Incidence Of Ventricular Tachycardia Research Articles

Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR-133a.

Heart failure (HF) is a clinical syndrome caused by impairment of ventricular filling, ejection of blood, or both and is categorized as HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) based on left ventricular function. Cardiac fibrosis contributes to left ventricular dysfunction and leads to the development of HF. Ivabradine, an If current selective specific inhibitor, has been shown to improve the prognosis of patients with HF. However, the effects of ivabradine on cardiac function and fibrosis in HFpEF and HFrEF and the underlying mechanism remain unclear. In the present study, we utilized mouse models to mimic HFpEF and HFrEF and evaluated the therapeutic effects of ivabradine. By treating mice with different doses (10 mg/kg/d and 20 mg/kg/d) of ivabradine for 4 or 8 weeks, we found that a high dose of ivabradine improved cardiac diastolic function in HFpEF mice and ameliorated cardiac diastolic and systolic function and ventricular tachycardia incidence in HFrEF mice. Moreover, ivabradine significantly reduced the activation of cardiac fibroblasts and myocardial fibrosis in mice. Mechanistically, microRNA-133a, which was upregulated by ivabradine, targeted connective tissue growth factor and collagen 1 in cardiac fibroblasts and might contribute to the protective role of ivabradine. Together, our work utilized mouse models to study HFpEF and HFrEF, demonstrated the protective role of ivabradine in HFpEF and HFrEF, and elucidated the potential underlying mechanism, which provides an effective strategy for related diseases.

Atrial fibrillation is associated with increased risk of lethal ventricular arrhythmias

Atrial fibrillation (AF) is associated with various major adverse cardiac events such as ischemic stroke, heart failure, and increased overall mortality. However, its association with lethal ventricular arrhythmias such as ventricular tachycardia (VT), ventricular flutter (VFL), and ventricular fibrillation (VF) is controversial. We conducted this study to determine whether AF can increase the risk of VT, VFL, and VF. We utilized the Korean National Health Insurance Service database for this nationwide population-based study. This study enrolled people who underwent a nationwide health screen in 2009 for whom clinical follow-up data were available until December 2018. Primary outcome endpoint was the occurrence of VT, VFL, or VF in people who were and were not diagnosed with new-onset AF in 2009. We analyzed a total of 9,751,705 people. In 2009, 12,689 people were diagnosed with new-onset AF (AF group). The incidence (events per 1000 person-years of follow-up) of VT, VFL, and VF was 2.472 and 0.282 in the AF and non-AF groups, respectively. After adjustment for covariates, new-onset AF was associated with 4.6-fold increased risk (p < 0.001) of VT, VFL, and VF over 10 years of follow-up. The risk of VT, VFL, and VF was even higher if identification of AF was based on intensified criteria (≥ 2 outpatient records or ≥ 1 inpatient record; hazard ratio = 5.221; p < 0.001). In conclusion, the incidence of VT, VFL, and VF was significantly increased in people with new-onset AF. The potential risk of suffering lethal ventricular arrhythmia in people with AF should be considered in clinical practice.

The oxidation-resistant CaMKII-MM281/282VV mutation does not prevent arrhythmias in CPVT1.

Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited arrhythmogenic disorder caused by missense mutations in the cardiac ryanodine receptors (RyR2), that result in increased β‐adrenoceptor stimulation‐induced diastolic Ca2+ leak. We have previously shown that exercise training prevents arrhythmias in CPVT1, potentially by reducing the oxidation of Ca2+/calmodulin‐dependent protein kinase type II (CaMKII). Therefore, we tested whether an oxidation‐resistant form of CaMKII protects mice carrying the CPVT1‐causative mutation RyR2‐R2474S (RyR2‐RS) against arrhythmias. Antioxidant treatment (N‐acetyl‐L‐cysteine) reduced the frequency of β‐adrenoceptor stimulation‐induced arrhythmogenic Ca2+ waves in isolated cardiomyocytes from RyR2‐RS mice. To test whether the prevention of CaMKII oxidation exerts an antiarrhythmic effect, mice expressing the oxidation‐resistant CaMKII‐MM281/282VV variant (MMVV) were crossed with RyR2‐RS mice to create a double transgenic model (RyR2‐RS/MMVV). Wild‐type mice served as controls. Telemetric ECG surveillance revealed an increased incidence of ventricular tachycardia and an increased arrhythmia score in both RyR2‐RS and RyR2‐RS/MMVV compared to wild‐type mice, both following a β‐adrenoceptor challenge (isoprenaline i.p.), and following treadmill exercise combined with a β‐adrenoceptor challenge. There were no differences in the incidence of arrhythmias between RyR2‐RS and RyR2‐RS/MMVV mice. Furthermore, no differences were observed in β‐adrenoceptor stimulation‐induced Ca2+ waves in RyR2‐RS/MMVV compared to RyR2‐RS. In conclusion, antioxidant treatment reduces β‐adrenoceptor stimulation‐induced Ca2+ waves in RyR2‐RS cardiomyocytes. However, oxidation‐resistant CaMKII‐MM281/282VV does not protect RyR2‐RS mice from β‐adrenoceptor stimulation‐induced Ca2+ waves or arrhythmias. Hence, alternative oxidation‐sensitive targets need to be considered to explain the beneficial effect of antioxidant treatment on Ca2+ waves in cardiomyocytes from RyR2‐RS mice.

Case series on stereotactic body radiation therapy in non-ischemic cardiomyopathy patients with recurrent ventricular tachycardia.

The efficacy of stereotactic body radiation therapy (SBRT) as an alternative treatment for recurrent ventricular tachycardia (VT) is still unclear. This study aimed to report the outcome of SBRT in VT patients with nonischemic cardiomyopathy (NICM). The determination of the target substrate for radiation was based on the combination of CMR results and electroanatomical mapping merged with the real-time CT scan image. Radiation therapy was performed by Flattening-filter-free (Truebeam) system, and afterward, patients were followed up for 13.5 ± 2.8 months. We analyzed the outcome of death, incidence of recurrent VT, ICD shocks, anti-tachycardia pacing (ATP) sequences, and possible irradiation side-effects. A total of three cases of NICM patients with anteroseptal scar detected by CMR. SBRT was successfully performed in all patients. During the follow-up, we found that VT recurrences occurred in all patients. In one patient, it happened during a 6-week blanking period, while the others happened afterward. Re-hospitalization due to VT only appeared in one patient. Through ICD interrogation, we found that all patients have reduced VT burden and ATP therapies. All of the patients died during the follow-up period. Radiotherapy-related adverse events did not occur in all patients. SBRT therapy reduces the number of VT burden and ATP sequence therapy in NICM patients with VT, which had a failed previous catheter ablation. However, the efficacy and safety aspects, especially in NICM cases, remained unclear.

Proarrhythmic potential of metoclopramide in a sensitive whole-heart model.

Metoclopramide (MCP) is a dopamine D2 -receptor antagonist, mainly used to treat post-operative or chemotherapy-induced nausea. While it is very effective in the cure of gastric symptoms, MCP can cause severe neurologic side effects. Furthermore, there is growing evidence for severe arrhythmic side effects resulting from inhibitory effects on cardiac sodium and potassium channels. Thirteen hearts of New Zealand white rabbits were retrogradely perfused, and electrophysiology studies were performed to obtain action potential duration (APD90 ) and effective refractory period (ERP). After generating baseline data, the hearts were perfused with increasing concentrations of metoclopramide (MCP 10µM, MCP 50µM, MCP 100µM) and the standardized protocol was repeated for each concentration. Perfusion with MCP resulted in a significant prolongation of APD90 and QT interval. In parallel, the incidence of ventricular tachycardias was significantly increased by high doses of MCP. This is the first experimental study that investigated the effect of increasing doses of metoclopramide on a sensitive whole-heart model of proarrhythmia. MCP led to a significant increase in action potential duration and QT interval; meanwhile, the number of ventricular tachycardias was significantly increased.

Risk factors of persistent ventricular arrhythmias after mitral valve repair in Barlow disease patients: six-year follow-up

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Improvement in malignant ventricular arrhythmias (VA) has been reported after mitral valve surgery in some mitral valve prolapse patients (MVP) with severe degenerative mitral regurgitation. Mitral annular disjunction, posterior systolic curling, and mitral annular abnormal contractility are associated with arrhythmic MVP and underwent correction during the mitral valve repair. However, mitral valve disease progression and ventricular arrhythmic substrates (left ventricular fibrosis of papillary muscles and basal posterior wall) could be potential substrates for persistent malignant arrhythmias even after surgical correction. Our aim was to evaluate the risk factors of persistent VA after mitral valve repair in Barlow’s disease patients in six-year follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) who underwent mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results All patients survived the operation. There was only one sudden cardiac death on sixth year of follow-up. During 173 person-years of follow-up 3 patients (10%) had developed recurrent moderate to severe (≥2) MR. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT correlated strongly with postoperative end-diastolic LV diameter (EDD rs=.69; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.001). Advanced myxomatous degeneration assessed by pathologists and MV posterior leaflet’s thickness ≥5 mm after repair assessed by echocardiographer associated with postoperative PVCs and VT (rτ=.58; p=.045 and rs=.62; p=.002, respectively). Recurrent MR also strongly associated with postoperative PVCs and VT (rs=.76; p=.0018). In univariate analysis, advanced myxomatous degeneration (p=.008), postoperative end-diastolic LV diameter (p=.001), and low EF (p=.003) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Advanced myxomatous degeneration assessed by pathologists or echocardiographer and postoperative left ventricular remodeling are associated with persistent malignant ventricular arrhythmias. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmias is needed.

Factors associated with recurrent postinfarction ventricular tachycardia following ablation.

INTRODUCTION Ablation of ventricular tachycardia is the main therapy for patients with drug-refractory ventricular tachycardia (VT). Although evidence suggests that VT ablation could lower the incidence of recurrent VT, many cases still develop VT in follow-up. In this study, we performed a systematic review and meta-analysis to examine risk factors for recurrent VT in patients with postinfarction VT who underwent VT ablation. EVIDENCE ACQUISITION We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2020. Included studies were cohort studies, experimental trials, or randomized controlled trials that evaluate the risk of recurrent VT in postinfarction VT patients who underwent VT ablation. Data from each study were combined using random-effects. EVIDENCE SYNTHESIS Thirteen studies involving 1803 postinfarction patients who underwent VT ablation were included. Inducibility after the procedure (pooled HR=1.71, P<0.001), lower baseline left ventricular ejection fraction (LVEF) (pooled HR=0.98, P<0.001) and higher baseline New York Heart Association (NYHA) classification (pooled HR=1.34, P=0.003) were significantly associated with VT recurrence during the follow-up. There was no significant association between age, gender or diabetes mellitus and VT recurrence. CONCLUSIONS Our meta-analysis demonstrated that inducibility after the procedure, lower baseline LVEF and higher baseline NYHA classification were associated with an increased risk of VT recurrence in postinfarction VT patients who underwent VT ablation.

Ventricular tachycardia in patients undergoing 24-h Holter monitoring as preoperative evaluation for noncardiac surgery.

The incidence of ventricular tachycardia (VT) in preoperative evaluation for noncardiac surgery in general hospitals has not been established. The aim of this study was to determine the incidence of VT, characteristics of patients with VT, characteristics of VT, and significance of VT in patients undergoing 24-h Holter monitoring as preoperative evaluation for noncardiac surgery. In 601 patients, VT was detected in 46 patients (7.7%). In patients with VT, left ventricular ejection fraction (LVEF) was lower (62.6 ± 9.3% vs. 66.6 ± 8.9%, p = 0.003), and B-type natriuretic peptide (BNP) was higher compared with patients without VT (median, 52.5pg/mL vs. 32.8pg/mL, p = 0.02). The maximum number of consecutive beats of VT was more frequent in the patients with LVEF < 50% than in the patients with LVEF ≥ 50% (median, 11.5 beats vs. 3.0 beats, p = 0.01). Forty patients (87%) underwent scheduled surgery without major complications.

The Effect of Magnesium on Reperfusion Arrhythmias in STEMI Patients, Treated With PPCI. A Systematic Review With a Meta-Analysis and Trial Sequential Analysis

Aims: The restoration of coronary circulation plays a crucial role in treating ST-segment elevation myocardial infarction (STEMI), however successful reperfusion with primary percutaneous coronary intervention (PPCI) may induce life-threatening arrhythmias. The relation between myocardial electrical instability, as a background factor in reperfusion arrhythmia, and magnesium administered periprocedurally is still questionable. Several randomized clinical trials have been conducted predominantly in the thrombolysis era. Due to the contradictory results of these studies, there is little evidence of the potential preventive effect of magnesium on reperfusion arrhythmias. The aim of our study is to review and meta-analytically analyze data from all studies published so far in the PPCI era, comparing STEMI patients who have undergone primary PCI and received either magnesium or a placebo before the reperfusion procedure.Methods and Results: Our meta-analysis follows the points in the PRISMA protocol and, meets all of their criteria. We conducted a search in five scientific databases using the following keyword combination: (myocardial infarction OR myocardial injury OR acute coronary syndrome OR acs OR stemi) AND magnesium. The 7,295 collected publications were filtered with the Endnote program by title, abstract and full-text based on predefined criteria. A statistical analysis was performed on three randomized-controlled trials using three common parameters, involving 336 patients Trial sequential analysis (TSA) was applied to assess the risk of random error associated with sparse data and multiple testing which can affect cumulative meta-analysis. The incidence of ventricular tachycardias (VTs) was not significantly increased in the non-magnesium control group. (OR: 1.36; CI: 0.619; −2.986, P = 0.263). For the ejection fraction (EF), a non-significant decrease was observed in the magnesium group by weighted mean difference calculation. (WMD: 7.262, 95% CI: −0.238; 0.053; P = 0.057). There was significant decrease in the infarct zone wall motion index (IZWMSI) in the magnesium treatment group. (WMD: 0.384, 95% CI: −0.042; 0.811, P = 0.015). Based on the TSA assessments, the results of all parameters are not significant, objectively demonstrating the lack of reasonable data pertaining to our question.Conclusions: The preventive effect of magnesium on reperfusion arrhythmia associated with primary PCI can still be considered contradictory based on previous studies. In our study, we found, that magnesium is ineffective with a very weak evidence, due to the small number of patients and the biases of the included studies, and a well-designed clinical trial is needed in this area, based on the TSA.

Abstract 16495: Activation of Notch Signaling in the Heart Promotes Electrical Disturbances

Notch1 receptor signaling is active in the heart during embryonic development, is progressively silenced after birth, and it is partly restored in the adult myocardium following ischemic damage, a condition characterized by occurrence of arrhythmias. We previously reported that inducible overexpression of Notch1 intracellular domain (gain-of-function, NGoF) in adult mouse cardiomyocytes alters ionic currents and action potential profile. But the consequences of Notch1 signaling activation on electrical properties and arrhythmogenicity of the entire heart remain to be defined. For this purpose, electrocardiograms were obtained in NGoF (n=25) and corresponding control (Ctrl, n=13) mice in the conscious state, over a 10 min period. Electrical signals were obtained at baseline and following administration of an arrhythmogenic cocktail (120 mg/kg BW caffeine and 2 mg/kg BW epinephrine) to test the propensity of these animals to develop electrical disturbances. Moreover, information was also obtained in mice with inducible Notch1 gene deletion for complete silencing of Notch1 signaling (Notch1 loss-of-function, NLoF, n=5). At baseline, heart rate and QT interval duration were comparable in NGoF (689±30 bpm; 49±2 ms), Ctrl (703±29 bpm; 48±1 ms), and NLoF (697±50 bpm; 48±1 ms) animals. Only a small fraction (~8%) of NGoF mice presented isolated premature ventricular complexes (PVCs) or junctional rhythm, but these events were not observed in Ctrl and NLoF mice. Administration of the arrhythmogenic cocktail induced PVCs in the majority of Ctrl (~56%) and NLoF (~60%) mice and in almost all NGoF animals (~92%). Also recurrent PVCs (≥10/10 min) were 1.7-2.1-fold higher in NGoF mice, with respect to NLoF and Ctrl. Importantly, 77% of NGoF mice developed ventricular tachycardia (VT), whereas VT occurrence was attenuated in Ctrl (56%) and NLoF (~40%) animals. Incidence of sustained VT was 1.7-fold higher in NGoF mice, with respect to Ctrl. Similarly, bidirectional VT was higher in NGoF (~62%), with respect to Ctrl (~52%) and NLoF (~40%). Thus, Notch signaling activation in the heart of experimental animals tends to enhance the occurrence of electrical disturbances, a factor that may be involved in the arrhythmogenic behavior of the post-infarcted myocardium.

Long-term outcomes amongst adults with anatomic repair for transposition of the great arteries: not as perfect as we would have hoped?

Abstract Background The arterial switch operation (ASO) has replaced atrial switch procedures for D-transposition of the great arteries (D-TGA), with 90% of patients now reaching adulthood. However, patients may have residual lesions and/or sequelae, some of which may remain unrecognized, necessitating lifelong specialist surveillance. We examined the cardiac outcomes of a large number of contemporary ASO patients under tertiary adult congenital heart disease (ACHD) care. Methods We examined late major adverse cardiovascular events (MACE) in adult TGA patients (&amp;gt;16 years) who underwent an ASO between 1981 and 2003 and continued their follow-up in 2 tertiary ACHD centers. MACE were defined as death, re-intervention, myocardial ischemia, arrhythmia, stroke/TIA, infective endocarditis and heart failure. Results Overall, 199 patients (66% male, mean age 27±5 years) were followed in adult life for a median of 10 years [IQR 7–15] and were included in this study. Overall survival during this period was 99.5% (95% confidence interval [CI]: 94.4%-99.8%). Sixty-two (31.2%) patients experience MACE, including 52 reinterventions. MACE and reintervention-free survival at 20, 30 and 35 years were 87.6%, 58.6%, 50.6% and 89.5%, 69.1, 61%, respectively. Atrial arrhythmia was the most frequent cardiac event with an incidence of 5.5 cases per 1000 patient-years, whereas incidence of ventricular tachycardia and sudden cardiac death was 1.8‰ and 0.9‰ patient-years, respectively. Coronary artery disease was diagnosed in 6 (3%) patients, of whom 4 had symptoms, 1 had ST depression on ECG at rest and 3 had abnormal wall motion on echocardiography. The most frequent indication for reoperation was right ventricular outflow tract obstruction (n=35/52, 63.7%), whereas left ventricular outflow tract (LVOT) re-interventions rate increased significantly during adulthood compared to childhood from 1% to 5%, p=0.03 (Figure 1). On multivariate analysis, history of cardiac complications during infancy (HR 2.3, 95% CI:1.3–4.0, p&amp;lt;0.01) and uncommon coronary patterns (HR for type A versus B/C/D/E 0.47, 95% CI:0.26–0.83, p&amp;lt;0.01) were independent predictors of MACE in adulthood. At the latest follow-up, 90.9% of patients were functional class I, left ventricular ejection fraction was 59.6±6.5% and peak oxygen uptake 71.1±24.9% predicted. At least moderate neoaortic regurgitation and aortic dilatation (≥40mm) were present in 8.0% and 35.2%, respectively, with more than mild pulmonary stenosis in 19.6%. Conclusion Adult patients with ASO for TGA have a low late mortality. However, MACE are common requiring reintervention, particularly for RVOT obstruction and neo-aortic valve dysfunction, the latter with rising rates during adulthood. Patients with cardiovascular complications during childhood are at the highest risk for MACE. All patients merit life-long tertiary care. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Assistance Publique des Hôpitaux de Paris

Idiopathic HFrEF. Is there room left for defibrillators?

Abstract Background and aim Prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is class 1 recommendation for heart failure (HF) patients with reduced ejection fraction (HFrEF) even though its proven advantage is weaker among nonischemic aetiology. In fact, in an era where both optimal medical therapy (OMT) and cardiac resynchronization therapy (CRT) significantly reduce sudden cardiac death (SCD), it is questionable whether ICD still have additional value. The aim of this study was to assess the current benefit of ICDs in preventing sudden cardiac death through resuscitated cardiac arrest (RCA), appropriate therapy for sustained ventricular tachycardia (VT) or fibrillation (VF) in a contemporary population of idiopathic HFrEF patients. Methods Single-centre retrospective study of consecutive symptomatic (NYHA class II to IV) idiopathic HFrEF patients with an ICD (either alone or in association with CRT), and remote monitoring with the corresponding software (MerlinTM, LatitudeTM, CarelinkTM, MicroPortTM or BiotronikTM) to assure appropriate event supervising. Idiopathic aetiology was assumed after excluding other probable causes. Coronary angiogram was required to exclude ischemic aetiology. Only those with prophylactic ICD implantation were included. RCA was defined as collapse with clinical signs of cardiac arrest and VF or VT appropriately terminated by ICD. In order to be sustained, VT episode had to have last at least 30 seconds. Results From 781 remote monitoring controlled patients, a total of 187 consecutive symptomatic idiopathic HFrEF patients with an ICD (125 men, mean age 64±18 years) were enrolled. Patients were on optimal medical therapy (ACEi/ARB: n=168, 90%; BB: n=154, 82%; mineralocorticoid antagonists: n=91, 49%; CRT: n=130, 70%; see Table). After a median follow-up of 99 months (IQR 62.2), RCA occurred in 10.7% (n=20) and 36.9% (n=69) had appropriately terminated VT. Both left ventricular ejection fraction (LVEF) improvement and CRT implantation did not independently reduce the incidence of RCA and VT requiring ICD therapy (OR, 1.02; 95% CI, 0.99–1.05; P=0.146 and OR, 0.85; 95% CI, 0.34–2.13; P=0.728; respectively). All cause mortality was 20 (10.7%). Inappropriate therapy was given as shocks to 41 patients (21.9%) and as antitachycardia pacing (ATP) to 30 (16%), opposing with appropriately given therapy to 43 (23%) and 63 (33.7%) patients, respectively (see Figure), contributing to a net clinical benefit (NCB) of 18.8%, favouring ICD implantation. Conclusion In this contemporaneous real-world population of symptomatic idiopathic HFrEF patients, episodes of impending cardiac death were frequent. Prophylactic ICD implantation seems to have added further benefit reducing SCD on top of optimal medical therapy, LVEF improvement and coexisting CRT. Funding Acknowledgement Type of funding source: None

Modulating the Infarcted Ventricle’s Refractoriness with an Epicardial Biomaterial

Patients diagnosed with heart failure with reduced ejection fraction (HFrEF) are at increased risk of monomorphic ventricular tachycardia (VT) and ventricular fibrillation. The presence of myocardial fibrosis provides both anatomical...

SOD2 deficiency in cardiomyocytes defines defective mitochondrial bioenergetics as a cause of lethal dilated cardiomyopathy

Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O2•-) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 (SOD2Δ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the cristae and vacuole formation. Noninvasive echocardiographic measurements in SOD2Δ mice showed dilated cardiomyopathic features such as decreased ejection fraction and fractional shortening along with increased left ventricular internal diameter. An increased incidence of ventricular tachycardia was observed during electrophysiological studies of the heart in SOD2Δ mice. Oxidative phosphorylation (OXPHOS) measurement using a Seahorse XF analyzer in SOD2Δ neonatal cardiomyocytes and adult cardiac mitochondria displayed reduced O2 consumption, particularly during basal conditions and after the addition of FCCP (H+ ionophore/uncoupler), compared to that in SOD2fl hearts. Measurement of extracellular acidification (ECAR) to examine glycolysis in these cells showed a pattern precisely opposite that of the oxygen consumption rate (OCR) among SOD2Δ mice compared to their SOD2fl littermates. Analysis of the activity of the electron transport chain complex identified a reduction in Complex I and Complex V activity in SOD2Δ compared to SOD2fl mice. We demonstrated that a deficiency of SOD2 increases reactive oxygen species (ROS), leading to subsequent overproduction of 4-HNE inside mitochondria. Mechanistically, proteins in the mitochondrial respiratory chain complex and TCA cycle (NDUFS2, SDHA, ATP5B, and DLD) were the target of 4-HNE adduction in SOD2Δ hearts. Our findings suggest that the SOD2 mediated 4-HNE signaling nexus may play an important role in cardiomyopathy.

Factors associated with recurrent postinfarction ventricular tachycardia following ablation.

Ablation of ventricular tachycardia is the main therapy for patients with drug-refractory ventricular tachycardia (VT). Although evidence suggests that VT ablation could lower the incidence of recurrent VT, many cases still develop VT in follow-up. In this study, we performed a systematic review and meta-analysis to examine risk factors for recurrent VT in patients with postinfarction VT who underwent VT ablation. We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2020. Included studies were cohort studies, experimental trials, or randomized controlled trials that evaluate the risk of recurrent VT in postinfarction VT patients who underwent VT ablation. Data from each study were combined using random-effects. Thirteen studies involving 1803 postinfarction patients who underwent VT ablation were included. Inducibility after the procedure (pooled HR=1.71, P<0.001), lower baseline left ventricular ejection fraction (LVEF) (pooled HR=0.98, P<0.001) and higher baseline New York Heart Association (NYHA) classification (pooled HR=1.34, P=0.003) were significantly associated with VT recurrence during the follow-up. There was no significant association between age, gender or diabetes mellitus and VT recurrence. Our meta-analysis demonstrated that inducibility after the procedure, lower baseline LVEF and higher baseline NYHA classification were associated with an increased risk of VT recurrence in postinfarction VT patients who underwent VT ablation.

Angiotensin receptor-neprilysin inhibitior (thiorphan/irbesartan) decreased ischemia-reperfusion induced ventricular arrhythmias in rat; in vivo study

Ventricular arrhythmias are considered as a major risk of sudden cardiac death. This study was designed to investigate the potential effects of angiotensin receptor neprilysin inhibitor; thiorphan/irbesartan (TH/IRB) combination therapy on myocardial ischemic-reperfusion (I/R)-induced arrhythmia. Fifty male Wistar rats were divided into 5 groups; (I, II): Sham, I/R both received DMSO intraperitoneally before the procedure. (III, IV, V): TH/IRB + IR (0.1/5 mg/kg, 0.1/10 mg/kg and 0.1/15 mg/kg). The drugs were injected intraperitoneally 15 min before I/R induction. Electrocardiograms changes, mean arterial blood pressure, incidence of ventricular tachycardia (VT), incidence of ventricular fibrillation (VF) and arrhythmia score were assessed. Cardiac levels of creatinine kinase–MB (CK-MB), Malondialdehyde (MDA), superoxide dismutase (SOD), endothelin-1 (ET-1), ATP content, and Na+/K+-ATPase pump activity were measured. TH (0.1 mg/kg) in combination with IRB (5, 10 and 15 mg/kg) produced significant decrease in QTc interval duration, ST height, incidence of VT and VF, duration of VT + VF, and arrhythmia score compared to I/R group. All treated groups showed significant decrease in the cardiac levels of: CK-MB, MDA and ET-1 and significant increase in SOD, ATP content, and Na+/K+-ATPase pump activity compared to I/R. TH/IRB + IR (0.1/10 mg/kg) group produced significant decrease in CK-MB, MDA and ET-1 and a significant increase in SOD, ATP content, and Na+/K+-ATPase pump activity compared to other treated groups. In conclusion, angiotensin receptor neprilysin inhibitor (thiorphan/irbesartan) decreased arrhythmia score and decreased cardiac damage. These could be explained in part by its ability to decrease oxidative stress and ET-1, increase ATP, and Na+/K+-ATPase pump activity in this rat model of I/R-induced arrhythmia.

Islets of heterogeneous myocardium within the scar in cardiac magnetic resonance predict ventricular tachycardia after myocardial infarction

We assessed findings in cardiac magnetic resonance (CMR) as predictors of ventricular tachycardia (VT) after myocardial infarction (MI), which could allow for more precise identification of patients at risk of sudden cardiac death. Forty-eight patients after prior MI were enrolled and divided into twogroups: with (n = 24) and without (n = 24) VT. VT was confirmed by electrophysiological study and exit site was estimated based on 12-lead electrocardiogram. All patients underwent CMR with late gadolinium enhancement. The examined groups did not differ significantly in clinical and demographical parameters (including LV ejection fraction). There was a significant difference in the infarct age between the VT and non-VT group (15.8 ± 8.4 vs7.1 ± 6.7 years, respectively; P = .002), with the cut-off point at the level of 12 years. In the scar core, islets of heterogeneous myocardium were revealed. They were defined as areas of potentially viable myocardium within or adjacent to the core scar. The number of islets was the strongest independent predictor of VT (odds ratio [OR], 1.42; confidence interval [CI], 1.17-1.73), but total islet size and the largest islet area were also significantly higher in the VT group (OR, 1.04; CI, 1.02-1.07 and OR, 1.16; CI, 1.01-1.27, respectively). Myocardial segments with fibrosis forming 25%-75% of the ventricular wall were associated with a higher incidence of VT (7.5 ± 2.1 vs5.7 ± 2.6; P = .014). Three-dimension CMR reconstruction confirmed good correlation of the location of the islets/channels with VT exit site during electroanatomical mapping in five cases. The identification and quantification of islets of heterogeneous myocardium within the scar might be useful for predicting VT in patients after MI.

Abstract P116: Chronic Kidney Disease And Cardiac Arrhythmias: A Systematic Review and Meta-analysis

Background: Chronic kidney disease (CKD) strongly predicts sudden cardiac death and may elevate the risk of certain cardiac arrhythmias like atrial fibrillation; however, the relationships between CKD and various types of arrhythmia are not well-characterized. Methods: We performed a systematic review and meta-analysis by searching Embase and PubMed for prospective, cross-sectional, and case-control studies examining the associations of two key CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with arrhythmias in adults that were published until July 2018. We performed qualitative assessment of studies using the Newcastle Ottawa Quality Assessment Scale. We pooled the results using random-effects models. Results: Among 16,245 articles, we identified 34 prospective (n=24,213,233), 21 cross-sectional (n=253,328), and 4 case-control (n=1,694) studies that included diverse study populations from 19 countries and were mostly high quality. Most prospective studies examined the relationship between eGFR and atrial fibrillation (AF), and demonstrated that lower eGFR was associated with a higher risk of AF (pooled hazard ratio [HR] 1.72 [95% CI: 1.30, 2.27] comparing reduced vs. referent eGFR groups)[ Figure ]. A few studies examined albuminuria and demonstrated its associations with AF (pooled HR 2.16 [95% CI: 1.74, 2.67] comparing high vs. low albuminuria). Results were similar for cross-sectional studies. Four prospective studies reported a higher incidence of ventricular tachycardia resulting in ICD shock according to reduced eGFR (pooled HR 2.32 [95% CI: 1.74, 3.09] comparing reduced vs. referent eGFR groups). Limited number of studies examined other types of arrhythmia. Conclusion: We identified robust data on the relationship between CKD (eGFR and albuminuria) and AF. Reduced eGFR was associated with life-threatening ventricular arrhythmias. Our review highlights the need of future studies for non-AF arrhythmias, especially in the context of albuminuria.

Urolithin B improves cardiac function and reduces susceptibility to ventricular arrhythmias in rats after myocardial infarction

Cardiac fibrosis and inflammation play critical roles in ventricular remodelling after myocardial infarction (MI). Urolithin B (UB), a metabolite of ellagitannin-rich foods, has various biological activities, but its effect on ventricular remodelling after MI has not been determined. The present study evaluated whether UB inhibited ventricular structural remodelling and decreased the occurrence of ventricular arrhythmias after MI. Sprague-Dawley (SD) rats underwent ligation of the left anterior descending coronary artery before randomization to receive phosphate-buffered saline (PBS) or UB at doses of 2.5 mg/kg/day and 5 mg/kg/day via intraperitoneal administration or sham ligation. Cardiac function was assessed using echocardiography, haemodynamic detection and brain natriuretic peptide (BNP) levels 2 weeks post-MI. Hearts were used for electrophysiological testing and molecular and histological analyses. UB (5 mg/kg/day) significantly protected against post-MI cardiac dysfunction. UB markedly reduced infarct areas and myocyte size and attenuated cardiac fibrosis and inflammation post-MI. UB decreased the incidence of ventricular tachycardia and ventricular fibrillation compared to the MI group. We determined that UB inhibited the phosphorylation of JAK2/STAT3 and Smad2/3 signalling molecules. Our data suggest that UB reduces the occurrence of malignant ventricular arrhythmias after MI, which is likely associated with attenuation of ventricular structural remodelling via inactivation of the JAK2/STAT3 and Smad2/3 signalling pathway.

423 Effects of mitral valve repair on left ventricular remodeling and ventricular arrhythmia in mitral valve prolapse patients: five-year follow-up

Abstract Introduction There is limited data on the efficacy of surgical repair in reducing ventricular arrhythmia (VA) in mitral valve prolapse (MVP) patients. Improvement in malignant ventricular arrhythmias has been reported only in isolated cases after mitral valve surgery. Our aim was to evaluate the possible effects of mitral valve repair on left ventricular (LV) reverse remodeling and incidence of VA in MVP patients in mid-term follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) undergoing mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography extended with speckle-tracking echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. Atrial fibrillation, PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results During 144 person-years of follow-up no deaths, and 3 cases (10%) of recurrent moderate or severe (≥2) MR occurred. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVC and VT correlates strongly with postoperative end-diastolic LV diameter (EDD rs=.70; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.01), but not postoperative MR (p&amp;gt;.05). EDD (58.8 ± 7.6 mm vs. 49.9 ± 5.6 mm; p=.00001) and EDV (156.6 ± 32.1 ml vs. 104.1 ± 22.8 ml; p=.00001) decreased in 1st year after repair with non-significant changes in EF (63.8 ± 12.8% vs. 59.6 ± 14.5%; p=.20), global systolic longitudinal strain –13.8 ± 2.5% vs. –14.6 ± 2.7%; p=.20) and SR (–0.93 ± 0.12 s-1 vs. –0.98 ± 0.13 s-1; p=.09) values. In univariate analysis, postoperative end-diastolic LV diameter (p=.001), low EF (p=.003), myxomatous degeneration (p=.008) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Mitral valve repair in MVP with severe mitral regurgitation is associated with reduction in ventricular arrhythmia, which strongly correlates with postoperative LV dimensions and function. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmia is needed.