Risk Factor For Ventricular Arrhythmias Research Articles

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

Risk factors for ventricular arrhythmias after emergency percutaneous coronary intervention in elderly patients with acute myocardial infarction

Risk factors for ventricular arrhythmias after emergency percutaneous coronary intervention in elderly patients with acute myocardial infarction

Left ventricular hypertrophy and ventricular ectopy in mitral valve prolapse

Abstract Background Mitral valve prolapse (MVP) is associated with left ventricular hypertrophy (LVH). Individuals with sudden death ascribed to MVP have increased ventricular mass on autopsy. Whether LVH is a risk factor for ventricular arrhythmia in MVP is unknown. Purpose We aimed to describe factors associated with LVH in MVP and the association of LVH with ventricular ectopy in MVP. Methods We studied all 637 patients aged 18 - 90 years with MVP on echocardiography between 2016-19 at our institution (median age [interquartile range] 64.3 [52.3-73.6] years; 52.6% female; 16.2% African American). Echocardiograms were reviewed for LVH, ventricular size and function, and valvular pathology. Complex or frequent ventricular ectopy (cfVE) was defined as >1% burden of premature ventricular complexes or non-sustained ventricular tachycardia on ambulatory electrocardiogram or ≥2 premature ventricular complexes on a 10-second electrocardiogram. Multivariate logistic regression was used to assess relationships between MVP, LVH, and known associations of cfVE in MVP. Resul­ts: LVH was present in 144 (22.6%) patients. A history of hypertension (HTN) was present in 78/144 (54.2%) with LVH vs. 204/493 (41.5%) of those without LVH (p=0.008). On multivariate analysis, LVH was independently associated with moderate to severe mitral regurgitation (odds ratio [95% confidence interval] 3.6 [2.4-5.6]) and heart failure (3.2 [2.0-5.1]), but not HTN (1.3 [0.9-2.0], p=0.205). cfVE was present in 55/144 (38.2%) with LVH vs. 127/493 (25.8%) without LVH (p=0.005). Among those without HTN, cfVE was present in 26/66 (39.4%) of those with LVH vs. 68/288 (23.6%) without LVH (p=0.013). On multivariate analysis, independent predictors of cfVE were age (odds ratio [95% confidence interval] 2.9 [1.1-8.1], p=0.035), mitral annular disjunction (3.2 [1.9-5.3], p<0.0001), heart failure (2.4 [1.4-4.0], p=0.001), bileaflet MVP (2.2 [1.4-3.3], p<0.001), and electrocardiogram inferior lead T-wave inversion (2.2 [1.4-3.4], p<0.001), but not LVH (1.2 [0.7-1.9], p=0.486) whether in presence of HTN (1.0 [0.5-1.9], p=0.959) or absence of HTN (1.4 [0.7-2.8], p=0.344). Conclusion LVH is a common finding in MVP and is associated with mitral regurgitation and heart failure. LVH in MVP is not associated with increased ventricular ectopy. Ventricular ectopy in MVP is related to mitral morphological factors and heart failure.Multivariate predictors of cfVECharacteristics with and without LVH

Ceftriaxone and the Risk of Ventricular Arrhythmia, Cardiac Arrest, and Death Among Patients Receiving Lansoprazole

The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes. To compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality. A retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021. Lansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment. The primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications. Of the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality. The findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.

The Impact of Chronic Disease on the Corrected QT (QTc) Value in Women in a British Columbia First Nations Population

BackgroundIndigenous women have higher rates of chronic disease than Indigenous men and non-Indigenous women. Long QT syndrome (LQTS) can be inherited or acquired; the latter may occur with chronic disease. A prolonged corrected QT value (QTc) is an independent risk factor for ventricular arrhythmias and sudden death, but few studies have quantified the impact of chronic disease on the QTc. We assessed the association between chronic disease and QTc prolongation in a population of First Nations women previously ascertained to study a high rate of inherited LQTS due to a unique genetic (founder) variant in their community. MethodsThis substudy focusing on women expands on the original research where patients with clinical features of LQTS and their relatives were assessed for genetic variants discovered to affect the QTc. Medical records were retrospectively reviewed and chronic diseases documented. Using multivariate linear regression, adjusting for the effect of genetic variants, age, and QTc-prolonging medications, we evaluated the association between chronic disease and the QTc. ResultsIn total, 275 women were included. After adjustments, a prolonged QTc was associated with coronary artery disease (26.5 ms, 95% confidence interval [CI] 9.0-44.1 ms; P = 0.003), conduction system disease (26.8 ms, 95% CI 2.2-51.4 ms; P = 0.033), rheumatoid arthritis (28.9 ms, 95% CI 12.7-45.1 ms; P = 0.001), and type 2 diabetes mellitus (17.9 ms, 95% CI 3.6-32.3 ms; P = 0.015). ConclusionsThis quantification of the association between chronic disease and QTc prolongation in an Indigenous cohort provides insight into the nongenetic determinants of QTc prolongation. Corroboration in other populations will provide evidence for generalisability of these results.

Correlations between Cardiovascular Risk Factors and Ventricular Arrhythmias Following Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction.

Ventricular arrhythmias (VAs), which result from acute myocardial infarction and revascularization, are preventable causes of sudden cardiac death. This study aimed to determine the incidence, types, and risk factors of VAs in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). This cross-sectional study was conducted at the cardiology department of a tertiary care cardiac center in Zanjan, Iran. All the patients were monitored during hospitalization, and the incidence of cardiac arrhythmias and the outcomes were recorded. Among 315 patients, the mean age was 62.14±10.11 years, and 76.2% were male. Male gender was significantly associated with VA occurrence (P=0.038). Among the patients, 50.5% had VAs, of which 26.4% were sustained ventricular tachycardia (sustained VT) and ventricular fibrillation (VF). Sustained VT and VF, but not total arrhythmias, were more common in anterior infarctions. Most arrhythmias occurred during the first 12 hours, and frequent premature ventricular contractions (43.3%) and idioventricular rhythm (20.1%) were the most common. A history of PCI and coronary artery bypass grafting (CABG) was associated with substantially reduced arrhythmias (P=0.017 and P=0.013, respectively). However, cardiovascular risk factors exerted no statistically significant effects on the VA type. Approximately half of our patients experienced reperfusion-induced VAs. Overall, gender and a history of PCI and CABG were significantly associated with VA occurrence. Therefore, males and patients without a positive history of PCI and CABG should receive antiarrhythmic drugs as a precaution.

Increased Risk of Arrhythmias in Active Acromegaly with Complications and Persistent Uncontrolled Active Acromegaly

Objective: Previous studies showed acromegaly have significant higher prevalence of ventricular arrhythmias and often complicated by diabetes mellitus (DM) and hypertension (HT). Both HT and DM are notoriously associated with the development of arrhythmias. However, the effect of complication (DM and/or HT) in acromegaly on ventricular arrhythmias and the risk of ventricular arrhythmias in acromegaly accept therapy but no control is largely unknown. Methods: A cross-sectional study with 307 acromegaly and 303 patients with non-functional pituitary adenoma as control group. All subjects divided into acromegaly with/without complication and controls with/without complication. In the longitudinal study, 30 persistent uncontrolled active acromegaly with at least three months follow-up. Electrocardiographic Measurements, laboratory examination, and clinical data collection performed in all subjects. QT interval corrected for heart rate (QTc) analysed among groups. Results: QTc in acromegaly population significantly increased compared to controls (p<0.001). Factorial design twoway ANOVA correcting age revealed significant main effects of complication (p=0.016) and acromegaly (p<0.0001), as well as positive interactions between complication and acromegaly (P<0.038) on QTc. Persistent uncontrolled active acromegalic patients after therapy showed QTc significantly increase in follow-up relative to pre-treatment (p<0.0001). The normalized GH level (r=0.11, p<0.05) and complication (r=0.25, p<0.0001) have a significant positive correlation with QTc in acromegaly. Conclusions: Acromegaly is an independent risk factor for ventricular arrhythmias and acromegaly with complication have an elevated risk for ventricular arrhythmia. Persistent uncontrolled acromegaly, who have significantly decreased in serum GH/IGF-1 levels relative to pre-treatment, also enhance the risk of ventricular arrhythmia.

Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators.

Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far. The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs). Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee. A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95%CI: 0.8%-1.5%) vs 2.2% (95%CI: 1.8%-2.6%) in men (P< 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95%CI: 0.76-1.97; P=0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95%CI: 0.81-2.19; P=0.30), with 24 women (49.0%) experiencing at least 1complication. Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

CE-522-03 LONGITUDINAL PREDICTION OF VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator (https://www.arvcrisk.com) stratifies risk for ventricular arrhythmia (VA) at the time of ARVC diagnosis. However, the risk factors included in the ARVC calculator change with time, and how well it performs at follow up evaluations is unknown. To identify the temporal trends of VA risk factors and test the longitudinal performance of the ARVC calculator. This was a retrospective analysis of ARVC patients without prior VA (sustained ventricular tachycardia (VT), appropriate ICD therapy, sudden cardiac death/arrest) enrolled in the Johns Hopkins Hospital ARVC registry and Netherlands ACM registry. Risk factors for VA (age, sex, history of cardiac syncope, burden of PVC on 24-hour heart monitor, history of non-sustained VT, number of T-wave inversions on ECG, and right ventricular ejection fraction) were assessed at the time of ARVC diagnosis and upon repeat evaluations. The 5-year risk of VA was predicted longitudinally using 1) the ARVC calculator (baseline risk factors), 2) the ARVC calculator (updated risk factors), 3) time varying Cox regression. 408 patients (37±15 years old, 40% male) were followed for a median of 5.2 [2.8, 9.6] years, during which time 132 experienced a first VA (4.0% events/year). Comparison of risk factors at baseline versus at >5 years of follow up revealed decreases in 24-hour PVC Burden (3,560 vs 2,510) and prevalence of non-sustained VT on the most recent Holter (53% vs 27%), and an increase in number of T-wave inversions (3.4 vs 3.9 leads). Prevalence of right ventricular dysfunction was unchanged. When calculated using baseline risk factors, the ARVC calculator’s ability to predict 5-year VA risk worsened after 3 years of follow up (from ROC-AUC 0.82 at baseline to 0.69 by 5 years). When calculated using updated risk factors, the ARVC calculator (ROC-AUC 0.77) performed as well as time varying Cox regression (ROC-AUC 0.77) after 5 years of follow up (Figure). Risk factors for VA in ARVC change over time. Up-to-date assessment of these risk factors is warranted for VA risk stratification at evaluations beyond 3 years from the time of initial ARVC diagnosis.

The Relationship between T-Wave Alternans and Adverse Cardiac Events in Patients with Congenital Long QT Syndrome: A Systematic Review and Meta-Analysis

Background: T-wave alternans (TWA) is a risk factor of ventricular arrhythmias or sudden cardiac death (SCD) in patients with ischemic cardiomyopathy. Nevertheless, the relationship between TWA and adverse cardiac events (ACE) in patients with congenital long QT syndrome (LQT) remains controversial. Methods: A systematic electronic search of PubMed, Embase and the Cochrane Library was conducted from database inception dates to 28 April 2021 and assessed the relationship between TWA and ACE in patients with LQTS. Sub-group analysis evaluated the association between microvolt TWA (MTWA) and ACE in different monitoring models and ECGlead numbers. Results: A pooled analysis of seven studies of 625 patients with LQTS showed that TWA was significantly associated with ACE (OR 3.16, 95%CI 1.86–5.37, P < 0.001). Advanced analysis showed that macroscopic TWA was significantly related to ACE (OR 6.01, 95%CI 2.96–12.21, P < 0.001), while MTWA did not (OR 0.92, 95%CI 0.37–2.30, P = 0.85). Sub-group analysis showed that MTWA recorded in 24 h continuous ECG (OR 6.79, 95%CI 0.80–57.75, P = 0.08) might have a stronger association with ACE than recorded in stress ECG (OR 0.28, 95%CI 0.07–1.10, P = 0.07). No difference was observed between MTWA measured in multi-lead ECG and limited ECG leads (P = 0.15). Conclusions: Macroscopic TWA was significantly related to ACE in patients with LQTS. In terms of MTWA, MTWA recorded in 24 h continuous ECG might have a stronger association with ACE than stress ECG, but still deserves further evaluation.

Illusion of coronary artery chronic total occlusion-associated ventricular arrhythmia: results from a multi-centre study

Abstract Background/Introduction Coronary artery chronic total occlusion (CTO) is frequently encountered in patients with established coronary artery disease (CAD) with a reported incidence of more than thirty percent in this population (1). A previous large single-centre study established CTO as an independent risk factor for occurrence of ventricular arrhythmia in patients with ICD and ischemic heart disease (2). The significance of CTO in all-comers has not been investigated. In this large retrospective data, it was analysed that there is no significant difference in ventricular arrhythmia occurrence in patients with CTO versus those with CAD and no CTO. Purpose The purpose of this study is to examine the association between CTO and ventricular arrhythmia in patients with CAD using a pooled de-identified database. Methods This retrospective observational study used IBM Explorys, which is a pooled de-identified multi-institutional database of more than 60 million unique patients in the United States. A search was done to identify patients with CTO and those with CAD with the exclusion of CTO diagnosis. The data were analysed for ventricular tachycardia (VT) and/or ventricular fibrillation (VF) occurrence. The data were stratified by presence of systolic HF to identify possible effect modification. Statistical analysis was performed by calculating odds ratios (OR) with associated confidence intervals. Results Among the 190 patients with the diagnosis of CTO, 11.8% had VT/VF. Of the 2,796,600 patients with CAD and no CTO, 6.9% had VT/VF. The diagnosis of CTO was associated with an increased risk for VT/VF with OR 1.7143 (1.0786, 2.7247), p&amp;lt;0.05. Upon stratification by presence or absence of systolic HF, there was no statistically significant difference in occurrence of VT/VF in the two strata. In the systolic HF group, the OR was 1.4331 (0.6708, 3.0619), p=0.47; the no systolic HF group had OR 0.9717 (0.5123, 1.843), p=0.92. In patients with CAD, the diagnosis of systolic HF was associated with an increased risk of CTO with OR 2.5616 (1.7268, 3.7999), p&amp;lt;0.05. Conclusion Stratification by presence or absence of systolic HF yielded inconsistent and statistically insignificant odds ratios compared to the all-comers group, suggesting effect modification by HF with no statistically significant association between CTO and VT/VF. These findings from this large multicentre retrospective data suggest that CTO itself is not an independent risk factor for ventricular arrhythmia in patients with CAD. Limitations of this study include that it is a retrospective pooled analysis without individualised data on ejection fraction and the inability to distinguish if the CTO was infarct-related. Further prospective studies are needed to evaluate the significance of CTO in patients with CAD as it pertains to ventricular arrhythmia. Funding Acknowledgement Type of funding sources: None.

Infarct-related chronic total coronary occlusion and the risk of ventricular tachyarrhythmic events in out-of-hospital cardiac arrest survivors.

IntroductionChronic total coronary occlusion (CTO) has been identified as a risk factor for ventricular arrhythmias, especially a CTO in an infarct-related artery (IRA). This study aimed to evaluate the effect of an IRA-CTO on the occurrence of ventricular tachyarrhythmic events (VTEs) in out-of-hospital cardiac arrest survivors without ST-segment elevation.MethodsWe conducted a post hoc analysis of the COACT trial, a multicentre randomised controlled trial. Patients were included when they survived index hospitalisation after cardiac arrest and demonstrated coronary artery disease on coronary angiography. The primary endpoint was the occurrence of a VTE, defined as appropriate implantable cardioverter-defibrillator (ICD) therapy, sustained ventricular tachyarrhythmia or sudden cardiac death.ResultsA total of 163 patients from ten centres were included. Unrevascularised IRA-CTO in a main vessel was present in 43 patients (26%). Overall, 61% of the study population received an ICD for secondary prevention. During a follow-up of 1 year, 12 patients (7.4%) experienced at least one VTE. The cumulative incidence rate of VTEs was higher in patients with an IRA-CTO compared to patients without an IRA-CTO (17.4% vs 5.6%, log-rank p = 0.03). However, multivariable analysis only identified left ventricular ejection fraction < 35% as an independent factor associated with VTEs (adjusted hazard ratio 8.7, 95% confidence interval 2.2–35.4). A subanalysis focusing on CTO, with or without an infarct in the CTO territory, did not change the results.ConclusionIn out-of-hospital cardiac arrest survivors with coronary artery disease without ST-segment elevation, an IRA-CTO was not an independent factor associated with VTEs in the 1st year after the index event.Supplementary InformationThe online version of this article (10.1007/s12471-021-01578-3) contains supplementary material, which is available to authorized users.

Concealed cardiomyopathy as a frequent cause of idiopathic ventricular fibrillation in a representative Czech cohort of survivors of sudden cardiac arrest (SCA)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic Introduction The complex diagnostic work up in SCA survivors often does not yield a concrete cardiological diagnosis. Moreover, there is conflicting evidence whether genetic testing could support or guide clinical diagnostics. Purpose To assess the molecular architecture of idiopathic ventricular fibrillation in cases without apparent evidence of specific structural or arrhythmic cardiac disease at initial diagnostic work up in a representative Czech cohort. Patients and Methods Between 2013 - 2020 we have ascertained 100 SCA survivors (54 M / 46 F; age range at cardiac arrest 5-69 years). Genetic counselling was followed by massively parallel DNA sequencing using custom-made panels comprising 100 cardiac conditions-related genes. Subsequently, thorough cardiological screening examinations in first degree relatives were carried out. Presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results Highly likely or certain molecular aetiology (i.e. based on the presence of Class 4 or 5 variants) was disclosed in 20/100 (20%) in PKP2 (3x), SCN5A (4x), RYR2 (3x), TTN (2x), PLN, FLNC, PRKAG2, KCNH2, KCNQ1, SLC4A, TNNT2, and DSP. Interestingly, the KCNE1 p.Asp85Asn (LQT 5 lite) variant, was detected in further 3/100 cases, representing a recognized risk factor for ventricular arrhythmias. Conclusions Genetic testing facilitates stratification of the cause of arrhythmia in a substantial portion of SCA survivors. The utility of positive outcomes of genetic testing was substantiated in 10/20 gene positive patients, where the genetic stratification led to diagnosis of concealed arrhythmogenic cardiomyopathy, whose extent of morphological changes was under the diagnostic sensibility of imaging modalities or ECG. Our results enable individualized care in SCA survivors and assure targeted preventive approaches in their relatives.

Prolonged QTc Interval in Nigerian Children with Sickle Cell Anemia

Prolonged QTc interval, a risk factor for ventricular arrhythmia, occurs in sickle cell anemia. The aim of this study was to determine the risk of prolonged QTc interval and its relationship with vaso-occlusive painful crises (VOCs) and follow-up steady-state in the same children with sickle cell anemia. This prospective cohort study enrolled 38 subjects, aged 5–17 years. History of bone pain and examination were obtained during VOC and steady-state. Assessment of QTc interval was with 12-lead electrocardiography. The QTc interval value >0.440 seconds was taken as prolonged. Median (interquartile range) of QTc interval was higher during VOC [0.447 (0.438–0.459) seconds] than during steady-state [0.435 (0.417–0.440) seconds]. Risk of prolonged QTc interval was higher during VOC (68.4%) than in steady-state (21.1%) with relative risk of 3.250 [95% confidence interval (CI) = 1.692–6.241]. Prolonged QTc interval was likely to occur [area under curve (AUC) = 0.759, p<0.001] during VOC with 68.4% sensitivity, 78.9% specificity and at cutoff point of 0.441 seconds. Prolonged QTc interval negatively correlated with packed cell volume (PCV) during VOC [rs (36) = −0.14, p = 0.387]. Binary logistics of the combined effect of PCV and gender on QTc interval showed that during VOC, males were more likely to have prolonged QTc [odds ratio (OR): 1.337 (95% CI: 0.327–5.464; p = 0.686]. Children with sickle cell anemia, particularly males, were three-times more likely to have prolonged QTc interval during VOC when QTc interval was >0.441 seconds. Routine electrocardiography may help to identify those with QTc intervals above this threshold for prompt cardiac-oriented management.

Knockout of interleukin-17A diminishes ventricular arrhythmia susceptibility in diabetic mice via inhibiting NF-κB-mediated electrical remodeling.

Interleukin-17A (IL-17), a potent proinflammatory cytokine, has been shown to participate in cardiac electrical disorders. Diabetes mellitus is an independent risk factor for ventricular arrhythmia. In this study, we investigated the role of IL-17 in ventricular arrhythmia of diabetic mice. Diabetes was induced in both wild-type and IL-17 knockout mice by intraperitoneal injection of streptozotocin (STZ). High-frequency electrical stimuli were delivered into the right ventricle to induce ventricular arrhythmias. We showed that the occurrence rate of ventricular tachycardia was significantly increased in diabetic mice, which was attenuated by IL-17 knockout. We conducted optical mapping on perfused mouse hearts and found that cardiac conduction velocity (CV) was significantly decreased, and action potential duration (APD) wasprolonged in diabetic mice, which were mitigated by IL-17 knockout. We performed whole-cell patch clamp recordings from isolated ventricular myocytes, and found that the densities of Ito, INa and ICa,L were reduced, the APDs at 50% and 90% repolarization were increased, and early afterdepolarization (EAD) was markedly increased in diabetic mice. These alterations were alleviated by the knockout of IL-17. Moreover, knockout of IL-17 alleviated the downregulation of Nav1.5 (the pore forming subunit of INa), Cav1.2 (the main component subunit of ICa,L) and KChIP2 (potassium voltage-gated channel interacting protein 2, the regulatory subunit of Ito) in the hearts of diabetic mice. The expression of NF-κB was significantly upregulated in the hearts of diabetic mice, which was suppressed by IL-17 knockout. In neonatal mouse ventricular myocytes, knockdown of NF-κB significantly increased the expression of Nav1.5, Cav1.2 and KChIP2. These results imply that IL-17 may represent a potential target for the development of agents against diabetes-related ventricular arrhythmias.

Mitral annulus disjunction as an incremental risk factor for ventricular arrhythmia in young patient.

Mitral annulus disjunction as an incremental risk factor for ventricular arrhythmia in young patient.

Impact of pregnancy and risk factors for ventricular arrhythmias in women operated for tetralogy of Fallot

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority Background Patients with tetralogy of Fallot (TOF) have a high survival rate 30 years after surgical repair, and generally enjoy a satisfactory quality of life. Many female patients experience pregnancy during adulthood, however the effects of pregnancy on the long-term cardiovascular outcome in this group of patients are not well known. Purpose We aimed to investigate the association of pregnancy and cardiac function with occurrence of ventricular arrhythmia (VA) in women operated for TOF. Methods We included 80 patients recruited from the national database for patients diagnosed for TOF. All were examined with echocardiography, including strain echocardiography. We assessed mechanical dispersion of right ventricle (RV) as measure of heterogeneous contraction. Holter monitoring or implanted devices detected ventricular arrhythmias (VA), defined as non-sustained or sustained ventricular tachycardia or aborted cardiac arrest. Blood tests included N-terminal pro-brain natriuretic peptide (NT-proBNP). Results In all, 55 (69%) women had experienced pregnancy (age 40 ± 9 years, parity median 1, range 1-4), while 25 (31%) women were nulliparous. The mean age was lower in nulliparous compared to those with children (30 ± 9 vs 40 ± 9, p &amp;lt; 0.01). VA was more prevalent in women who had experienced pregnancy (n = 16, 94%) compared to nulliparous (n = 1, 6%) (p = 0.02), and importantly also when adjusted for age [adjusted OR 9.8 (95% CI 1.2-79.1), p = 0.02]. RV mechanical dispersion was more pronounced in patients with VA [39.2 ± 14 ms vs. 49.6 ± 8 ms, p = 0.009, adjusted OR 2.1 (95% CI 1.3 - 7.5), p = 0.01 adjusted for age]. Higher NT-proBNP was also a marker of VA [211 ng/L (127-836) vs. 139 ng/L (30-465), p = 0.007, adjusted OR 1.4 (95% CI 1.1 - 1.8) p = 0.017 adjusted for age]. NT-proBNP &amp;gt;182 ng/L (normal values &amp;lt; 170 ng/L) optimally detected women with VA (p = 0.019), also independent of age [OR 7.2 (95% CI 1.7-30.1), p = 0.007]. Conclusion History of pregnancy was associated with higher prevalence of VA among women with surgically corrected TOF. Right ventricular mechanical dispersion and NT-proBNP were age independent markers of VA. These findings may have importance for risk stratification and preconception counselling of these patients.

Territory-Wide Chinese Cohort of Long QT Syndrome: Random Survival Forest and Cox Analyses.

Introduction: Congenital long QT syndrome (LQTS) is a cardiac ion channelopathy that predisposes affected individuals to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD). The main aims of the study were to: (1) provide a description of the local epidemiology of LQTS, (2) identify significant risk factors of ventricular arrhythmias in this cohort, and (3) compare the performance of traditional Cox regression with that of random survival forests.Methods: This was a territory-wide retrospective cohort study of patients diagnosed with congenital LQTS between 1997 and 2019. The primary outcome was spontaneous VT/VF.Results: This study included 121 patients [median age of initial presentation: 20 (interquartile range: 8–44) years, 62% female] with a median follow-up of 88 (51–143) months. Genetic analysis identified novel mutations in KCNQ1, KCNH2, SCN5A, ANK2, CACNA1C, CAV3, and AKAP9. During follow-up, 23 patients developed VT/VF. Univariate Cox regression analysis revealed that age [hazard ratio (HR): 1.02 (1.01–1.04), P = 0.007; optimum cut-off: 19 years], presentation with syncope [HR: 3.86 (1.43–10.42), P = 0.008] or VT/VF [HR: 3.68 (1.62–8.37), P = 0.002] and the presence of PVCs [HR: 2.89 (1.22–6.83), P = 0.015] were significant predictors of spontaneous VT/VF. Only initial presentation with syncope remained significant after multivariate adjustment [HR: 3.58 (1.32–9.71), P = 0.011]. Random survival forest (RSF) model provided significant improvement in prediction performance over Cox regression (precision: 0.80 vs. 0.69; recall: 0.79 vs. 0.68; AUC: 0.77 vs. 0.68; c-statistic: 0.79 vs. 0.67). Decision rules were generated by RSF model to predict VT/VF post-diagnosis.Conclusions: Effective risk stratification in congenital LQTS can be achieved by clinical history, electrocardiographic indices, and different investigation results, irrespective of underlying genetic defects. A machine learning approach using RSF can improve risk prediction over traditional Cox regression models.

Impact of pregnancy and risk factors for ventricular arrhythmias in women with tetralogy of Fallot

ObjectivePatients with tetralogy of Fallot (TOF) have high survival rates 30 years after surgical repair. Many patients experience pregnancy; however, the effects of pregnancy on the long-term cardiovascular outcome are...

Arrhythmic phenotypes in patients with left ventricular non-compaction cardiomyopathy

Abstract Background Identification of pts with left ventricular non-compaction cardiomyopathy (NCCM) at high risk of life-threatening arrhythmic events is focused on clinical and instrumental criteria. The genetic component is not taken into account when deciding on a strategy for preventive measures. Purpose To analyze life-threatening arrhythmic events in pts with the arrhythmic variant of NCCM and to identify genetic factors that may increase the risk of life-threatening arrhythmic events. Methods The study included 159 pts, among whom 58 had malignant ventricular arrhythmias (mean age 43.54±11.95 years, 34/24/58.6% male). The NCCM criteria were confirmed using Echocardiography and CMR. Mutation search was carried out by the next generation sequencing (NGS) in 21 pts with nonsustained ventricular tachycardia (NVT). Results During the follow-up period (median follow-up of 36 months), life-threatening arrhythmic events (documented sustained VT, SCD with successful resuscitation and CD implantation, SCD) were registered in 29 pts (50%), and 10 pts had CD implanted. As a result of sequencing, 23.8% (5 out of 21) of pts with NVT revealed rare genetic variants with uncertain clinical significance (VUS) in 3 genes encoding ion channel proteins: KCNQ1, KCNH2 (9.5%), RYR2 (9.5%). In 9 (42.9%) pts, 10 identified mutations were localized in the genes responsible for the synthesis of sarcomeric proteins: MYBPC3 (23.8%), MYH7 (23.8%). 12 genetic variants were found in overlapping phenotypes between NCCM, ARVC and DCM: PKP2, DSP, PLN, TRPM4 (14.3%), RBM20, LDB3 (9.5%), DPP6, DTNA, NEXN in 11 (52.4%) pts. In this group of pts, the most common (81.8% of cases) were life-threatening arrhythmic events that required surgical intervention: 6 pts were implanted with CD for primary prevention of SCD, two pts - CRT-D, two pts with systolic dysfunction were performed with OHT and one patient was implanted with the Accucinch transcatheter direct mitral valve annuloplasty system. In pts with mutations in sarcomeric protein genes, CD was implanted in 4.7% of cases, and in 14.3% of pts with mutations in ion channel genes (p&amp;lt;0.01). Conclusion The presence of mutations in genes that control the functioning of ion channels in complex overlapping genotypes is an additional risk factor for ventricular arrhythmias in patients with NCCM. Determining the genetic component opens up new opportunities for personalizing the risk stratification of pts with NCCM. Funding Acknowledgement Type of funding source: None