| 1. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 2. |
- Skov, Morten W., et al.
(författare)
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Risk prediction of atrial fibrillation based on electrocardiographic interatrial block
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Background--The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. Methods and Results--Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. Conclusions--IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.
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| 3. |
- Axelsson, Jimmy, et al.
(författare)
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Ejection fraction in left bundle branch block is disproportionately reduced in relation to amount of myocardial scar
- 2018
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 51:6, s. 1071-1076
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The relationship between left ventricular (LV) ejection fraction (EF) and LV myocardial scar can identify potentially reversible causes of LV dysfunction. Left bundle branch block (LBBB) alters the electrical and mechanical activation of the LV. We hypothesized that the relationship between LVEF and scar extent is different in LBBB compared to controls. Methods: We compared the relationship between LVEF and scar burden between patients with LBBB and scar (n = 83), and patients with chronic ischemic heart disease and scar but no electrocardiographic conduction abnormality (controls, n = 90), who had undergone cardiovascular magnetic resonance (CMR) imaging at one of three centers. LVEF (%) was measured in CMR cine images. Scar burden was quantified by CMR late gadolinium enhancement (LGE) and expressed as % of LV mass (%LVM). Maximum possible LVEF (LVEFmax) was defined as the function describing the hypotenuse in the LVEF versus myocardial scar extent scatter plot. Dysfunction index was defined as LVEFmax derived from the control cohort minus the measured LVEF. Results: Compared to controls with scar, LBBB with scar had a lower LVEF (median [interquartile range] 27 [19–38] vs 36 [25–50] %, p < 0.001), smaller scar (4 [1–9] vs 11 [6–20] %LVM, p < 0.001), and greater dysfunction index (39 [30–52] vs 21 [12–35] % points, p < 0.001). Conclusions: Among LBBB patients referred for CMR, LVEF is disproportionately reduced in relation to the amount of scar. Dyssynchrony in LBBB may thus impair compensation for loss of contractile myocardium.
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| 4. |
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| 5. |
- Bacharova, Ljuba, et al.
(författare)
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ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy : The change of the paradigm
- 2023
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Ingår i: Annals of Noninvasive Electrocardiology. - 1082-720X. ; 29:1, s. e13097-
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Tidskriftsartikel (refereegranskat)abstract
- The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.
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| 6. |
- Bernikova, Olesya G., et al.
(författare)
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ECG Markers of Acute Melatonin Treatment in a Porcine Model of Acute Myocardial Ischemia
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:19
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Tidskriftsartikel (refereegranskat)abstract
- In myocardial ischemia, melatonin confers antiarrhythmic action, but its electrocardiographic expression is unclear. We aimed to evaluate the effects of melatonin treatment on electrocardiogram (ECG) parameters reflecting major arrhythmogenic factors and to test the association of these parameters with ventricular fibrillation (VF) incidence. Myocardial ischemia was induced by 40 min coronary artery occlusion in 25 anesthetized pigs. After induction of ischemia, 12 and 13 animals were given melatonin or placebo, respectively. Twelve-lead ECGs were recorded and durations of QRS, QT, Tpeak-Tend intervals and extrasystolic burden were measured at baseline and during occlusion. During ischemia, VF episodes clustered into early and delayed phases (<10 and >20 min, respectively), and QRS duration was associated with VF incidence. QT interval and extrasystolic burden did not differ between the groups. The Tpeak-Tend interval was progressively prolonged, and the prolongation was less pronounced in the treated animals. QRS duration increased, demonstrating two maxima (5–10 and 25 min, respectively). In the melatonin group, the earlier maximum was blunted, and VF development in this period was prevented. Thus, acute melatonin treatment prevented excessive prolongation of the QRS and Tpeak-Tend intervals in the porcine myocardial infarction model, and QRS duration can be used for the assessment of antiarrhythmic action of melatonin.
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| 7. |
- Bernikova, Olesya G., et al.
(författare)
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Prolonged repolarization in the early phase of ischemia is associated with ventricular fibrillation development in a porcine model
- 2023
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Repolarization prolongation can be the earliest electrophysiological change in ischemia, but its role in arrhythmogenesis is unclear. The aim of the present study was to evaluate the early ischemic action potential duration (APD) prolongation concerning its causes, expression in ECG and association with early ischemic ventricular fibrillation (phase 1A VF). Methods: Coronary occlusion was induced in 18 anesthetized pigs, and standard 12 lead ECG along with epicardial electrograms were recorded. Local activation time (AT), end of repolarization time (RT), and activation-repolarization interval (ARIc) were determined as dV/dt minimum during QRS-complex, dV/dt maximum during T-wave, and rate-corrected RT–AT differences, respectively. Patch-clamp studies were done in enzymatically isolated porcine cardiomyocytes. IK(ATP) activation and Ito1 inhibition were tested as possible causes of the APD change. Results: During the initial period of ischemia, a total of 11 pigs demonstrated maximal ARIc prolongation >10 ms at 1 and/or 2.5 min of occlusion (8 and 6 cases at 1 and 2.5 min, respectively) followed by typical ischemic ARIc shortening. The maximal ARIc across all leads was associated with VF development (OR 1.024 95% CI 1.003–1.046, p = 0.025) and maximal rate-corrected QT interval (QTc) (B 0.562 95% CI 0.346–0.775, p < 0.001) in logistic and linear regression analyses, respectively. Phase 1A VF incidence was associated with maximal QTc at the 2.5 min of occlusion in ROC curve analysis (AUC 0.867, p = 0.028) with optimal cut-off 456 ms (sensitivity 1.00, specificity 0.778). The pigs having maximal QTc at 2.5 min more and less than 450 ms significantly differed in phase 1A VF incidence in Kaplan-Meier analysis (log-rank p = 0.007). In the patch-clamp experiments, 4-aminopyridine did not produce any effects on the APD; however, pinacidil activated IK(ATP) and caused a biphasic change in the APD with initial prolongation and subsequent shortening. Conclusion: The transiently prolonged repolarization during the initial period of acute ischemia was expressed in the prolongation of the maximal QTc interval in the body surface ECG and was associated with phase 1A VF. IK(ATP) activation in the isolated cardiomyocytes reproduced the biphasic repolarization dynamics observed in vivo, which suggests the probable role of IK(ATP) in early ischemic arrhythmogenesis.
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| 8. |
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| 9. |
- Christiansen, Morten K, et al.
(författare)
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Incidence, Predictors, and Success of Ventricular Tachycardia Catheter Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (from the Nordic ARVC Registry).
- 2020
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 125:5, s. 803-811
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Tidskriftsartikel (refereegranskat)abstract
- Catheter ablation may reduce ventricular tachycardia (VT) burden in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, little is known about factors predicting need for ablation. Therefore, we sought to investigate predictors and use of VT ablation and to evaluate the postprocedural outcome in ARVC patients. We studied 435 patients from the Nordic ARVC registry including 220 probands with definite ARVC according to the 2010 task force criteria and 215 mutation-carrying relatives identified through cascade screening. Patients were followed until first-time VT ablation, death, heart transplantation, or January 1st 2018. Additionally, patients undergoing VT ablation were further followed from the time of ablation for recurrent ventricular arrhythmias. The cumulative use of VT ablation was 4% (95% confidence interval [CI] 3% to 6%) and 11% (95% CI 8% to 15%) after 1 and 10 years. All procedures were performed in probands in whom cumulative use was 8% (95% CI 5% to 12%) and 20% (95% CI 15% to 26%). In adjusted analyses among probands, only young age predicted ablation. In patients undergoing ablation, risk of recurrent arrhythmias was 59% (95% CI 44% to 71%) and 74% (95% CI 59% to 84%) 1 and 5 years after the procedure. Despite high recurrence rates, the burden of ventricular arrhythmias was reduced after ablation (p=0.0042). Young age, use of several antiarrhythmic drugs and inducibility to VT after ablation were associated with an unfavorable outcome. In conclusion, twenty percent of ARVC probands developed a clinical indication for VT ablation within 10 years whereas mutation-carrying relatives were without such need. Although the burden of ventricular arrhythmias decreased after ablation, risk of recurrence was substantial.
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| 10. |
- Gilljam, Thomas, et al.
(författare)
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Heart transplantation in arrhythmogenic right ventricular cardiomyopathy - Experience from the Nordic ARVC Registry
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 250, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There is a paucity of data on heart transplantation (HTx) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), and specific recommendations on indications for listing ARVC patients for HTx are lacking. In order to delineate features pertinent to HTx assessment, we explored the pre-HTx characteristics and clinical history in a cohort of ARVC patients who received heart transplants. Methods: Data from 31 ARVC/HTx patients enrolled in the Nordic ARVC Registry, transplanted between 1988 and 2014 at a median age of 46. years (14-65), were compared with data from 152 non-transplanted probands with Definite ARVC according to 2010 Task Force Criteria from the same registry. Results: The HTx patients were younger at presentation, median 31 vs. 38. years (p = 0.001). There was no difference in arrhythmia-related events. The indication for HTx was heart failure in 28 patients (90%) and ventricular arrhythmias in 3 patients (10%). During median follow-up of 4.9. years (0.04-28), there was one early death and two late deaths. Survival was 91% at 5. years after HTx. Age at first symptoms under 35. years independently predicted HTx in our cohort (OR = 7.59, 95% CI 2.69-21.39, p <. 0.001). Conclusion: HTx in patients with ARVC is performed predominantly due to heart failure. This suggests that current 2016 International Society for Heart and Lung Transplantation heart transplant listing recommendations for other cardiomyopathies could be applicable in many cases when taking into account the haemodynamic consequences of right ventricular failure in conjunction with ventricular arrhythmia.
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