Prolonged QRS Research Articles

SUMOylation of the cardiac sodium channel NaV1.5 modifies inward current and cardiac excitability

Decreased peak sodium current (INa) and increased late sodium current (INa,L), through the cardiac sodium channel NaV1.5 encoded by SCN5A, cause arrhythmias. Many NaV1.5 post-translational modifications have been reported. A recent report concluded that acute hypoxia increases INa,L by increasing a Small Ubiquitin-like MOdifier (SUMOylation) at K442-NaV1.5. To determine whether and by what mechanisms SUMOylation alters INa, INa,L and cardiac electrophysiology. SUMOylation of NaV1.5 was detected by immunoprecipitation and immunoblotting. INa was measured by patch clamp with/without SUMO1 overexpression in HEK293 cells expressing wild type (WT) or K442R-NaV1.5 and in neonatal rat cardiac myocytes (NRCMs). SUMOylation effects were studied in vivo by electrocardiograms and ambulatory telemetry using Scn5a heterozygous knockout (SCN5A+/-) mice and the de-SUMOylating protein SENP2 (AAV9-SENP2), AAV9-SUMO1, or the SUMOylation inhibitor anacardic acid. NaV1.5 trafficking was detected by immunofluorescence. NaV1.5 was SUMOylated in HEK293 cells, NRCMs and human heart tissue. HyperSUMOylation at NaV1.5-K442 increased INa in NRCMs and in HEK cells overexpressing WT but not K442R-Nav1.5. SUMOylation did not alter other channel properties including INa,L. AAV9-SENP2 or anacardic acid decreased INa, prolonged QRS duration, and produced heart block and arrhythmias in SCN5A+/- mice, while AAV9-SUMO1 increased INa and shortened QRS duration . SUMO1 overexpression enhanced membrane localization of NaV1.5. SUMOylation of K442-Nav1.5 increases peak INa without changing INa,L, at least in part by altering membrane abundance. Our findings do not support SUMOylation as a mechanism for changes in INa,L. Nav1.5 SUMOylation may modify arrhythmic risk in disease states and represents a potential target for pharmacological manipulation.

QRS Prolongation After Seizure in a Patient with Venlafaxine Overdose

QRS Prolongation After Seizure in a Patient with Venlafaxine Overdose

Self-expanding TAVI using the cusp overlap technique versus the traditional technique: electrocardiogram changes and 1-year cardiovascular outcomes

Introduction and objectivesTranscatheter aortic valve implantation (TAVI) using the cusp overlap technique (COT) has shown a lower pacemaker implantation rate at 30 days. The objective of this study was to compare electrocardiogram changes and clinical outcomes between COT and the traditional technique (TT) at 1 year of follow-up. MethodsObservational, retrospective, nonrandomized study of consecutive patients undergoing TAVI between January 2015 and January 2021. Patients were matched using a propensity score and the TT was compared with COT. The primary endpoints were electrocardiogram changes and a combined endpoint including pacemaker implantation, hospitalization, or cardiovascular death at 1 year. ResultsWe included 254 patients. After propensity score matching, 184 patients (92 per group) remained. There were no statistically significant differences in baseline characteristics. At 1 year, COT patients showed a significant reduction in new onset left bundle branch block (49% vs 27%, P=.002) and less P wave (13.1±21.0 msec vs 5.47±12.5 msec; P=.003) and QRS prolongation (29.77±27.0 msec vs 16.38±25.4 msec, P <.001). COT was associated with a significant reduction in the occurrence of the primary endpoint (SHR, 0.39 [IC95%, 0.21-0.76]; P=.005). ConclusionsAt 1 year of follow-up, COT reduced the incidence of new onset left bundle branch block and diminished QRS and P wave widening compared with the TT. COT was also associated with a statistically significant reduction in the occurrence of the combined primary cardiovascular endpoint.

Electromechanical Dyssynchrony Is Associated With Right Ventricular Remodeling and Dysfunction Independently of Pulmonary Regurgitation Late After Tetralogy of Fallot Repair

The aim of this study was to investigate the relationship among right ventricular (RV) dilatation, dysfunction, and electromechanical dyssynchrony (EMD) in patients with repaired tetralogy of Fallot (rTOF). Data from a prospective rTOF registry of subjects with moderate or greater pulmonary regurgitation (PR) and contemporary imaging were analyzed. Electrocardiograms and echocardiograms were analyzed for EMD (prolonged QRS duration [QRSd], echocardiographic septal flash, and mechanical delay) and mechanical dispersion. The relationship among these, RV measurements on cardiac magnetic resonance, exercise capacity, and incident arrhythmia or death was analyzed with adjustment for PR. In total, 271 patients with rTOF (42% women; median age, 32years; interquartile range [IQR], 23-34 years) were included. Patients had moderate to severe PR (median PR fraction, 38%; IQR, 30%-47%), moderate to severe RV enlargement (median RV end-diastolic volume index, 161 mL/m2; IQR, 138-186 mL/m2) and mild RV systolic dysfunction (median RV ejection fraction [RVEF], 44%; IQR, 38%-48%). Eleven patients (4%) experienced ventricular arrhythmia or death. Presence of EMD was associated with larger RV size (RV end-diastolic volume index and RV end-systolic volume index, P=.006 and P<.001, respectively) and lower RVEF (P<.001). A sharp inflection in the relation among QRSd, RV size, and RVEF was observed when QRSd exceeded 150msec (3.1% decrease in RVEF for every 20-msec increase in QRSd between 160 and 200msec). Similar inflection points were observed for the mechanical delay between the RV basal-lateral and midseptal segments. The mechanical delay was higher in patients with vs without incident atrial arrhythmia (371 vs 276msec, P=.014). In adults with rTOF, EMD is independently associated with larger RV size, lower RVEF, and incident atrial arrhythmias.

#5630 SCREENING AND DIAGNOSIS STRATEGY FOR FABRY DISEASE IN TAIWANESE PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Fabry disease (FD) is not uncommon in patients with chronic kidney disease (CKD) who are on dialysis or have stroke at a young age, left ventricular hypertrophy (LVH) or hypertrophic obstructive cardiomyopathy (HOCM). However, FD is easily overlooked by physicians due to the heterogeneity of clinical manifestations. Therefore, an expert consensus meeting was held to establish a screening algorithm for FD in patients with CKD. Method The first meeting was held in Taiwan in August 2022. The screening criteria for FD with respect to age, sex, family history, cardiac involvement and signs and symptoms were discussed. The findings of meeting and the consensus opinion of the expert group were summarized. Results The screening algorithm was shown in Figure 1. It is recommended to screen for FD regardless of age. Screening for FD is recommended for CKD patients with family history of FD, stroke at young age (&amp;lt;55 years) or typical signs and symptoms including angiokeratoma, hypohidrosis, neuropathic pain, heat/cold and exercise intolerance, hearing loss and cornea verticillata. If CKD patients have one of the cardiac symptoms including dyspnea, palpitation and chest pain, it is recommended to check the cardiac-related red flags including LVH and HOCM using echocardiogram, short PQ interval, atrioventricular block and prolonged QRS interval using electrocardiogram, and low native T1 and posterolateral late gadolinium enhancement using magnetic resonance imaging. If cardiac-related red flags are present, screening for FD is recommended. Screening can also be performed in patients with CKD who do not have any typical symptoms but have a high suspicion of FD. In males, screening can be performed by measuring α-galactosidase A enzyme activity. If the enzyme activity is reduced or absent, assessment of globotriaosylsphingosine (lyso-Gb3) levels in plasma and genetic analysis are recommended. In female, assessment of lyso-Gb3 levels in plasma and genetic analysis are recommended. Conclusion FD is an underrecognized and not so rare disease. Physicians should maintain a skeptical attitude in clinical practice in order to make diagnosis in time and help patients and their entire families avoid life-threatening diseases at a young age. There are still more issues to be addressed, including whether to inform patients of the screening results, how to interact and communicate with patients, etc.

A Prospective Observational Study to Evaluate Cardiovascular Changes in Patients of Hypothyroidism.

Introduction Hypothyroidism is a common endocrine disorder in India and is easy to diagnose based on clinical manifestations and signs. Thyroid hormone affects the cardiovascular system. Fatiguability, dyspnea, weight gain, lower limb swelling, and bradycardia are some clinical manifestations. ECG changes in hypothyroidism include sinus bradycardia, prolonged QTc interval, changes in the morphology of the T-wave, QRS duration, and low voltage. Echocardiography changes include diastolic dysfunction, asymmetrical septal hypertrophy, and pericardial effusion. This study aimed to examine the cardiovascular changes in patients with hypothyroidism. Methodology Patients with hypothyroidism and cardiovascular changes were assessed using an electrocardiogram and echocardiography. Results A total of 68 hypothyroid patients were enrolled in the study. The mean age of patients was 41.93 ± 15.36 years, and the mean BMI was 24.64 ± 4.30 kg/m2. Of 68 hypothyroid patients, 57 (83.8%) were females, and 11 (16.2%) were males. The mean thyroid-stimulating hormone (TSH) level in the study population was 11.48 ± 22.02 (mIU/mL). The most common symptoms reported among the study participants were tiredness or weakness (67.6%), followed by dyspnea (42.6%). The mean pulse rate, systolic blood pressure, and diastolic blood pressure were 81.50 ± 16.16, 112.76 ± 7.05, and 70.68 ± 7.46, respectively. Pallor was the most common sign (22.1%) among all the people who participated in the study. The most common findings on the ECG were low voltage complexes (25%) followed by inversion of the T wave (23.5%). Other ECG findings were bradycardia (10.3%), right bundle branch block (7.4%), and QRS prolongation (2.9%). Echocardiography revealed 21 (30.8%) patients with grade 1 left ventricular diastolic dysfunction and pericardial effusion in two patients (2.94%). There was a significantly greater increase in the level of TSH in study participants. Conclusion Patients with abnormal ECG and echocardiography without other cardiovascular changes should be evaluated for hypothyroidism to improve the quality of care.

Value of frontal QRS axis for risk stratification of individuals with prolonged PR interval.

There is ongoing controversy regarding the prognostic value of PR prolongation among individuals free of cardiovascular diseases. It is necessary to risk-stratify this population according to other electrocardiographic parameters. This study is based on the Third National Health and Nutrition Examination Survey. Cox proportional hazard models were constructed and Kaplan-Meier method was used. A total of 6188 participants (58.1 ± 13.1 years; 55% women) were included. The median frontal QRS axis of the entire study population was 37° (IQR: 11-60°). PR prolongation was present in 7.6% of the participants, of whom 61.2% had QRS axis ≤37°. In a multivariable-adjusted model, mortality risk was highest in the group with concomitant prolonged PR interval and QRS axis ≤37° (hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.04-1.39). In models with similar adjustment where population were reclassified depending on PR prolongation and QRS axis, prolonged PR interval and QRS axis ≤37° was still associated with increased risk of mortality (HR: 1.18; 95% CI: 1.03-1.36) compared with normal PR interval. QRS axis is an important factor for risk stratification in population with PR prolongation. The extent to which this population with PR prolongation and QRS axis ≤37° is at higher risk of death compared with the population without PR prolongation.

Sinus rate and QRS duration on lead V1 predict major events in Brugada syndrome

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ministère de la Santé Française Background Arrhythmic risk stratification remains a major challenge in asymptomatic Brugada patients. Many studies have evaluated risk stratification performance based on a single or a few ECG-derived parameters measured manually. We aimed to assess the predictive value of multi ECG parameters measured automatically in patients with Brugada syndrome. Materials and Methods We performed a prospective, multicenter cohort study including Brugada patients with at least one available type 1 ECG (either spontaneously or drug-induced) between January 2005 and November 2021. Paper ECG were first digitized and then automatically analyzed using the Glasgow and Bravo algorithms (included in the logiciel CalECG). Clinical data and Brugada related events at diagnosis and during follow-up were collected. Sudden cardiac death, aborted cardiac arrest and appropriate ICD therapy in the VF zone were considered as major events. The predictive value of clinical and ECG parameters for symptomatic status was assessed using uni- and multivariate Cox models. Results ECGs from 301 Brugada patients (77% male, mean age at diagnosis 43 years, follow-up 7±5.6 years) were analyzed. Brugada-related symptoms (cardiac syncope or major event) occurred in 23% of patients before diagnosis and 11% during follow-up (incidence: 1.57%/year). After multivariate Cox analysis, only 2 baseline ECG (without Ajmaline) parameters were significantly associated with major events: RR interval (HR=1.01 (95%CI [1-1.01]), p=0.002) and QRS duration in lead V1 (HR=1.04 (95%CI [1-1.07]), p=0.038). QRS prolongation in lead V1 &amp;gt;113 ms (AUROC 0.69 (95% CI [0.58-0.8])) was associated with a 3-fold increased risk of major event (HR =3.49 (95% CI [1.72-7.09]), p=0.001). Conclusion Many previously described ECG parameter were not associated with major event in Brugada patients after multi-parameter evaluation. Sinus rate and QRS duration on lead V1 were independent risk factor. These results need to be validated on an external cohort. The predictive value of ECG parameters in Brugada syndrome should be assessed using automated multiparametric quantification.

ECG characteristics associated with adverse outcomes in COVID-19, a tertiary centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Background COVID-19 is a systemic disease with dominantly respiratory symptoms, however numerous other presentations involving practically any organ system have been described. Older patients and those with other comorbidities are at higher risk for critical COVID, increased respiratory requirements and death. (1) Those with cardiovascular comorbidities seem to be at a particular risk of detrimental outcomes. (2) Purpose The aim of our research was to see if certain ECG characteristics at admission could be predictive of unfavourable events in severe and critical COVID-19 patients. Methods We analyzed patient data and available ECG records at admission for 1752 consecutively hospitalized patients with severe and critical COVID-19 at our institution from March 2020 to June 2021. ECG records were obtained from our institution's medical archives, while patient data and outcomes were analyzed through electronic medical records. We analyzed the available ECGs recorded at admission for rhythm abnormalities, heart rate, ST segment changes, presence and localisation of Q waves, interventricular conduction abnormalities, AV conduction, PR, QRS and QTc interval duration, P, QRS and T wave axis, QRS-T angle and Sokolow-Lyon hypertrophy criteria. We defined primary outcomes as mechanical ventilation requirement and intrahospital death. Results Our results show that patients who required mechanical ventilation were significantly (P&amp;lt;0.05) more likely to have atrial fibrillation at admission, be tachycardic, have ST depression, have prolonged PR and QTc intervals, as well as pathological T wave axis and QRS-T angle. In multivariate analysis atrial fibrillation (OR 1.55, CI 1.07-2.23), tachycardia (OR 1.45, CI 1.17-1.80), prolonged PR interval (OR 1.88, CI 1.12-3.15) were independently associated with increased need for mechanical ventilation. Intrahospital mortality was significantly (P&amp;lt;0.05) increased in patients who had atrial fibrillation, were tachycardic, had ST depression or elevation, right bundle branch block, left bundle branch block, prolonged PR interval and QRS duration, short and long QTc interval, pathological T wave axis and QRS-T angle. Following multivariate adjustment, atrial fibrillation (OR 2.30, CI 1.59-3.32), tachycardia (OR 1.30, CI 1.05-1.61), ST depression (OR 1.91, CI 1.34-2.72), prolonged PR interval (OR 2.55, CI 1.53-4.25), short QTc interval (OR 8.64, CI 0.95-78.57) and pathological T wave axis (OR 0.71, CI 0.47-1.07) and QRS-T angle (OR 1.85, 1.25-2.73) independently significantly increased mortality. Conclusion Specific ECG changes seen already at admission seem to be associated with the need for mechanical respiratory support and increased mortality in COVID-19 patients. This readily available and easily utilised method can potentially help in early identification of those at risk in order to monitor patients more carefully and potentially alter early treatment approach.

Altered cardiac repolarization associated with cellular electrophysiological remodeling following chronic testosterone undecanoate administration in a canine model

Abstract Funding Acknowledgements Type of funding sources: None. Background The influence of testosterone on ventricular ion channels is widely investigated. Despite the legally stipulated availability of different androgen anabolic steroids (AAS), these agents are very popular among young adults, however, the direct effects of supra-physiological testosterone level are still unclear. Supposedly, the chronic use of AASs may result in structural and functional remodeling of the heart. Purpose The aim of our study was to investigate the potential electrophysiological effects of chronic administration of testosterone-undecanoate in a canine model in in vivo and in vitro studies. Methods Eight male beagle dogs were randomized into control (’Cont’) and treated (’Tr’) groups (n = 4; n = 4). The latter group received 15 mg/kg of long-lasting testosterone-undecanoate intramuscular injections weekly for 3 months. Blood samples were taken for monitoring testosterone levels. To investigate the altered repolarization in conscious dogs electrocardiography studies were performed. Ventricular myocytes were enzymatically dissociated via retrograde perfusion. The transmembrane ionic currents were recorded using the whole-cell configuration of the patch-clamp technique and the action potential duration (APD) was measured by the perforated patch-clamp technique. Results Testosterone level was significantly higher in the ‘Tr’ group compared to the ‘Cont’ group (47.02 nm/L vs. 15.23 nm/L; p=0.0002). The chronic treatment did not affect the heart rate between the examined groups (93.7±23.5 vs.108.8±21.4 beats/min), however, it resulted in significantly shortened QT (226±49 vs. 244.9±26.6 ms; p&amp;lt;0.05) and QTc (26.06±2.5 vs. 29.6±3.01 ms, p&amp;lt;0.05) intervals. ECG recordings also presented prolonged PQ (112.1±15.5 vs. 61.65±12.7ms; p&amp;lt;0.05), QRS (72.37±15.4 vs. 61.65±12.7 ms; p&amp;lt;0.05), and Tp-Te (32.95±7.45 vs. 53.46±16.6 ms; p&amp;lt;0.05) intervals in the ‘Tr’ group. Additionally, the APD of isolated left ventricular myocytes significantly shortened in the ‘Tr’ group compared to the ‘Con’ group (235.2±26.7 vs. 283.6±28.5 ms; p&amp;lt;0.05). Patch-clamp experiments revealed increased magnitude of transient outward potassium current (Ito), the inward rectifier potassium current (Ik1), and the slowed delayed rectifier potassium current (Iks) in the ‘Tr’ group. Conclusion The repolarization of the canine ventricular myocardium was significantly modified by constantly high level of testosterone. Many beneficial effects are attributed to physiological testosterone levels; however, the supra-physiological testosterone level may lead to potentially harmful alternations in the cardiac repolarization that may promote arrhythmogenesis, especially in the presence of various heart diseases. Presumably, the constantly high testosterone level induced electrophysiological changes may contribute to the development of life-threatening arrhythmias under certain circumstances.

Isolated PR prolongation in patients undergoing transcatheter aortic valve implantation

Abstract Funding Acknowledgements Type of funding sources: None. Background New conduction disturbances are common complications following transcatheter aortic valve implantation (TAVI). The last ESC guidelines recommended electrophysiological study (EPS) or long-term monitoring for patients with new LBBB above 150 ms or one that is associated with PR prolongation (IIa indication). For patients with preexisting conduction abnormality and further PR or QRS prolongation EPS or long-term monitoring are also recommended but with a IIb recommendation. The data regarding the prognosis and management of patients with isolated PR prolongation is limited. Purpose Evaluate the need for permanant pacmaker implantation, occurance of syncope and mortality during the 1st year following Transcatheter aortic valve implantation Methods All patients undergoing TAVI at Shaare Zedek Medical Center were retrospectively reviewed. All patients underwent at least 1 ECG prior and daily post the procedure. Patients with isolated PR prolongation &amp;gt; 20 ms compared to baseline ECG were included. While patients with preexisting permanent pacemaker (PPM), complete AV block or any peri or post procedural QRS widening &amp;gt; 20 ms were excluded. Patient were followed for 1 year for the occurrence of syncope, PPM or death. Results Excluding patients with preprocedural PPM, 1028 patients were reviewed. Compared to baseline ECG, 124 (12%) patients had isolated PR prolongation, of whom 88 (71%) and 36 (29%) had baseline narrow and wide QRS respectively. During follow-up none of these 88 patients with baseline narrow QRS required in hospital PPM, while only 2 patients with baseline wide QRS required in hospital PPM. During 1 year follow-up, 6 patients (4.8%) died and no one had syncopal episode or need for PPM. Conclusion Post TAVI, isolated new PR prolongation is not associated with an adverse outcome including syncope or progression to complete heart block and need for PPM at 1 year post the procedure. These finding may be considered when evaluating these patients post the procedure.

Detecting hypoglycemia-induced electrocardiogram changes in a rodent model of type 1 diabetes using shape-based clustering.

Sudden death related to hypoglycemia is thought to be due to cardiac arrhythmias. A clearer understanding of the cardiac changes associated with hypoglycemia is needed to reduce mortality. The objective of this work was to identify distinct patterns of electrocardiogram heartbeat changes that correlated with glycemic level, diabetes status, and mortality using a rodent model. Electrocardiogram and glucose measurements were collected from 54 diabetic and 37 non-diabetic rats undergoing insulin-induced hypoglycemic clamps. Shape-based unsupervised clustering was performed to identify distinct clusters of electrocardiogram heartbeats, and clustering performance was assessed using internal evaluation metrics. Clusters were evaluated by experimental conditions of diabetes status, glycemic level, and death status. Overall, shape-based unsupervised clustering identified 10 clusters of ECG heartbeats across multiple internal evaluation metrics. Several clusters demonstrating normal ECG morphology were specific to hypoglycemia conditions (Clusters 3, 5, and 8), non-diabetic rats (Cluster 4), or were generalized among all experimental conditions (Cluster 1). In contrast, clusters demonstrating QT prolongation alone or a combination of QT, PR, and QRS prolongation were specific to severe hypoglycemia experimental conditions and were stratified heartbeats by non-diabetic (Clusters 2 and 6) or diabetic status (Clusters 9 and 10). One cluster demonstrated an arrthymogenic waveform with premature ventricular contractions and was specific to heartbeats from severe hypoglycemia conditions (Cluster 7). Overall, this study provides the first data-driven characterization of ECG heartbeats in a rodent model of diabetes during hypoglycemia.

Cardiac resynchronization therapy induced QRS narrowing: could it change the prognosis?

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) responders should have symptomatic improvement and benefits in long-term outcomes. CRT is indicated in the treatment of heart failure (HF) patients with systolic dysfunction and prolonged QRS duration. There are conflicting results regarding QRS narrowing on CRT response. Objective We ought to access the impact of QRS narrowing after CRT implantation in clinical outcomes and arrhythmic events. The association between the QRS duration reduction in responders and non-responders was determined. Methods We retrospectively enrolled 110 consecutive patients with CRT. Native QRS duration and QRS duration at least 6 months after procedure were determined by EKG. Baseline clinical characteristics were accessed. Three outcomes were created. Primary outcome: hospitalization or emergency department admissions due to HF decompensation. Secondary outcome: sustained ventricular arrhythmic events. Tertiary MACE outcome (composite of cardiovascular death, hospitalization due to HF or acute coronary syndrome and cerebrovascular events). Results Out of 110 patients included, the mean age was 70.3 ± 10.7 years, 68.2% were male and mean body mass index was 29.1 ± 5.7 kg/m2. Baseline characteristics were similar between genders: 41.1% had atrial fibrillation, 10.3% peripheral arterial disease, 72.9% hypertension, 66.4% dyslipidemia, 44.9% diabetes and 20.7% chronic kidney disease. Ischemic etiology (p 0.001), pulmonary lung obstructive disease (p &amp;lt;0.001; r=0.35) and smoking habits (p &amp;lt;0.001; r=0.5) prevailed in male patients. Responders by clinical and/or echocardiographic criteria were 62.7%. Native QRS mean duration was 162.4 ± 22 ms and mean QRSd after CRT was 141.9 ± 37 ms, with a median QRS narrowing of 20 ± 30 ms. Primary outcome occurred in 28.6%, secondary in 16.4% and MACE occurred in 31.8%. QRS narrowing was an independent predictor of primary and secondary outcomes (U 283; p 0.016 and U 110.5; p 0.043) as well as MACE (U 6.18; p 0.035). ROC curve analysis compared native and post-CRT implantation QRSd and their impact on outcomes. The best cut-off values for hospitalization and MACE were 10 and 13, respectively (AUC 0.69; 95% CI 0.54 – 0.84; p 0.016 and AUC 0.64, 95% CI 0.52 – 0.76; p 0.035). Conclusion Patients with a larger decrease in QRS duration after CRT implantation revealed improved outcomes and it was independent of CRT response. This variable could be of interest in selecting HF patients for CRT.

TAVI autoexpandible con superposición de senos coronarios frente a la técnica tradicional: alteraciones en el ECG y eventos cardiovasculares al año

Introduction and objectivesTranscatheter aortic valve implantation (TAVI) using the cusp overlap technique (COT) has shown a lower pacemaker implantation rate at 30 days. The objective of this study was to compare electrocardiogram changes and clinical outcomes between COT and the traditional technique (TT) at 1 year of follow-up. MethodsObservational, retrospective, nonrandomized study of consecutive patients undergoing TAVI between January 2015 and January 2021. Patients were matched using a propensity score and the TT was compared with COT. The primary endpoints were electrocardiogram changes and a combined endpoint including pacemaker implantation, hospitalization, or cardiovascular death at 1 year. ResultsWe included 254 patients. After propensity score matching, 184 patients (92 per group) remained. There were no statistically significant differences in baseline characteristics. At 1 year, COT patients showed a significant reduction in new onset left bundle branch block (49% vs 27%, P=.002) and less P wave (13.1±21.0 msec vs 5.47±12.5 msec; P=.003) and QRS prolongation (29.77±27.0 msec vs 16.38±25.4 msec, P <.001). COT was associated with a significant reduction in the occurrence of the primary endpoint (SHR, 0.39 [IC95%, 0.21-0.76]; P=.005). ConclusionsAt 1 year of follow-up, COT reduced the incidence of new onset left bundle branch block and diminished QRS and P wave widening compared with the TT. COT was also associated with a statistically significant reduction in the occurrence of the combined primary cardiovascular endpoint.

CI-452767-1 THE ASSOCIATION BETWEEN QRS NARROWING WITH CARDIAC RESYNCHRONIZATION THERAPY, MORTALITY AND HEART FAILURE: A POST-HOC ANALYSIS OF THE RESYNCHRONIZATION IN AMBULATORY HEART FAILURE TRIAL (RAFT)

Amongst patients with left ventricular systolic dysfunction and prolonged QRS, cardiac resynchronisation therapy (CRT) can improve cardiac electrical/mechanical synchrony, and prevent adverse clinical outcomes. The baseline QRS duration is associated with improved response to CRT. However, the association between QRS narrowing after implantation and clinical response to CRT is unclear. To determine whether the degree of QRS narrowing is associated with clinical outcome following CRT implantation. The RAFT study enrolled 1798 patients with left ventricular ejection fraction (LVEF) ≤35%, QRS duration ≥120 ms and NYHA II-III to CRT-D or ICD. 894 were randomized to CRT-D of which 821 patients received CRT-D and had electrocardiograms (ECGs) available for review. The degree of QRS narrowing (dQRS) was calculated as the difference between baseline QRS duration and the widest QRS with CRT pacing post implantation. The primary outcome was a composite of death and heart failure hospitalisation. Multivariable Cox proportional hazards models were performed to assess the association between dQRS and the incidence of the primary composite outcome. To model the variation in risk of the outcome by dQRS, a restricted cubic spline function was used. The median age was 67 (IQR 59-73) years, 125 patients (15.2%) were women, median LVEF 24%, 68% had ischemic heart disease and 30% had atrial fibrillation. The baseline median QRS duration was 160 (IQR 140-178.5) ms, 68% had a left bundle branch block (LBBB). The median dQRS was 2 ms (IQR -18-20 ms), and 450 (55%) of patients had QRS narrowing post CRT. dQRS was associated with a reduction in the composite outcome (HR = 0.988, 95% CI 0.984-0.993), all-cause mortality (HR = 0.990, 95% CI 0.984-0.995) and heart failure hospitalisation (HR 0.990, 95% CI 0.985-0.997) in patients with CRT, following adjustment for age, sex, non-ischaemic cardiomyopathy, LVEF, atrial fibrillation/flutter, NHYA class, and peripheral vascular disease (Figure 1A). Similar findings were seen in the group without LBBB at baseline (HR 0.992, 95% CI 0.985-0.999) (Figure 1B). Amongst patients receiving CRT for left ventricular systolic dysfunction with QRS prolongation, any degree of QRS narrowing was found to be associated with an increasing reduction in mortality and heart failure, irrespective of the QRS morphology at baseline. This finding may improve outcomes in patients undergoing CRT implantation, particularly in those with a non-LBBB QRS morphology.

Sinus rate and QRS duration on lead V1 predict major events in Brugada syndrome

Arrhythmic risk stratification remains a major challenge in asymptomatic Brugada patients. Many studies have evaluated risk stratification performance based on a single or a few ECG-derived parameters measured manually. We aimed to assess the predictive value of multi ECG parameters measured automatically in patients with Brugada syndrome. We performed a prospective, multicenter cohort study including Brugada patients with at least one available type 1 ECG (either spontaneously or drug-induced) between January 2005 and November 2021. Paper ECG were first digitized and then automatically analyzed using the Glasgow and Bravo algorithms. Clinical data and Brugada related events at diagnosis and during follow-up were collected. Sudden cardiac death, aborted cardiac arrest and appropriate ICD therapy in the VF zone were considered as major events. The predictive value of clinical and ECG parameters for symptomatic status was assessed using uni- and multivariate Cox models. ECGs from 301 Brugada patients (77% male, mean age at diagnosis 43 years, follow-up 7 ± 5.6 years) were analyzed. Brugada-related symptoms (cardiac syncope or major event) occurred in 23% of patients before diagnosis and 11% during follow-up (incidence: 1.57%/year). After multivariate Cox analysis, only 2 baseline ECG (without Ajmaline) parameters were significantly associated with major events: RR interval (HR = 1.01 [95%CI 1–1.01], P = 0.002) and QRS duration in lead V1 (HR = 1.04 [95%CI 1–1.07], P = 0.038). QRS prolongation in lead V1 > 113 ms (AUROC 0.69 [95%CI 0.58–0.8], Fig. 1) was associated with a 3-fold increased risk of major event [Fig. 2] (HR = 3.49 (95% CI [1.72–7.09], P = 0.001). Many previously described ECG parameter were not associated with major event in Brugada patients after multi-parameter evaluation. Sinus rate and QRS duration on lead V1 were independent risk factor. These results need to be validated on an external cohort. The predictive value of ECG parameters in Brugada syndrome should be assessed using automated multiparametric quantification.

Cardiac Inflammation As an Underlying Trigger for the Pathological Deficits Associated with Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disorder that causes cardiomyocyte loss, resulting in myocardial fibro-fatty deposition leading to cardiac dysfunction and sudden cardiac death, particularly in young patients and athletes, with no available treatments. The genetics of ARVC follow an autosomal dominant pattern, although severe cases (especially in pediatric populations) have been reported as recessive. Mutations in genes encoding components of desmosomes (specialized cell-cell junction that act as mechanical anchor between cardiac muscle cells) resulting in loss of desmosomal proteins underlie approximately 40-60% genetic cases of ARVC. Studies highlight that cardiac inflammation may be a critical and early component of ARVC as patients harboring mutations in the desmosomal gene desmoplakin (DSP) present with recurrent myocardial episodes (observed as myocarditis); however, the mechanisms and whether inflammation is a driver of ARVC remain unclear. We hypothesize that desmosomal gene mutations/loss/byproducts alter the acute inflammatory response on the cardiomyocyte cell surface leading to chronic immune intolerance and triggering of ARVC disease. To test our hypothesis, we injected DSP heterozygous deficient mice (harboring 50% loss of DSP without overt signs of ARVC) with a fragment of α-myosin and pertussis toxin to stimulate the immune system to assess its impact on ARVC pathogenesis. We show that DSP heterozygous mice exposed to acute immunological challenge triggered a destructive cardiomyocyte immune response in DSP heterozygous deficient hearts, reminiscent of fulminant myocarditis. Furthermore, we show that this acute immunological challenge was sufficient to trigger classic ARVC disease features in DSP heterozygous deficient mice as exemplified by: (i) enlarged ventricular (mostly right ventricular) chambers and heart size, (ii) fibrotic remodeling, with more clearly striking effects in the right ventricle (RV), (iii) epicardial fat tissue accumulation, (iv) electrophysiological deficits, such as premature ventricular contractions and QRS prolongation as well as (v) right and left ventricular physiological deficits associated with the bi-ventricular form of ARVC, although the RV appeared to be more significantly impacted. Our studies highlight the development of a novel DSP-related model of myocarditis. Using this model, we show that immunological stress is sufficient to lead to loss of cardiomyocyte immune tolerance in DSP heterozygous deficient mice with compromised desmosomal integrity to drive ARVC pathogenesis. More broadly these studies suggest that the immune system maybe an important driver of ARVC pathogenesis in patients with underlying desmosomal gene mutations/heterozygous loss, especially in the setting of autosomal dominant genetics. Work in the laboratory of FS is supported by grants from the NIH (HL142251, HL162369) and industry (LEXEO Therapeutics Inc.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

PO-05-038 CONDUCTION SYSTEM CONCERNS DURING PVC ABLATION AT THE POSTERIOR SUPERIOR PROCESS OF THE LEFT VENTRICLE: A SAFE APPROACH FROM ALL ANGLES

Ventricular arrhythmias (VA) originating from the posterior superior process (PSP) are infrequent and challenging to treat with catheter ablation due to their location in the highest portion of the inferior left ventricular (LV) septum , proximity to the conduction system and origin between LV and right atrium. The incidence of conduction system abnormality from ablation in this area is ill-defined. To describe procedural approach and outcome of PSP ablation including conduction system effect. We reviewed our institutional VA ablation database between 1/2019-11/2022 to identify patients (pts) who underwent PSP ablation. Incidence, procedural technique, and outcomes (including conduction abnormalities and procedural success) are evaluated. Among 556 pts who underwent VA ablation during this period, nine patients (1.6%) underwent PSP ablation. Sustained VT was present in 1 and the remainder had ablation for PVCs. Three patients (33%) were female, 3 pts had prior VA ablation. Mean LVEF was 50.6% +/-7 %, and two patients had structural heart disease with scar on cardiac MRI. The VA morphology had some variance but shared common characteristics including leftward axis, rs in II, negative (QS or rS) in III, and predominantly positive concordance in precordial leads, similar to previously reported series (Figure 1). During ablation, five pts (55.5%) had fast junctional rhythm, and one (11.1%) had transient complete heart block. No one had HV or QRS prolongation post procedure. Two (22.2%) patients had >30 msec AH prolongation, and four (44.4%) patients had >30 msec PR prolongation. Ablation from the right atrium (RA) in 2, coronary sinus (CS) in 3, and from the left ventricular (LV) septum in 8 patients. The patient who had transient complete heart block had full recovery and did not require pacemaker (PPM) implant, and one patient with post procedure AH and PR prolongation required PPM ten months after the procedure. During mean follow-up of 13.8 +/- 10.5 months, 83.3% patients had <3% PVC burden, and there were 92% absolute reduction in PVC burden (P<0.05). Ablation for VA originating from the PSP is associated with a risk of damage to the upper AV conduction, predominantly manifesting as AH prolongation. Care should be taken to monitor conduction during ablation to avoid permanent damage to the conduction system. Despite this, successful ablation can be achieved from the RA, CS or the LV septum.Tabled 1Table 1VA ablation at PSPN=9Age66.4 +/- 16.4Female3 (33%)LVEF (%)50.6 +/-7 %Prior VA ablation0.78 +/- 1.5Abnormal imaging with scar2 (22%)Conduction system disturbance during procedureFast junctional rhythm during ablation5 (55.5%)Transient heart block during ablation1 (11.1%)AH prolongation > 30msec post procedure2 (22.2%)HV prolongation > 30msec post procedure0PR prolongation > 30msec post procedure4 (44.4%)QRS prolongation > 10msec post procedure0Procedure detailAblation form the RA2 (22.2%)Ablation from the CS3 (33.3%)Ablation from the LV8 (88.8%)Ablation with RF energy9 (100%)Ablation with cryo energy0Procedure outcomeMean follow up (months)13.8 +/- 10.5Pre procedure PVC burden (%) *14.8+/- 11.5Post procedure PVC burden (%) **1.32 +/- 1.9VT recurrence ***0Required pacemaker implant1 (11.1%)* Seven patients had information on pre-procedure PVC burden. ** Six patients had information on post-procedure PVC burden. *** One patient had VT ablation. VA: Ventricular arrhythmia, PSP: posterior superior process, LVEF: left ventricular ejection fraction, RA: right atrium, CS: coronary sinus, LV: left ventricle, RF: radiofrequency. Open table in a new tab

PO-01-179 MOVING BEYOND QRS DURATION: QRS VOLTAGE-TIME-INTEGRAL (AREA) IS A SUPERIOR PREDICTOR OF CLINICAL RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY

Cardiac resynchronization therapy (CRT) can alleviate left ventricular (LV) electrical dyssynchrony mediated systolic heart failure (HF). Prolonged baseline QRS duration (QRSd) is the only conventional quantitative ECG criteria to assess left ventricular electrical dyssynchrony. Evaluate the baseline QRS voltage-time-integral (VTI), along with QRSd, and their reduction effect after CRT as predictors of future HF events. We included 595 patients (68.1±11.5 yr., 32.6% women, 43.9% ischemic cardiomyopathy, baseline LV ejection fraction 25.8±8.3%) who underwent CRT-defibrillator implant for clinical indications 2012-2019 and analyzed their ECGs before and after CRT. Orthogonal X, Y, Z leads were reconstructed from 12-lead ECG using Kors’s matrix. VTIQRS-X, Y ,Z and VTIQRS-3D were obtained from integration over the duration of QRS in X, Y, Z and root-mean-squared (3D) ECGs respectively. Follow-up clinical data including heart failure hospitalization, death, LV assist device (LVAD) implant, and orthotopic heart transplantation (OHT) were obtained from retrospective chart review. We used proportional hazard models to evaluate ECG variables as predictors of time to (a) composite death/LVAD/OHT and (b) first HF hospitalization over follow-up of 48.7±26.2 months. Models were adjusted for confounding by age, sex, ischemic cardiomyopathy and LV ejection fraction. QRSd reduced from 153±26 to 137±22 ms with CRT but neither baseline QRSd nor Δ QRSd predicted clinical outcomes. VTIQRS-3D and VTIQRS-Z of 104±49 and 75±44 respectively improved to 67±34 and 33±24 μVs. Significant unadjusted predictors of death/LVAD/OHT included VTIQRS-3D (p=0.047) and VTIQRS-Z (p=0.002) at baseline, and Δ VTIQRS-Z (p=0.01). On multivariable adjustment, VTIQRS-Z (p=0.005) and Δ VTIQRS-Z (p=0.02) remained significant. Δ VTIQRS-Z was the only significant predictor of HF hospitalizations (unadjusted p=0.02 and adjusted p=0.047). In patients undergoing CRT, a larger baseline QRS VTI from Z (anteroposterior) axis ECG predicted reduced death/LVAD/OHT. Further, a larger reduction in Z axis QRS VTI was associated with reduced death/LVAD/OHT and HF hospitalizations. VTIQRS-Z should replace QRSd for CRT patient selection and prognostication.

PO-02-235 MOVING BEYOND QRS DURATION: QRS VOLTAGE-TIME-INTEGRAL (AREA) IS A SUPERIOR PREDICTOR OF CLINICAL RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY

Cardiac resynchronization therapy (CRT) can alleviate left ventricular (LV) electrical dyssynchrony mediated systolic heart failure (HF). 15% reduction in LV end systolic volume (LVESV) with CRT is a validated surrogate of improved clinical outcomes. Prolonged baseline QRS duration (QRSd) is the only conventional quantitative ECG criteria to assess left ventricular electrical dyssynchrony. In addition to QRS duration, we evaluated the baseline QRS voltage-time-integral (VTI) and its reduction after CRT as predictors of LV reverse remodeling. We included 595 patients (68.1±11.5 yr., 32.6% women, 43.9% ischemic cardiomyopathy) who underwent CRT-defibrillator implant for clinical indications 2012-2019 and analyzed their ECGs before and after CRT. Orthogonal X, Y, Z leads were reconstructed from 12-lead ECG using Kors’s matrix. VTIQRS-X, Y ,Z and VTIQRS-3D were obtained from integration over the duration of QRS in X, Y, Z, and root-mean-squared (3D) ECGs respectively. We reviewed echocardiogram reports to obtain LV measures before and 3-12 months after CRT, including ejection fraction (LVEF), internal dimensions in diastole (LVIDd) and systole (LVIDs), end-diastolic (LVEDV) and LVESV. We used linear regression models to evaluate ECG variables as predictors of change in LV measures. We further used unadjusted and multivariable-adjusted logistic regression models to predict ≥15% reduction in LVESV from ECG variables. Baseline LVEF was 25.8±8.3%, LVIDd 5.7±0.9 cm, LVIDs 4.8±0.9 cm, LVEDV 164±67 and LVESV 109±56 mL. QRSd reduced from 153±26 to 137±22 ms with CRT. VTIQRS-3D and VTIQRS-Z of 104±49 and 75±44 respectively improved to 67±34 and 33±24 μVs. Baseline and change in VTIQRS-Z and VTIQRS-3D were more significantly associated with change in echo variables as compared to baseline and change in QRSd (Table 1). ≥15% reduction in LVESV was independently predicted by baseline VTIQRS-Z ≥71 μVs (OR 2.0, 95% CI 1.3-3.0, p=0.0009) and Δ VTIQRS-Z ≥42 μVs (OR 2.1, 1.4-3.1, p=0.004). In patients undergoing CRT, baseline QRS VTI from Z (anteroposterior) axis ECG ≥71 μVs independently predicted 2 times higher odds of salutary reverse LV remodeling post CRT. Further, a reduction in VTIQRS-Z ≥42 μVs also predicted more than 2 times odds of revrse remodeling. VTIQRS-Z is a superior automatically calculable quantitative summary ECG marker for CRT patient selection and prognostication as compared to QRS duration.