, and non VF patients (14.2%, 11.5% and 19.3% respectively). Conclusions Patients with immediate, early and late VF during AMI do present with significantly different profiles. Still, only late VF (≥48h after admission) was associated with poorer outcome after the index hospitalisation, especially within the initial 6 months. By contrast with current guidelines based on relatively old data from the 2000s in secondary prevention in ischemic or non-ischemic settings, the extent to which patients with late VF would benefit from rapid cardioverter defibrillator implantation is questionable.3 months survival after VF in AMI5 year survival after VF in AMI

M6A methyltransferase METTL3 contributes to sympathetic hyperactivity post-MI via promoting TRAF6-dependent mitochondrial ROS production

ObjectivesN6-methyladenosine (m6A) is the most prevalent post-translational modification in eukaryotic mRNA. Recently, m6A editing modified by methyltransferase-like enzyme 3 (METTL3), the core m6A methyltransferase, has been demonstrated to be involved in cardiac sympathetic hyperactivity. This study aimed to clarify the effects and underlying mechanisms of METTL3 in the paraventricular nucleus (PVN) in mediating sympathetic activity following myocardial infarction (MI). MethodsWe established rat MI models by left anterior descending coronary artery ligation. m6A quantification was performed.The expression of METTL3 and its downstream gene, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), were determined. The functional role of METTL3 in sympathetic hyperactivity and electrical conduction stability were verified by assessing renal sympathetic nerve activity (RSNA), norepinephrine (NE) levels, and programmed electrical stimulation. Rescue experiments were also conducted. The mechanism by which m6A is involved in mitochondrial reactive oxygen species (mROS) production, mediated by TRAF6/ECSIT pathway, was explored in lipopolysaccharide (LPS) treated primary microglial cells. ResultsMETTL3 was predominantly localized in the microglia and significantly increased within the PVN at 3 days post-MI. Inhibition of METTL3 decreased m6A levels, TRAF6 expression, and mROS production; downregulated sympathoexcitation, indicated by attenuated NE concentration and RSNA; decreased the incidence of ventricular tachycardia or fibrillation; and improved cardiac function. Mechanistically, downregulation of METTL3 prevented TRAF6 translocation to the mitochondria in the microglia and subsequent TRAF6/ECSIT pathway activation, resulting in decreased mROS production. ConclusionsThis study demonstrates that METTL3-mediated m6A modification promotes sympathetic hyperactivity through TRAF6/ECSIT pathway and mitochondrial oxidative stress in the PVN, thereby leading to ventricular arrhythmias post-MI.

Outcomes of hypothalamic oxytocin neuron-driven cardioprotection after acute myocardial infarction

Altered autonomic balance is a hallmark of numerous cardiovascular diseases, including myocardial infarction (MI). Although device-based vagal stimulation is cardioprotective during chronic disease, a non-invasive approach to selectively stimulate the cardiac parasympathetic system immediately after an infarction does not exist and is desperately needed. Cardiac vagal neurons (CVNs) in the brainstem receive powerful excitation from a population of neurons in the paraventricular nucleus (PVN) of the hypothalamus that co-release oxytocin (OXT) and glutamate to excite CVNs. We tested if chemogenetic activation of PVN-OXT neurons following MI would be cardioprotective. The PVN of neonatal rats was transfected with vectors to selectively express DREADDs within OXT neurons. At 6 weeks of age, an MI was induced and DREADDs were activated with clozapine-N-oxide. Seven days following MI, patch-clamp electrophysiology confirmed the augmented excitatory neurotransmission from PVN-OXT neurons to downstream nuclei critical for parasympathetic activity with treatment (43.7 ± 10 vs 86.9 ± 9 pA; MI vs. treatment), resulting in stark improvements in survival (85% vs. 95%; MI vs. treatment), inflammation, fibrosis assessed by trichrome blue staining, mitochondrial function assessed by Seahorse assays, and reduced incidence of arrhythmias (50% vs. 10% cumulative incidence of ventricular fibrillation; MI vs. treatment). Myocardial transcriptomic analysis provided molecular insight into potential cardioprotective mechanisms, which revealed the preservation of beneficial signaling pathways, including muscarinic receptor activation, in treated animals. These comprehensive results demonstrate that the PVN-OXT network could be a promising therapeutic target to quickly activate beneficial parasympathetic-mediated cellular pathways within the heart during the early stages of infarction.

Intense Caloric Restriction from Birth Prevents Cardiovascular Aging in Rats.

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

Naringin exerts antiarrhythmic effects by inhibiting channel currents in mouse cardiomyocytes.

Naringin, a flavonoid extracted from citrus plants, has a variety of biological effects. Studies have shown that increasing the consumption of flavonoid-rich foods can reduce the incidence of cardiac arrhythmia. Naringin has been reported to have beneficial cardiovascular effects and thus can be used to prevent cardiovascular diseases, but the electrophysiological mechanism through which it prevents arrhythmias has not been elucidated. This study was conducted to investigate the effect of naringin on the transmembrane ion channel currents in mouse ventricular myocytes and the antiarrhythmic effect of this compound on Langendorff-perfused mouse hearts. Action potentials (APs) and ionic currents were recorded in isolated ventricular myocytes using the whole-cell patch-clamp technique. Anemone toxin II (ATX II) and CaCl2 were used to induce early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively. Electrocardiogram (ECG) recordings were conducted in Langendorff-perfused mouse hearts with a BL-420F biological signal acquisition and analysis system. At the cellular level, naringin shortened the action potential duration (APD) of ventricular myocytes and decreased the maximum depolarization velocity (Vmax) of APs.Naringin inhibited the L-type calcium current (ICa.L) and ATX II enhanced the late sodium current (INa.L) in a concentration-dependent manner with IC50 values of 508.5μmol/L (n=9) and 311.6μmol/L (n=10), respectively. In addition, naringin also inhibited the peak sodium current (INa·P) and delayed the rectifier potassium current (IK) and the transient outward potassium current (Ito). Moreover, naringin reduced ATX II-induced APD prolongation and EADs and had a significant inhibitory effect on CaCl2-induced DADs as well. At the organ level, naringin reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by ATX II and shortened the duration of both in isolated hearts. Naringin can inhibit the occurrence of EADs and DADs at the cellular level; furthermore, it can inhibit INa.L, ICa.L, INa·P, IK, and Ito in ventricular myocytes. Naringin also inhibits arrhythmias induced by ATX II in hearts. By investigating naringin with this electrophysiological method for the first time, we determined that this flavonoid may be a multichannel blocker with antiarrhythmic effects.

Phloretin ameliorates heart function after myocardial infarction via NLRP3/Caspase-1/IL-1β signaling

Objectives/AimsInflammation is crucial in structural and electrical remodeling after myocardial infarction (MI), affecting cardiac pump function and conduction pathways. Phloretin possesses an anti-inflammation role by inhibiting the NLRP3/Caspase-1/IL-1β pathway. However, the effects of Phloretin on cardiac contractile and electrical conduction function after MI remained unclear. Therefore, we aimed to investigate the potential role of Phloretin in a rat model of MI. MethodsRats were assigned into four groups: Sham, Sham+Phloretin, MI and MI+Phloretin, with ad libitum food and water. In the MI and MI+Phloretin groups, the left anterior descending coronary artery was occluded for 4 weeks, while the Sham and Sham+Phloretin groups received sham operation. The Sham+Phloretin group and the MI+Phloretin group received oral administration of Phloretin. In vitro, H9c2 cells were subjected to hypoxic conditions to simulate an MI model, with Phloretin for 24 h. Cardiac electrophysiological properties were assessed following MI, including the effective refractory period (ERP), action potential duration (APD)90 and ventricular fibrillation (VF) incidence. Echocardiography evaluated left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), left ventricular internal diameter at end-diastole (LVIDd), left ventricular internal diameter at end-systole (LVIDs), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) to assess cardiac function. Serum type B natriuretic peptide (BNP) level was applied to evaluate the degree of Heart failure (HF). The fibrosis area and severity were assessed by Masson staining and protein expression levels of collagen 3, collagen 1, TGF-β and α-SMA. Western blot analysis estimated the protein expression levels of NLRP3, Pro Caspase-1, Caspase-1, ASC, IL-18, IL-1β, pp38, p38, and Connexin43(Cx43) to elucidate the influence of inflammation on electrical remodeling after MI. ResultsOur findings demonstrate that Phloretin inhibits the NLRP3/Caspase-1/IL-1β pathway, leading to the upregulation of Cx43 by limiting p38 phosphorylation, which further decreases susceptibility to ventricular arrhythmias (VAs). Additionally, Phloretin attenuated fibrosis by inhibiting inflammation to prevent HF. In vitro experiments also provided strong evidence supporting the inhibitory effects of Phloretin on the NLRP3/Caspase-1/IL-1β pathway. ConclusionOur results suggest that Phloretin could suppress the NLRP3/Caspase-1/IL-1β pathway to reverse structural and electrical remodeling after MI to prevent the occurrence of VAs and HF.

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury.

Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

In Hospital Outcome of Patients with Acute St-Elevation Myocardial Infarction Requiring Temporary Pacemaker

Background and Aim: Acute myocardial infarction is a serious public health concern around the globe and temporary pacing is required in a variety of myocardial infarction. The present study aimed to determine the in-hospital outcome of acute ST elevation myocardial infarction patients requiring a temporary pacemaker. Patients and Methods: This descriptive cross-sectional study was carried out on 120 acute myocardial infarction patients in the Cardiology Unit of PIMS Hospital, Islamabad from January 2021 to March 2023. Each individual underwent chest X-ray, ECG and serum markers. A detailed physical history including age, gender, smoking history, occupation, ischemic heart disease, diabetes, and hypertension were noted in specific designed proforma. Inclusion Criteria: Acute myocardial infarction patients who had chest pain, elevated serum markers, New onset ST Elevation and complete heart block on ECG and required pace maker during their hospitalization were enrolled. Exclusion Crieteria: Complete Heart block due to CKD or electrolyte imbalance, beta blocker or calcium channel blocker overdose, congenital heart block were excluded from the study. Results: The overall mean age was 52.64±6.8 years. The incidence of smokers, diabetes, and hypertension was 76 (63.3%), 56 (46.7%), and 52 (43.3%) respectively. The mean duration of symptom’s onset during hospital admission was 7.9±3.8 hours. About 48 (40%) patients had implanted temporary pacemaker at presentation, 66 (55%) on first post MI day, and 6 (5%) on 2nd post MI day. The in-hospital mortality was 8.3% (n=10). The incidence of ventricular tachycardia, ventricular fibrillation, and asystole was 28.3% (n=34), 3.3% (n=4) and 1.7% (n=2) respectively. Conclusion: The present study found that complete heart block is associated with a poorer early prognosis in individuals with ST-Elevation MI who require temporary pacemaker. In these individuals, a more intensive therapy strategy targeted at reducing early death is required. Keywords: Acute myocardial infarction, in-hospital outcome, temporary pace maker

Age and genetics are associated with ventricular fibrillation but not with monomorphic ventricular tachycardia in Brugada syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction Brugada syndrome (BrS) is associated with ventricular arrhythmias (VA) in macroscopically normal hearts. VA in BrS can be classified as ventricular fibrillation (VF) and monomorphic ventricular tachycardia (MVT). Although BrS has been initially described in association with VF, MVT is not rare, as it occurs in ≈30% of BrS patients. Purpose The aim of this study is to correlate VF or MVT with the genetic background and other clinical variables. Methods All BrS patients, were prospectively enrolled in a monocentric registry between 1992 and 2022. Inclusion criteria for the study were: 1) BrS diagnosis; 2) Genetic analysis performed for SCN5A; 3) Classification of variants following ACMG guidelines. Patients with a pathogenic/likely pathogenic (P/LP) variant in SCN5A were defined as (P+). Patients without a P/LP variant were defined as (P-). Primary endpoint was VA occurrence, defined as: documented arrhythmic SCD, documented arrhythmic aborted SCD, VF, sustained MVT or appropriate ICD intervention. All VA events were adjudicated as VF or MVT. Results A total of 500 BrS patients were analyzed. A P/LP variant in SCN5A was found in 104 patients (20.8%). After a mean follow-up of 110.9 months, 48 patients (9.6%) experienced a VA, adjudicated as MVT in 18 patients (37.5%) and VF in 30 patients (62.5%). At survival analysis, P- patients had higher VF free survival, compared with P+ patients (96.5% vs 84.6%, Log-Rank p&amp;lt;0.001) with no difference in MVT free survival (Log-Rank p=0.61), Figure 1. BrS patients &amp;gt; 30 years at diagnosis had higher VF free survival, compared with patients ≤ 30 years at diagnosis (95.5% vs 90.3%, Log-Rank p=0.041), with no difference in MVT free survival (Log-Rank p=0.9), Figure 2. Patients &amp;gt; 50 years at index event had higher VF free survival, compared with patients ≤ 50 years at index event (Log-Rank p=0.002), with no significant difference in MVT free survival (Log-Rank p=0.81). At Cox multivariate analysis independent predictors of VF occurrence were as follows: Age at index event ≤ 50 years (HR=2.57, CI 95% 1.01-6.6, p=0.04), P/LP variant in SCN5A (HR= 2.35, CI 95% 1.12-4.92, p=0.02), SND (HR= 2.67, CI 95% 1.01-7.04, p=0.044), history of syncope (HR= 2.14, CI 95% 1.02-4.51, p=0.047) and history of aborted SCD (HR= 18.66, CI 95% 8.87-39.27, p&amp;lt;0.001). Independent predictors of MVT occurrence were the following: history of syncope (HR= 2.71, CI 95% 1.26-5.80, p=0.01), history of aborted SCD (HR= 4.82, CI 95% 2.14-10.85, p&amp;lt;0.001), VA inducibility at EPS (HR= 3.71, CI 95% 1.66-8.31, p=0.001). Conclusion In a large BrS cohort undergoing genetic analysis MVT occurred in 37.5% of patients and VF in 62.5% of patients. P/LP SCN5A carriers and younger BrS population had a higher incidence of VF with no difference in MVT incidence.

A prediction model for ventricular arrythmias in the acute phase of infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in the acute phase of infarction (first 24-48 hours) has declined over recent decades, probably due to the uptake of reperfusion strategies and the early use of beta-blockers. However, according to some series, 6–8% of patients still develop hemodynamically significant VT or VF during this phase. Purpose The objective of our study was to evaluate the baseline characteristics of patients who suffered VT or VF in the acute phase of the infarction and to create a predictive model of ventricular arrhythmias in this setting which allow us to anticipate arrhythmic events. Methods We performed an observational, retrospective, and single-centre study carried out through the review of clinical records of patients who suffered an acute myocardial infarction with ST-segment elevation (STEMI) and were admitted in our Coronary Care Unit between July 2011 and August 2022. Results In our cohort we observed 179 episodes of VT/VF (10,7%) in a population of 1668 patients underwent STEMI. The mean age in this subgroup was 61,69±12,61 years old, 78% were males and 56% smokers. Approximately a quarter of the patients were diabetic or obese. There was a very low percentage of previous myocardial infarction (12%) and heart failure (3%) (Table 1). We estimated the best prediction model (Mallows’ Cp=5.12) for VT/VF. The variables included in our model (LL=-435,43) were: male sex, absence of diabetes, smoking habit, use of fibrinolysis, worst Killip at admission and hypotension at admission (Table 2). Conclusion The presence of VT or VF in the acute phase of infarction is still considered a controversial factor in the prognosis of these patients. In our cohort we identified that males, smokers, non-diabetics, and the use of fibrinolysis and the worst haemodynamical situation at admission were independent predictors of developing VT/VF in this context.

Reperfusion-induced injury and the effects of the dithioacetate type hydrogen sulfide donor ibuprofen derivative, BM-88, in isolated rat hearts

Hydrogen sulfide (H2S) plays an important role in cardiac protection by regulating various redox signalings associated with myocardial ischemia/reperfusion (I/R) induced injury. The goal of the present investigations is the synthesis of a newly designed H2S-releasing ibuprofen derivative, BM-88, and its pharmacological characterization regarding the cardioprotective effects in isolated rat hearts. Cytotoxicity of BM-88 was also estimated in H9c2 cells. H2S-release was measured by an H2S sensor from the coronary perfusate. Increasing concentrations of BM-88 (1.0 to 20.0 µM) were tested in vitro studies. Preadministration of 10 µM BM-88 significantly reduced the incidence of reperfusion-induced ventricular fibrillation (VF) from its drug-free control value of 92% to 12%. However, no clear dose dependent reduction in the incidence of reperfusion-induced VF was observed while different concentrations of BM-88 were used. It was also found that 10 µM BM-88 provided a substantial protection and significantly reduced the infarct size in the ischemic/reperfused myocardium. However, this cardiac protection was not reflected in any significant changes in coronary flow and heart rates. The results support the fact that H2S release plays an important role mitigating reperfusion-induced cardiac damage.

Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia.

Background Cardiac adrenergic receptor gene polymorphisms have the potential to influence risk of developing ventricular fibrillation (VF) during ST-segment-elevation myocardial infarction, but no previous study has comprehensively investigated those most likely to alter norepinephrine release, signal transduction, or biased signaling. Methods and Results In a case-control study, we recruited 953 patients with ST-segment-elevation myocardial infarction without previous cardiac history, 477 with primary VF, and 476 controls without VF, and genotyped them for ADRB1 Arg389Gly and Ser49Gly, ADRB2 Gln27Glu and Gly16Arg, and ADRA2C Ins322-325Del. Within each minor allele-containing genotype, haplotype, or 2-genotype combination, patients with incident VF were compared with non-VF controls by odds ratios (OR) of variant frequencies referenced against major allele homozygotes. Of 156 investigated genetic constructs, 19 (12.2%) exhibited significantly (P<0.05) reduced association with incident VF, and none was associated with increased VF risk except for ADRB1 Gly389 homozygotes in the subset of patients not receiving β-blockers. ADRB1 Gly49 carriers (prevalence 23.0%) had an OR (95% CI) of 0.70 (0.49-0.98), and the ADRA2C 322-325 deletion (Del) carriers (prevalence 13.5%) had an OR of 0.61 (0.39-0.94). When present in genotype combinations (8 each), both ADRB1 Gly49 carriers (OR, 0.67 [0.56-0.80]) and ADRA2C Del carriers (OR, 0.57 [0.45- 0.71]) were associated with reduced VF risk. Conclusions In ST-segment-elevation myocardial infarction, the adrenergic receptor minor alleles ADRB1 Gly49, whose encoded receptor undergoes enhanced agonist-mediated internalization and β-arrestin interactions leading to cardioprotective biased signaling, and ADRA2C Del322-325, whose receptor causes disinhibition of norepinephrine release, are associated with a lower incidence of VF. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT00859300.

Potential use of prophylactic intracoronary atropine in reducing reperfusion vagal reflex-related events in ST-elevation myocardial infarction

In this study, we evaluated the potential use of atropine in reducing reperfusion vagal reflex-related events during emergency percutaneous coronary intervention (PCI) for acute inferior ST-elevation myocardial infarction (STEMI). Retrospectively, we included 142 patients with inferior wall STEMI, who were treated between October 2015 and October 2020, in this study. The patients were divided into an experimental group (n = 70) and a control group (n = 72) depending on whether they received prophylactic intracoronary atropine. The experimental group was then subdivided into a low-dose group (0.5 – 1 mg atropine, n = 40) and a high-dose group (2 mg atropine, n = 30). We compared the incidence of reperfusion vagal reflex-related events and the application of temporary pacemakers between these groups. The results showed that the incidence of bradycardia (24.3% vs. 45.8%, P = 0.007), hypotension (18.6% vs. 40.3%, P = 0.005), ventricular tachycardia (4.3% vs. 19.4%, P = 0.005), and ventricular fibrillation (8.6% vs. 20.8%, P = 0.040) as well as the application of temporary pacemakers (14.3% vs. 29.2%, P = 0.032) were all much lower (all P &lt; 0.05) in the experimental group than in the control group. In addition, the incidence of bradycardia (10% vs. 35%, P = 0.016), hypotension (6.7% vs. 27.5%, P = 0.027), ventricular tachycardia (6.7% vs. 25%, P = 0.044), and ventricular fibrillation (0 vs. 15%, P = 0.034) as well as the application of temporary pacemakers (3.3% vs. 22.5%, P = 0.036) were all much lower (all P &lt; 0.05) in the high-dose group than the low-dose group. Our findings demonstrate that atropine pretreatment could prevent reperfusion vagal reflex-related events and reduce the application of temporary pacemakers during emergency PCI for acute inferior STEMI. These effects can be significantly enhanced by high-dose (2 mg) atropine pretreatment.

Dietary Canola Oil Modifies Myocardial Fatty Acids and Inhibits Cardiac Arrhythmias in Rats

Previous research showed that dietary fish oil was potently antiarrhythmic in rats but olive oil was not. This study was designed to test the hypothesis that canola oil, another major dietary source of oleic acid additionally containing the (n-3) polyunsaturated fatty acid α-linolenic acid [18:3(n-3)], can reduce vulnerability to cardiac arrhythmia in rats. Rats were randomly assigned to one of four experimental diet groups for 12 wk. The fat source in the diets was 12% olive (63% oleic acid), canola (55% oleic, 8% α-linolenic acid), soybean [50% linoleic 18:2(n-6), 7% α-linolenic acid] or sunflower seed oil (64% linoleic acid). Arrhythmias were induced by coronary artery occlusion and reperfusion. Incidence of ventricular fibrillation, mortality and arrhythmia score during reperfusion were significantly lower in rats fed the diet containing canola oil than in those fed the olive oil diet. No difference in the severity of arrhythmias was seen in groups fed diets containing soybean or sunflower seed oils. Analysis of myocardial phospholipid fatty acids showed that consumption of canola oil decreased the ratio of (n-6)/(n-3) polyunsaturated fatty acids relative to the other diets, as does dietary fish oil. These results suggest that regular substitution of canola oil for other dietary lipid sources may assist in reducing the likelihood of a transient ischemic event leading to life-threatening cardiac arrhythmias, but the effectiveness of α-linolenic acid is reduced by high levels of linoleic acid.

Comparison of Single-Dose Cardioplegia in Valvular Heart Surgery: Lactated Ringer's-Based del Nido vs. Histidine-Tryptophan-Ketoglutarate Cardioplegia Solution.

This study evaluated myocardial protection and clinical outcomes when using lactated Ringer's solution as the base solution for del Nido cardioplegia compared with histidine-tryptophan-ketoglutarate (HTK) solution in valvular surgery. From January 2017 to May 2018, 71 adult patients who underwent valvular surgery with del Nido cardioplegia (n=37) or HTK cardioplegia (n=34) were retrospectively analyzed. Patients' characteristics were comparable between groups. Postoperative peak troponin T levels were similar. The del Nido group had a decreased incidence of ventricular fibrillation after aortic cross-clamp removal (13.51 vs. 55.88%; P<0.001), lower total volume of cardioplegia administered (1,000 [1,000, 1,250] vs. 1,800 [1,500, 2,000] mL; P<0.001), shorter hospital stay (6 [5, 8] vs. 7 [6, 10] days; P=0.03), and less postoperative red cell transfusion (34.29 vs. 61.11%; P=0.024). There is no difference in aortic cross-clamping time, postoperative change in left ventricular ejection fraction, intensive care unit stay, duration of inotropic support, new onset of atrial fibrillation, in-hospital mortality, complications, and three-year overall survival rate. Lactated Ringer's-based del Nido cardioplegia can be safely used for valvular surgery with acceptable clinical outcomes compared to HTK cardioplegia.