Risk Of VT Research Articles

A case involving tooth extraction of upper and lower third molars under general anesthesia in a patient with catecholaminergic polymorphic ventricular tachycardia

AbstractBackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT), an inheritable arrhythmia, poses a grave risk of syncope or cardiac arrest.Case PresentationA 23‐year‐old female with CPVT history and implantable cardioverter‐defibrillator (ICD) implantation sought tooth extraction of her third molars. She underwent the procedure under general anesthesia to mitigate VT risk. Defibrillation function was temporarily halted during anesthesia induction, managed with total intravenous anesthesia. The postoperative course remained uneventful, obviating defibrillation intervention.ConclusionsThis case underscores the efficacy of general anesthesia in averting VT onset during oral surgery for CPVT patients, ensuring a safe and uneventful postoperative recovery.

LGE in CMR and outcomes in cardiac sarcoidosis

Abstract Background Late-gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a predictor of adverse events in patients with cardiac sarcoidosis (CS). This meta-analysis evaluated the correlation between LGE and mortality, ventricular arrhythmias (VA), sudden cardiac death (SCD), and heart failure (HF) outcomes. Methods A literature search was conducted for studies reporting the association between LGE in CS and the study endpoints. The endpoints are: mortality, VA and SCD, and HF hospitalization. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow-up duration was one year. Results A total of 17 studies and 1,915 CS patients (595 with LGE vs 1,320 without LGE) were included; mean follow-up was 3.3 years (ranging between 17 to 84 months). LGE was associated with increased all-cause mortality (OR 6.05, 95% CI 3.16-11.58; P<0.01), cardiovascular mortality (OR 5.83, 95% CI 2.89-11.77; P<0.01) and VA and SCD (OR 16.48, 95% CI 8.29-32.73; P<0.01). The presence of LGE in the right ventricle is associated with higher risk of VT (OR 6.11, 95% CI 1.14-32.68; P 0.035). LGE was associated with an increased risk of HF hospitalization (OR 17.47, 95% CI 5.54-55.03; P<0.01). Conclusion LGE in CS patients is associated with increased mortality, VA and SCD, and HF hospitalization during long-term follow up. The presence of LGE in the right ventricle is associated with higher risk of VT.

Vascular thrombosis after pediatric liver transplantation: Is prevention achievable?

BackgroundVascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric studies are lacking. MethodsThis multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications. ResultsWithin seven postoperative days, 31/331 (9.37%) patients developed intra-abdominal VT. Open fascia occurred more commonly in patients with VT (51.61 vs 23.33%) and remained the only independent risk factor in multivariable analysis (OR = 2.84, p = 0.012). Patients with VT received more blood products (83.87 vs 50.00%), had significantly higher rates of graft loss (22.58 vs 1.33%), infection (50.00 vs 20.60%), and unplanned return to the operating room (70.97 vs 16.44%) compared to those without VT. The risk of bleeding was similar (p = 0.2) between patients on and off anticoagulation. ConclusionsProphylactic anticoagulation did not increase bleeding complications in this cohort. The only independent factor associated with VT was open fascia, likely a graft/recipient size mismatch surrogate, supporting the need to improve surgical techniques to prevent VT that may not be modifiable with anticoagulation.

The effectiveness and safety of blood flow restriction training for the post-operation treatment of distal radius fracture

Introduction Distal radius fracture (DRF) is a common injury in the upper extremities. Blood flow restriction (BFR) has been proven to be effective in improving function in low-load training, which is suitable for post-op rehabilitation. We explored the effectiveness and safety of BFR therapy in DRF patients who underwent surgery. Materials and methods Thirty-five patients were randomly assigned to either the BFR or the regular training (RT; no BFR therapy) groups. All patients completed the same 4-week postoperative rehabilitation program, including anti-inflammatory treatments, strengthening and range of motion (ROM) training. In the BFR group, the pressure was 120 mmHg in strengthening training course. Pain, circumferences of wrists and forearms, ROM, muscle strength, and D-dimer levels were evaluated at weeks 0, 2, and 4. Radius union scoring system (RUSS) was measured at weeks 4 and 12. Finally, wrist functionality (Cooney modification) was evaluated at week 12. Results The BFR group had significantly decreased pain levels compared with the RT group (p < 0.01, effect size= 2.33, −2.44 at weeks 2 and 4). Swelling was effectively relieved in both groups. The wrist swelling was less in the BFR group (p < 0.01, effect size = −2.17 at week 4). The isometric strength of wrist extension (p < 0.01, effect size = 1.5, 3.02 at weeks 2 and 4), flexion (p < 0.01, effect size = 1.33, 2.53 at weeks 2 and 4), and functionality significantly increased in the BFR group (p < 0.01, effect size = 2.80 at week 12). No risk of VT in the BFR group was found. BFR did not threaten bone healing. Conclusions In patients with DRF who underwent corrective surgery, BFR therapy effectively relieved pain and swelling, increased muscle strength and wrist function, and had no additional risks for bone healing and VT.

PO-05-161 ACQUIRED LONG QT SYNDROME IN SEPSIS-INDUCED MYOCARDIAL INJURY: INVESTIGATION ON CLINICAL CHARACTERISTICS AND MECHANISM VIA ION CHANNEL REPROGRAMMING

Sepsis-induced cardiomyopathy (SIC) is one major cause of death in sepsis. Evidence of various cardiac arrhythmias in septic patients has been reported previously. Acquired QT prolongation (aQTP) is associated with an increased risk of polymorphic VT and Torsade de Pointes. However, data on the clinical analysis of aQTP, or acquired long QT syndrome (aLQTS) in sepsis and their potential mechanism is limited. We aimed to investigate the prevalence and characteristics of aQTP/aLQTS in sepsis and explore the underlying mechanism. Patients diagnosed with sepsis from 2018 to 2022 were enrolled. Occurrence of aQTP as well as cardiac arrhythmias were described. Correlation analysis was performed to investigate associated factors, followed analysis on prognosis. Mouse model for SIC was thereafter established, in which bulk-RNA sequencing of the heart was performed. The gene expression of myocardial tissue was then determined by RT-quantitative polymerase chain reaction. Biostatistical analysis based on Gene Expression Omnibus database were performed. Among 110 patients diagnosed with sepsis, aQTP was found in 13 (11.8%) subjects with a mean QTc of 502 msec, in which 2 typical aLQTS cases with progressive QTP was observed to develop electrical storm during sepsis following pacemaker implantation and esophagectomy, respectively. In correlation analysis, the prevalence of aQTP was found statistically associated with heart failure (p=0.009) and all-cause shock (p=0.02). As for primary endpoints, aLQTS was shown relevant with the length of ICU stay (p=0.037) and as an independent risk factor for all-cause death (p=0.026) in sepsis. Sequencing of myocardium on SIC mice revealed multiple genes associated with electrical ion channels were significantly altered in SIC, e.g., KCNQ1 (p<0.001, R2=0.84), KCNJ5(p<0.001, R2=0.97), SCN5A (p<0.001, R2=0.86), CALMl4 (p-0038, R2=0.36) etc., which affect cardiac repolarization by regulating potassium, sodium and calcium channels, and was in accordance with the results of qPCR for the hub genes. Externally validation based on GEO database demonstrated similar results. aQTP is not infrequently observed in sepsis-induced myocardial injury, which is associated with poor prognosis in septic patients. It requires more clinical awareness of regular monitoring for related aLQTS and other complications. Sepsis-induced myocardial inflammation may have an impact on the expression of multiple genes related to myocardial repolarization.

JS-NG-8: CASE REPORT: POSSIBLE NEW CHANNELOPATHY ASSOCIATED WITH ELEVATED ALDOSTERONE LEVELS

Background: Potassium channelopathies are associated with prolonged QT cardiac syndrome. New potassium channelopathies in somatic cells, including KCNJ5 mutations, also underlie some forms of primary hyperaldosteronism. We present a first-in-human report of an association between a KCNQ1 loss of function mutation manifesting with life threatening-ventricular tachycardia (VT), severe hypokalemia and presumed hyperaldosteronism. Case Presentation: The patient is a 51-year-old Asian woman known for obesity, Wolff-Parkinson-White post ablation, and recurrent syncopal episodes with polymorphic VT due to prolonged QTc, requiring an implantable cardioverter defibrillator. On initial presentation for syncope, spontaneous hypokalemia was discovered at 3.1 mmol/L. She had multiple hospitalizations for torsade storms and persistent hypokalemia resistant to aggressive potassium supplementation until addition of spironolactone. Investigations revealed a suppressed plasma renin activity &lt; 0.05 ng/L/s, serum aldosterone concentration at 302 pmol/L, and an aldosterone to renin ratio (ARR) &gt; 6040. Repeated ARR was &gt; 10980. Confirmatory saline suppression testing or adrenal vein sampling were not performed due to risk of recurrent VT associated with spironolactone cessation. A comprehensive evaluation for the etiology of this patient's clinical presentation revealed a mutation in the KCNQ1 gene type 1. Literature review: The voltage-dependent K(+) channel responsible for activating delayed K(+) current is composed of pore-forming KCNQ1 and regulatory KCNE1/3 subunits which loss of function predispose to sustained torsade de pointes. Animal models demonstrate that KCNQ1 and KCNE1 mRNAs are expressed in the zona glomerulosa of adrenal glands where potassium channels directly participate in the control of aldosterone production. Although KCNE3 is not expressed in mouse adrenals, its deletion is thought to cause activation of lymphocytes targeting adrenal glands, leading to hyperaldosteronism. Furthermore, administration of spironolactone to KCNE3 knockout mice ameliorates their QT prolongation and predisposition to VT. There have been no case reports of an association between KCNQ1/E1/E3 loss of function and hyperaldosteronism in humans. Conclusion: This raises the question if this mechanism can also be a component of human KCNQ1 and KCNE1/3-linked arrhythmogenesis and hyperaldosteronism. Alternatively, we can further speculate that patients with hyperaldosteronism who develop malignant arrhythmias during hypokalemia are subjects with impaired repolarization reserve as a consequence of variants in genes known to cause long QT syndrome. The variants, leading to subclinical ion channel dysfunction, are typically silent until unmasked by electrolytes abnormalities such as hypokalemia. To our knowledge, this case is a first report of a potentially novel channelopathy associated with hyperaldosteronism in humans. These findings are hypothesis generating and require further investigations.

RISKS OF MOTHER-TO-CHILD TRANSMISSION OF HIV

Vertical transmission is a condition in which the virus is infected from mother to child and can have some consequences and risks during pregnancy and at the time of delivery. It is estimated that the incidence of vertical transmission occurs in 25% of pregnancies of infected women when there are no prophylactic measures and therapeutic interventions, resulting in high rates of mortality and disease progression. Contact with contaminated fluids can lead children to contract the virus in the first few months of life. The factors involved include several failures in the health system and maternity. Thus, the present study is based on the following justification: In health services and in the social context, there are difficulties and gaps that contribute to the risk factors of vertical transmission of HIV, constituting negative results for the control of the disease. In view of this, the objective of this research is to identify in the literature which are the existing difficulties that influence the prophylactic measures of vertical transmission. This study was carried out through an integrative literature review, through a survey of data in the scientific bases: LILACS, SCIELO and BDENF. The results obtained indicate that the failure to take prophylactic measures during pregnancy, due to negligence in prenatal consultations, is considered one of the aggravating factors for the risk of VT. Without early diagnosis, without knowledge of the virus, the pregnant woman does not undergo treatment with antiretroviral medication, with this, the immune system is more vulnerable to weakening and risks of complications during pregnancy.&#x0D;

Ventricular tachycardia mechanisms and prevention in patients with severe heart failure and left ventricular assist device

Abstract Terminal Heart Failure with reduced Ejection Fraction (HFrEF) is associated with severe morbidity and mortality. Mechanical Left Ventricular Assist Devices (LVAD) are often used to provide these patients with a last resort therapy and as bridge to transplant. However, HFrEF patients with LVAD have significant myocardial substrate for ventricular arrhythmias and the LVAD itself might be regarded as pro-arrhythmogenic. Aim of the current study was to investigate the mechanism of ventricular arrhythmias in LVAD patients and to provide evidence for the hypothesis that ad-hoc ablation/substrate modification during surgical LVAD implantation might reduce the risk of VT. We retrospectively analyzed invasive ablation procedures in patients with VT±LVAD and determined the mechanism of arrhythmia during electrophysiological examination (using 3D electroanatomical and local activation time mapping; Carto; Biosense Webster) in LVAD (n=17) and non-LVAD (n=12) subgroups. Mean age of the predominantly male (97%) patients was 60±2 years. VTs were directly LVAD associated (i.e. focal, adjacent to LVAD insertion or macro-reentry, around LVAD) in almost half of the LVAD patients. Number of radiofrequency ablation (RF) lesions and RF time were not significantly different between LVAD associated VT and non-LVAD associated VT patients. Within the LVAD patient group, freedom from VT (mean follow-up 40±6 months) was 50% upon ablation in patients with VTs originating from the LVAD region and 70% if ablation was conducted in non-LVAD regions. None of the LVAD associated and 22% of non-LVAD associated VT patients died during follow-up of these critically ill patients. Moreover, to reduce LVAD related arrhythmias and based on additional ex-vivo/in-silico derived data, we propose a distinctive (i.e. “star” shaped, LVAD encirclement) epicardial substrate modification during surgical LVAD implantation. In summary, a significant percentage of patients with LVAD exhibit LVAD-associated focal/macro-reentry VT and recurrence rates are high. VT likelihood is reduced ex-vivo/in-silico upon substrate modification targeting myocardium adjacent to a possible LVAD implantation site. Epicardial RF ablation during surgical LVAD implantation might allow prevention of LVAD-associated focal/macro-reentry VT. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence

BackgroundThe World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers’ ART adherence may be suboptimal. We evaluate the inclusion of the mothers’ self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers’ VL result is not available at delivery.MethodsWe used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers’ adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%.ResultsAt delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants.ConclusionsIn the absence of a VL result, mothers’ self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

MO245: Risk Factors for Venous Thrombosis in ANTI-PLA2R + VE AND−VE Primary Membranous Nephropathy: A 6-YEAR Retrospective Analysis

Abstract BACKGROUND AND AIMS Venous thrombosis (VT) is an established cause of increased morbidity and mortality amongst patients with nephrotic syndrome. Previous studies suggest primary membranous nephropathy (PMN) to be associated with the highest risk of developing VT amongst all nephrotic diseases. Antibodies to the phospholipase A2 receptor (anti-PLA2R) is identified as a pathogenic marker to the disease activity of PMN, and considered a strong prognostic marker toward disease progression and treatment response. Recent evidence cites the potential of anti-PLA2R as an independent risk factor of VT in PMN. Nevertheless, the pathophysiology of VT for anti-PLA2R + ve and –ve PMN is not fully known. Whether the common risk factors of VT remain as significant within the anti-PLA2R + ve and –ve PMN context is also not convincingly elucidated of yet. Our study aimed to evaluate and compare risk factors for VT in patients with anti-PLA2R + ve and –ve PMN. METHOD This is a retrospective analysis of patients diagnosed with PMN between October 2015 and September 2021. Patients included are age ≥18 years, have biopsy-diagnosed PMN and anti-PLA2R direct immunofluorescence assay testing following PMN diagnosis. Patients excluded were those with secondary causes of membranous nephropathy, history of previous immunosuppression, kidney transplantation before or following PMN diagnosis, or where iatrogenic causes such as major surgery or prolonged immobilization led to VT. Study patients were screened until 28 November 2021 for any VT event and were grouped between those with anti-PLA2R + ve and −ve test results. Demographic and clinical parameters from age, gender, presence of co-morbidities and common risk factors associated with increased risk of VT (hypertension, diabetes mellitus, atrial fibrillation, CHA2DS2-VASC ≥ 3, BMI &amp;gt;30, malignant disease, hormonal treatment and contraceptive pill use), serum and urine biochemical test results at PMN diagnosis (albumin, 24-h proteinuria, proteinuria/albumin ratio, creatinine, eGFR, cholesterol, triglycerides and IgG) were collected. The comparison of demographic and clinical parameters for patients with and without VT in each of the anti-PLA2R + ve and –ve groups was conducted through chi-squared, t and Mann–Whitney U tests. Multivariate regression analysis determined the significance of association between each parameter and VT event occurrence. RESULTS Seventy patients with PMN were included in this study, of which 39 patients are anti-PLA2R + ve and 31 patients are anti-PLA2R−ve. Eight patients (20.5%) had VT in the anti-PLA2R + ve group during follow-up whilst this was the case for four patients (12.9%) in the anti-PLA2R−ve group. In both groups, patients with VT were found to have higher serum cholesterol levels (P &amp;lt; 0.05). Lower serum albumin levels, and greater 24-h proteinuria and proteinuria/albumin ratio was observed in patients with VT within the anti-PLA2R−ve group (P &amp;lt; .05). Full results from the multivariate regression analysis are presented in Tables 1 and 2. Serum cholesterol is demonstrated to be significantly associated with VT in the anti-PLA2R + ve (OR 1.42, 95% confidence interval (CI) 1.12–1.72) and anti-PLA2R−ve groups (OR 1.45, 95% CI 1.15–1.76), respectively. Serum albumin (OR 0.72, 95% CI 0.49–0.96), 24-h proteinuria (OR 1.33, 95% CI 1.03–1.63) and proteinuria/albumin ratio (OR 1.32, 95% CI 1.04–1.59) are shown to be significantly associated with VT within the anti-PLA2R−ve group. CONCLUSION There is supporting evidence that serum cholesterol, albumin and proteinuria may all present as important markers of risk prediction for VT in patients with PMN, though this will require further validation in prospective multi-center studies with larger patient samples. Close monitoring of these markers, and early intervention in response to hypercholesterolemia, hypoalbuminemia and proteinuria with consideration of anti-PLA2R status should ensue as part of primary prevention strategies to reduce VT incidence in the PMN population.

The mitral annulus disjunction of mitral valve prolapse: Presentation and outcome

To assess in MVP-patients, MAD prevalence, phenotypic characteristics and long-term outcome. A cohort of 595 (278 female, age 61 ± 16 years) consecutive patients with isolated MVP, comprehensive clinical, rhythmic, Doppler-echocardiographic and consistent MAD assessment, was examined. MAD prevalence, associated MVP-phenotype and outcome [survival, ventricular arrhythmias (VA)] were analyzed. To balance important baseline differences, we also propensity score matched patients with and without MAD (no-MAD). MAD presence was common (186 – 31%) in MVP, generally in younger patients and was not random but independently associated with severe myxomatous disease and larger left ventricle ( P ≤ 0.005). Age-matched-cohort survival after MVP diagnosis was not worse with MAD (10-year 93 ± 2% for no-MAD and 97 ± 1% for MAD, P = 0.4), even adjusted-comprehensively for MVP characteristics ( P = 0.8) and accounting for time-dependent mitral-surgery ( P = 0.6). During follow-up, 218 patients were diagnosed with VA post-30 days from MVP diagnosis (159 with ventricular tachycardia-VT). MAD was independently associated with higher risk of VA (adjusted-hazard-ratio 2.39[1.79–3.22]) and VT (2.79[1.98–3.94], both P < 0.0001). MAD link to VA persisted with time-dependent mitral-surgery (adjusted-hazard-ratio 2.25[1.65–3.01], P < 0.0001), strongly under medical-management (adjusted-hazard-ratio 2.91[1.95–4.35], P < 0.0001) but weakly post-mitral-surgery (adjusted-hazard-ratio 1.77[1.12–2.79], P = 0.01). This large cohort with MVP comprehensively characterized, shows that MAD is frequent at MVP diagnosis and strongly linked to advanced-myxomatous-degeneration. MAD presence is independently associated with long-term excess-incidence of VA and VT. However, within the first 10 years post-diagnosis MAD is not linked to excess-mortality and while reassurance should be provided from the survival point of view careful monitoring for arrhythmias is in order with MAD.

Procoagulant factor levels and risk of venous thrombosis in the elderly

Unlabelled Box AbstractBackgroundVenous thrombosis (VT) incidence increases markedly with age. Coagulation factors are also positively associated with age. ObjectiveTo study whether higher levels of coagulation factors II (prothrombin), VIII, IX, and XI are associated with risk of a first VT in the elderly. MethodsFour hundred and one patients and 431 control subjects aged 70 and older were included in the Age and Thrombosis, Acquired and Genetic risk factors in the Elderly (AT‐AGE) study. Blood was collected 1 year after the event in patients and in all control subjects for measurement of coagulation factors. To assess the risk of VT, odds ratios (ORs) were calculated after stratification of coagulation factors in quartiles and at the 90th percentile, adjusting for potential confounders (age, sex, body mass index, and study center). ResultsMean age was 78 years (range: 70‐100 years). The ORs of VT for factors in the top quartile compared with the lowest quartile were 4.5 (95% confidence interval [CI]:2.7‐7.3) for factor VIII, 2.4 (95% CI:1.1‐5.2) for factor IX, and 1.7 (95% CI:1.0‐2.9) for factor XI. High prothrombin was not associated with an increased VT risk. There was no dose‐response association between the number of high coagulation factors and VT risk. The population attributable risk (PAR) of VT was 37.6%, 23.3%, and 12.4% for factor VIII, IX, and XI, respectively. ConclusionIn this study of the elderly, higher factors VIII, IX, and XI but not prothrombin, were positively associated with the risk of VT.

Abstract 14047: Novel Noninvasive Risk Stratification Method Using Control-and-stability-theory Applied to 12-lead-ECG Repolarization Patterns in Brugada Type1 Subjects

Background: Brugada syndrome (BrS) risk stratification in asymptomatic subjects and its underlying pathophysiological dynamics is complex. Purpose: This study aims to analyze, from alternative standpoints, superficial 12-lead ECG V2 repolarization patterns (repol.). This method diverges from ECG pattern characterization (patterns, angles, shapes, intervals, waves); it rather exploits nonlinear dynamics and stability of ECG repol. to assess stability driving cardiac dynamics: basal, after flecainide, during RF ablation, after 2nd flecainide test and post procedure. Target: to lower the number of invasive electrophysiology studies, furthering knowledge and applications of control-and-stability-theory applied to ECG. Methods: A stability control closed loop system has been designed to model electrophysiology dynamics of cardiac conduction: ECG segments being the input-output of the system. (Figure). A sequence of V2 repol. have been scanned, digitized and quantitatively processed yielding stability parameters (poles in S-plane). Scanning by Digitizeit - Digital River GmbH. S-plane computation by Microsoft Office, Wolfram Demonstrations Project &amp; Contributors, https://demonstrations.wolfram.com Results: Figure. Conclusions: Based on our data, 1) 12-lead-ECG repol. are associated with increasing stability (parameter values b), denoting underlying nonlinear dynamics, trending to incremental stability from basal to end of procedure.2) The incremental stability associated with all the process phases, from basal to end of procedure, indicates a potential use of this methodology to BrS risk stratification. Unstable repol. may be classified as high VT risk. In conclusion, furthering control-and-stability-theory applied to 12-lead ECGs aims to deeper comprehension of physiological and pathological substrates of malignant arrhythmias, and to focus on noninvasive risk stratification strategies for ICD implantation indication in BrS.

129Magnetic resonance predictors of ventricular tachycardia recurrence after radiofrequency substrate ablation: septal and transmural channels

Abstract Ventricular tachycardia (VT) substrate-based ablation has become a gold standard in patients with structural heart disease. Success of VT ablation is related with mortality reduction. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is a powerful technique to assess substrate of VT. Myocardial fibrosis is electrically inert (Core) but it is surrounded by a ‘‘border-zone (BZ)’’ where normal cardiomyocytes intermingle with dense bundles of fibrosis. Slow impulse conduction in the BZ allows for the re-entry circuits leading to VT. Both the presence and extent of LGE have been associated with VT and SCD risk. LGE-CMR tissue characterization can be depicted as pixel signal intensity (PSI) maps and can guide VT ablation. The aim of this study was to analyze possible VT recurrence predictors in a long term follow-up of patients that underwent VT ablation (endo and/or epicardial) related with LGE-CMR PSI maps. We analyzed 234 consecutive patients (age: 63.2 ± 14 years, follow-up: 3.14 years ±1.8) undergoing VT ablation with scar-dechannelling technique at a single center from 2013 to 2018. 110 patients underwent a preprocedural LGE-CMR, and in 94 patients (85,5%) a CMR-aided ablation using the PSI maps was performed. All LGE-CMR images were semi-automatically processed using a dedicated software. PSI-based algorithm was applied to characterize the hyperenhanced area as core or BZ, using fixed threshold of the maximum intensity. A LV 3D shell was obtained and were imported into the navigation system. In the PSI maps, heterogenous tissue channels were defined as a continuous corridor of BZ surrounded by scar core or an anatomic barrier that connects 2 areas of healthy tissue. Results Overall recurrence of VT was 41.8 %. There was ICD shock reduction, from 43,6% to a 28,2% (ICD shocks before ablation 2,23 ± 7,32, after: 1,10 ± 2,92). Left ventricle mass predicted significantly VT recurrence (Mean 168,3 ± 53,3 vs 152,3 ± 46,4 g, HR 1,02 [1,01-1,02], p &amp;lt; 0.001). LGE distribuition was predictive of VT recurrence when a more than 40% of the interventricular septum was involved (62,5% vs 37,8%; HR 1,6 [1,01-1,02]; p = 0,044). No differences in recurrence were found among the patterns of LGE distribution (transmural/epicardial/subendocardial or peculiar segments localizations). The amount of BZ and the total amont of Core + BZ was related with VT recurrence (BZ 26,6 ± 13,9 vs 19,56 ± 9,69 g, HR 1,03 [1,01-1,06], p = 0,012; total Core + BZ 37,1 ± 18,2 vs 29,0 ± 16,3 g, HR 1,02 [1,00-1,04], p = 0,033). Finally VT recurrence was higher in patients with channels with transmural path (66,7% vs 31,4%, HR 3,25 [1,70-6,23], p &amp;lt; 0,001) or midmural channels (54,3% vs 27,6%, HR 2,49 [1,21–5,13], p = 0,013). CMR-aided scar dechanneling is a helpful and feasible technique which could identify patients with high risk of VT recurrence. High left ventricular mass, septal LGE distribution, transmural and midmural heterogeneous tissue channels were predictive factors of post ablation VT recurrence. Abstract Figure. VTchannel &amp; heterogeoneus tissue channel

Incidence of Germline ATM Variants in a Consecutive Clinical Cohort of CLL Patients

Incidence of Germline ATM Variants in a Consecutive Clinical Cohort of CLL Patients

2395LGE CMR predicts sudden death and VT in adults with repaired tetralogy of Fallot - a prospective study with 3500 patient follow up years

Abstract Background Adults with repaired tetralogy of Fallot (rtoF) are at risk of ventricular arrhythmia and sudden cardiac death (SCD). Cross-sectional data suggest association of late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) with adverse clinical risk factors Purpose We sought to determine prognosis related to LGE CMR. Methods In this prospective cohort study the primary composite outcome comprised the first of cardiovascular death (SCD or heart failure-related), aborted SCD (successfully resuscitated cardiac arrest or appropriate AICD shock for ventricular fibrillation), and clinical sustained ventricular tachycardia (VT&gt;30 seconds duration). Results In 531 rtoF patients (median age 32; 23–42, 296 (56%) male, NYHA≥II 17%) followed up after LGE CMR for median 5 (1.7–8.9) years, there were 39 primary composite outcomes: 10 SCD, 11 heart failure related deaths (2 perioperative RV failure), 2 aborted SCD and 16 clinical sustained VT events. At study end, there were 28 ventricular arrhythmic events in 28 rtoF patients (10 SCD, 16 clinical sustained VT, 2 aborted VF) that were significantly predicted by RV LGE extent (HR 1.45 CI: 1.3–1.6; P&lt;0.001). Univariable predictors of the primary outcome were RV LGE score; HR: 1.44 (1.31–1.57; p&lt;0.001), (Figure) together with older age; HR: 1.05 (1.02–1.07; P&lt;0.001), late repair; HR: 1.04 (1.02–1.07; p&lt;0.001), lower RV ejection fraction; HR: 0.92 (0.89–0.95; p&lt;0.001), larger RVOT akinetic length; HR: 1.04 (1.02–1.06; p&lt;0.001) larger right atrial area; HR: 1.2 (1.12–1.29; p&lt;0.001); higher BNP levels; HR: 1.01 (1–1.02; p&lt;0.001), lower peak VO2; HR: 0.89 (0.83–0.96; p=0.001), prior atrial arrhythmia; HR: 5.3 (2.8–10.07; p&lt;0.001), and non-sustained VT; HR: 4.1 (2.1–7.7; p&lt;0.001). Inducible VT did not predict the primary outcome; HR: 2.1 (0.57–8; p=0.25) In multivariable analysis both RV LGE score and indexed right atrial area (RAAi) only, remained predictive of the primary outcome (HR 1.29 CI: 1.12–1.49; p&lt;0.001 and HR 1.1 CI: 1.02–1.12; p=0.01, respectively). Patients could accordingly be stratified such that supramedian RV LGE score (≥5) and RAAi ≥16cm2/m2 had 5-year event free survival 84% vs 94% for supramedian RV LGE score (≥5) and RAAi &lt;16cm2/m2 or 98% for inframedian RV LGE score with RAAI&lt;16cm2/m2. Figure. Conclusions For every unit increase in CMR defined RV fibrosis score there is a 44% increased risk of sudden cardiac death and VT. LGE CMR and maximal right atrial area should therefore be incorporated into risk stratification for sudden death in adults with rTOF. Acknowledgement/Funding British heart foundation

Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters

BackgroundVenous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort. MethodsObservational, prospective study enrolling consecutive patients at a tertiary multi-disciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVC-related VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT. ResultsOverall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5–36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVC-related VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive. ConclusionsPaediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass. Clinical trial registrationACTRN12615000442505.

Abstract 16679: Plasma Omega-6 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome

Introduction: Prior studies have shown an inverse correlation between plasma omega-6 fatty acids (Ω6-PUFA) content and the risk of CV events in primary prevention populations. The prognostic value of Ω6-PUFA in patients after an acute coronary syndrome (ACS) is less clear. Methods: Baseline plasma Ω6-PUFA (7 species) was assessed through thin liquid chromatography in a case-control population (203 CV deaths, 271 VT, 325 MI, 161 AF and 1,612 controls) from MERLIN-TIMI 36, a randomized trial of ranolazine versus placebo in patients hospitalized with ACS. Logistic regression models were adjusted for age and sex, and then BMI, hypertension, prior MI, prior HF, diabetes mellitus, smoking, eGFR, LDL, HDL, TG, statin use, index diagnosis and treatment arm. Results: After age and sex adjustment, higher plasma gamma-linoleic acid (GLA) content was associated with a 22% lower odds of CV death (OR adj 0.78 per 1-SD, 95% CI 0.67-0.91). After further multivariable adjustment, higher plasma GLA remained significantly associated with lower odds of CV death (OR adj 0.84 per 1-SD, 0.71-0.99) [Figure] . Patients with higher plasma GLA content had significantly lower odds of AF (OR adj per 1-SD 0.79, 0.66 -0.94) and tended to have lower risk of VT (OR adj per 1-SD 0.90, 0.78-1.03; OR adj top quartile versus lowest quartile: 0.67, 0.45-1.00). GLA was not significantly associated with the risk of MI (OR adj 0.95, 0.83-1.08). Other Ω6-PUFA, including linoleic acid, were not consistently associated with CV events. Conclusions: Plasma gamma-linoleic acid content is significantly associated with the odds of CV death after ACS. Future research should examine whether dietary intake of GLA after ACS may help to attenuate CV risk.

Variability of Tidal Volume in Patient-Triggered Mechanical Ventilation in ARDS

Limiting tidal volume (VT) in patients with ARDS may not be achieved once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous patient-triggered modes that work differently across brands. We systematically investigated, using a bench model, the effect of patient-triggered modes on the size and variability of VT at different breathing frequencies (f), patient effort, and ARDS severity. We used a V500 Infinity ICU ventilator connected to an ASL 5000 lung model whose compliance was mimicking mild, moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling into 3 categories, namely volume control ventilation with mandatory minute ventilation; pressure control ventilation, including airway pressure release ventilation (APRV); and pressure support ventilation. Two levels of f and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) VT was compared across modes using non-parametric tests. The probability of VT > 6 mL/kg ideal body weight was assessed by binomial regression and expressed as the odds ratio (OR) with 95% CI. VT variability was measured from the coefficient of variation. VT distribution over all f, effort, and ARDS categories significantly differed across modes (P < .001, Kruskal-Wallis test). VT was significantly greater with pressure support (OR 420 mL, 95% CI 332-527 mL) than with any other mode except for variable pressure support level. Risk for VT to be > 6 mL/kg was significantly increased with spontaneous breaths patient-triggered by pressure support (OR 19.36, 95% CI 12.37-30.65) and significantly reduced in APRV (OR 0.44, 95% CI 0.26-0.72) and pressure support with guaranteed volume mode. The risk increased with increasing effort and decreasing f. Coefficient of variation of VT was greater for low f and volume control-mandatory minute ventilation and pressure control modes. APRV had the greatest within-mode variability. Risk of VT > 6 mL/kg was significantly reduced in APRV and pressure support with guaranteed volume mode. APRV had the highest variability. Pressure support with guaranteed volume could be tested in patients with ARDS.

Abstract 258: Pulmonary Overexpression of SERCA2A Improves Electrical Dysfunction and Suppresses Arrhythmias in Monocrotaline-induced Right Ventricular Failure

Background: Pulmonary Arterial Hypertension (PAH) is a major cause of mortality due, in large part to right ventricular (RV) failure. Its electrophysiological (EP) effects however are poorly defined. Recently, a gene therapy approach targeting SERCA2a (S2A) to the lungs improved RV mechanical function in a rodent PAH model. Whether this approach improves myocardial EP properties remains unknown. Methods: Male Sprague Dawley rats received a subcutaneous injection of monocrotaline (MCT 60mg/kg) leading to PAH induced RV failure. Three wks later, rats underwent intratracheal delivery of aerosolized AAV1.S2A (1E11 gc, N=6) or no treatment (MCT, N=7). Age matched rats served as controls (CTRL, N=5). The EP substrate and risk of VT were assessed using high resolution optical action potential (AP) mapping in ex vivo perfused hearts. Results: MCT (6/7) but not CTRL (0/5) hearts were prone to pacing-induced VT (P&lt;0.01). S2A gene therapy markedly suppressed the incidence of VT to &lt;15% (P&lt;.05 vs MCT). Investigation of the EP substrate revealed complete reversal of slow myocardial conduction in S2A treated compared to untreated MCT rats (Fig A, B) . AP duration (APD) and heterogeneity were increased in MCT and partially reversed by AAV1.S2A. Underlying the rise in heterogeneity was selective APD prolongation on the RV side causing &gt;90 degree clockwise shift in the orientation of the transepicardial gradient, an effect which was not reversed by AAV1.S2A (Fig C arrows) . Conclusion: S2A gene therapy to the lungs ameliorates PAH induced EP remodeling and arrhythmia propensity. Our findings highlight for the first time the utility of a non-cardiac gene therapy approach for arrhythmia suppression.