Premature Ventricular Contraction Burden Research Articles

A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.

Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.

Predictors of improvement in LV ejection fraction post PVC ablation

Abstract Introduction Premature ventricular contraction (PVC) is a frequently encountered finding in routine ECGs, that in certain individuals may be followed by reduction in ejection fraction (EF). This may be improved or even reversed with a medical or interventional reduction of ectopic burden. Objective The primary objective of this study is to assess the potential effectiveness of cardiac ablation in suppressing PVC and subsequently enhancing the EF. Further we aim to establish predictive factors of the success of the intervention. Methods In a retrospective data analysis at a single medical centre, we examined records of 116 patients who underwent ectopic ablation, with 10 patients having more than 1 ablation. Demographic information, heart-related conditions along with the presence of a scar on MRI, was collected. The study also recorded pre- and post-procedure PVC burden and EF measurements. Results Demographics and procedural details are in table 1. It was found that patients participating in this study were predominantly male (66.4%), on average 60.1 (± 13.6) years old, overweight (BMI 29.8 ± 5.4) with no additional heart disease (56%) and no scarring on MRI (55%).The PVC burden before ablation (27.9 ± 12.7) significantly reduced to 8.0 ± 11.2 post-ablation (p &amp;lt; 0.005), marking an average relative reduction of 68.1% (± 44.1%). Successful interventions, defined by a reduction exceeding 50%, were observed in 79% of patients. The EF increased from 39.6 ± 8.9 to 47.5 ± 10.7 post-ablation (p &amp;lt; 0.005), corresponding to an average increase by 8.4 ± 8.5. Notably amongst the patients who had a successful ablation, 36% of patients achieved normalized EF (&amp;gt;55%) and 42% showed an improvement of at least 5%. A strong correlation emerged between the relative change in PVC and the ejection fraction measured after ablation, with an increase by 0.10 for every percent reduction (p &amp;lt; 0.00). The relative increase in the EF% was significantly higher in patients where the PVC burden was reduced by at least 50% (figure 1). Linear fixed effect modelling explored the influence of patient characteristics on the model. Patients with higher BMI had a lower EF after ablation with same relative reduction in PVC (p &amp;lt; 0.03). Similarly, a scar on MRI and associated heart condition was associated with reduced improvement in ejection fraction (p &amp;lt; 0.02). Also, for every increase in age patients had a reduction of 0.2 EF after ablation (p &amp;lt; 0.01). Right heart PVC’s were ablated more successfully, and had higher EF post ablation (p &amp;lt; 0.01). Conclusion In conclusion, reduction in PVC burden increases the EF after treatment. Increasing BMI, age and presence of associated heart disease can negatively impacted LVEF post ablation. Further research could improve the model that predicts improvement in LV function post successful PVC ablation.Figure 1Table 1

Premature ventricular contractions increase with heart rate in patients with mitral valve prolapse

Abstract Background A subset of patients with mitral valve prolapse (MVP) are at risk of life-threatening ventricular arrhythmias (VAs), and a high burden of premature ventricular contractions (PVCs) is associated with increased mortality in patients with MVP. Previous studies indicate that PVC burden could either increase with increasing heart rate (HR), decrease with increasing HR, or with no relationship to HR. The association between PVC burden and HR in MVP is not known, nor if there is an association with VAs. Purpose We aimed to explore the relationship between PVC burden and HR in patients with MVP. Furthermore, we aimed to explore whether the different PVC profiles were associated with severe VA. Methods In this cross-sectional ambispective outcome study, we included patients with MVP and available Holter monitorings with &amp;gt;100 PVCs per 24-hours seen at our tertiary centre. The Holter monitoring with the highest PVC burden was used in case of multiple recordings. We investigated the relationship between hourly PVC burden and hourly mean HR by univariable mixed linear regression. We defined PVC profiles as (1) fast-HR-dependent-PVC (F-HR-PVC) when there was a significant positive correlation, (2) slow-HR-dependent-PVC (S-HR-PVC) when there was a significant negative correlation, and (3) independent-HR-PVC (I-HR-PVC) when no correlation between PVC and HR was found. The significance was set to 0.05. Severe VA was defined as sustained ventricular tachycardia, non-sustained ventricular tachycardia with haemodynamic instability, ventricular fibrillation, aborted cardiac arrest, or appropriate shock by a primary preventive implantable cardioverterefibrillator. Severe VA was recorded from retrospective medical history, prospective ICD interrogation or monitoring with implantable loop recorder. Results We included 75 patients with &amp;gt;100 PVCs at Holter monitoring (median age 48 years [IQR 35-58], 58% female). The median PVC burden was 1.9% per 24-hours (IQR 0.4-7.2). We found F-HR-PVC in 49 patients (65%), S-HR-PVC in 1 (1%), and I-HR-PVC in 25 (33%). Twelve (16%) patients had severe VA and these had higher PVC burden compared to those without severe VA (7.3% per 24-hours [IQR 4.2-10.4] vs 1.1% per 24-hours [IQR 0.3-5.3], p=0.004). The median PVC burden was 1.5% (IQR 0.3-8.0) for F-HR-PVC, 5.7% for S-HR-PVC and 1.5% (IQR 0.3-8.0) for I-HR-PVC. We found no association between different PVC profiles and the presence of severe VA (F-HR-PVC 65% vs 67%, S-HR-PVC 2% vs 0%, I-HR-PVC 33% vs 33%, p&amp;gt;0.05 for all groups). Conclusion Fast-HR-dependent-PVC was most common in MVP patients, and slow-HR-dependent-PVC were rare. A higher PVC burden was associated with severe VA. However, different PVC profiles did not infer higher risk of severe VA in our study. Further studies are needed to explore whether distinct PVC profiles can predict severe VA in larger patient populations.

Cardiomyocyte-specific deletion of adhesion G protein-coupled receptor F5 (ADGRF5) increases susceptibility to stress and arrhythmia

G-Protein Coupled Receptors (GPCR) represent the largest family of cell surface receptors in the human body and serve as targets for more than 30% of all approved drugs. Adhesion GPCRs (AGPCR) are an understudied GPCR family containing numerous extracellular domains that interact with extracellular proteins, including many known mediators of cardiac remodeling responses to pathologic stress. However, their relative expression in the heart and impact on cardiac function normally or during disease has been largely unstudied. To address this, we evaluated RNASeq-attained AGPCR expression from left ventricular (LV) samples of adult mice, of which Adgrf5 was one of the most highly expressed. Notably, decreased ADGRF5 expression is observed across numerous failing human LV tissue GEO datasets, and C57BL6/J mice subjected to transaortic constriction (TAC) surgery to induce pressure overload-induced HF also displayed reduced LV Adgrf5 expression by 12 weeks post-TAC. Analysis of published single cell (sc)-RNASeq datasets confirmed Adgrf5 expression in cardiomyocytes (CM), which also decreased following TAC in mice and in CM from failing human hearts. To investigate the impact of CM-specific ADGRF5 on cardiac function and remodeling normally or during disease progression, we crossed floxed ADGRF5 (ADGRF5f/f) and αMHC-Cre mice to generate constitutive, CM-specific ADGRF5 knockout mice (F5cmKO). These mice display normal cardiac structure and function at 12 weeks of age versus αMHC-Cre mice, as assessed via echocardiography, gravimetrics and immunohistochemistry. However, F5cmKO mice develop cardiac dysfunction, maladaptive remodeling, and increased mortality over time, even in the absence of pathologic insult, suggesting a homeostatic function of CM-specific ADGRF5. Following TAC surgery, F5cmKO mice display similar outcomes including enhanced cardiac dysfunction with accelerated remodeling and increased mortality. To attain mechanistic insight into these outcomes, we performed RNA-sequencing on LV tissue of 12-week-old F5cmKO mice, identifying and subsequently validating Scn1b as significantly upregulated in F5cmKO CM. Scn1b encodes for the β subunits of voltage-gated sodium channels (Scnβ1/β1B), which regulate gating and kinetics of Nav1.5 as well as adhesive CM-CM interactions, disruption of which could lead to arrhythmias. Indeed, conscious electrocardiogram (ECG) readings via telemetry indicated F5cmKO mice had a high burden of premature ventricular contractions (PVC), including ventricular tachycardia associated with cardiac enlargement. Using a combination of luciferase and fluorescence resonance energy transfer (FRET) reporters and gene expression analyses in neonatal rat ventricular myocytes (NRVM), we confirmed that ADGRF5 controls Scn1b expression in a Gαq/11 protein-dependent manner. In all, we have discovered that loss of CM-specific ADGRF5 leads to increased Scn1b expression with enhanced susceptibility to stress, arrythmias and sudden death, thus may provide a novel GPCR target to promote the maintenance of cardiac rhythm. AHA Predoctoral Fellowship 834906 to J.M.E. P01 HL147841 to D.T. This is the full abstract presented at the American Physiology Summit 2024 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.

Effects of Premature Ventricular Complex Burden on Left Ventricular Global Longitudinal Strain in Patients without Structural Heart Disease.

Background: Evaluation of left ventricular (LV) function in patients with idiopathic premature ventricular contraction (PVC) with preserved LV ejection fraction (LVEF), especially in the subclinical stage, may be of great importance in terms of directing early treatment. Methods: A total of 122 patients, retrospectively recruited, were divided into three groups according to PVC burden: Group 1; 5% ≤ PVC < 10%, Group 2; 10% ≤ PVC < 15%, and Group 3; 15% ≤ PVC. Transthoracic echocardiography (TTE) was performed to evaluate LV parameters. Results: LV-GLS (Global longitudinal strain) was found to be significantly lower in groups 2 and 3 with high PVC burden (18.9% ± 1.4, 17.5% ± 2.1, 16.3% ± 1.3; p < 0.001, respectively). Correlation analysis revealed a positive and significant correlation between PVC burden and deterioration in LV-GLS (r: 0.536; p < 0.001). In addition, PVC burden was found to be an independent predictor of LV-GLS deterioration in multiple linear regression analysis (β: 0.525, p < 0.001). The ROC curve analysis demonstrated that a PVC burden cut-off value of 8.4% was associated with a LV-GLS deterioration greater than -18, with a specificity of 75.4% and a sensitivity of 75.4% (AUC: 0.81 [0.73-0.88] 95% CI; p < 0.001). Conclusions: PVC burden was an independent predictor of deterioration in LV-GLS. The presence of LV-GLS deterioration due to PVC burden emphasizes the necessity for closer patient monitoring, observation of the response to pharmacological treatment, and evaluation of early invasive treatment strategies in selected patient groups.

Clinical Characteristics and Features of Idiopathic Premature Ventricular Contractions with an Enlarged Left Atrium in Patients Without Structural Heart Diseases

Background and aims: Idiopathic premature ventricular contractions (PVCs) may cause subtle changes in left atrium (LA) structure and function. Here, we investigated whether serum sodium, body mass index (BMI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other characteristics might be associated with LA in these patients. Methods: A total of 268 consecutive patients diagnosed with idiopathic PVCs were retrospectively analyzed. We assessed associations of enlarged LA and with the clinical features obtained from 24-hour Holter monitoring, electrocardiography and serum data in patients with PVCs. Results: Patients with an enlarged LA (n = 101), compared with a normal LA (n = 167), had significantly lower serum sodium (140.9 ± 3.0 mmol/L vs 141.7 ± 2.8 mmol/L; P = 0.022), higher BMI (24.5 ± 2.7 kg/m2 vs 21.7 ± 2.5 kg/m2; P &lt; 0.001), higher NT-proBNP [99.3 (193.6) pg/mL vs 77.8 (68.8) pg/mL; P &lt; 0.001] and lower average heart rates (73.0 ± 8.0 bpm vs 75.3 ± 7.6 bpm; P = 0.019). No significant differences were observed in P-wave dispersion, QRS duration, PVC coupling interval, pleomorphism, circadian rhythm, non-sustained ventricular tachycardia, serum potassium, serum magnesium, hypersensitive C-reactive protein, low-density lipoprotein cholesterol, symptoms and PVC duration. Conclusions: Beyond the burden of PVCs, attributes such as serum sodium, BMI, NT-proBNP and average heart beats may potentially correlate with LA enlargement in individuals with idiopathic PVCs.

The role of heart rate variability in predicting the response to beta blocker in patients with frequent premature ventricular contractions

Abstract Background Frequent premature ventricular contractions (PVCs) in patients with structurally normal heart are not uncommon. Beta blocker is generally used to reduce symptom and burden of PVCs, but the response to beta blockers vary from patient to patient. Purpose This study aimed to investigate whether the heart rate variability (HRV) values could predict the response to beta blockers in patients with frequent PVCs. Methods We analyzed the patients who underwent 24-hour Holter monitoring and had PVC burden &amp;gt;3% in baseline 24-hour Holter monitoring. Bisoprolol and nebivolol was used to reduce symptom and burden of PVCs. The response to beta blocker was defined as the reduction of PVCs burden more than 50% in follow-up Holter monitoring. Baseline HRV was measured by time domain and frequency domain methods using 24-hour Holter monitoring. Results A total of 125 patients (mean age, 52.1 ± 14.7 years; male, 38.3%) underwent repeated 24-hour Holter monitoring were finally analyzed. Mean follow-up duration between the Holter monitoring was 205 ± 200 days. Among 125 patients with frequent PVCs, 45 patients had response to beta blockers. The ratio of low-frequency (LF) and high-frequency (HF) was higher in response group than those with non-response to beta blocker (P=0.016). LF, HF, and other variables measured by time-domain method were not associated with response to beta blocker. Conclusion The HRV value, especially LF/HF ratio, could predict the response to beta blockers in patients with idiopathic frequent PVCs.

Bilateral Cardiac Sympathetic Denervation for Refractory Multifocal Premature Ventricular Contractions in Patients With Nonischemic Cardiomyopathy

BackgroundBilateral cardiac sympathetic denervation (BCSD) for refractory life-threatening ventricular arrhythmias is a neuromodulatory intervention targeting sympathetically driven focal or re-entrant ventricular arrhythmias. ObjectivesThis study sought to provide a more complete and successful option for intervention in patients in whom premature ventricular contraction (PVC) ablation is not feasible or has been unsuccessful. MethodsA total of 43 patients with >5% PVC burden and concomitant nonischemic cardiomyopathy (NICM) who previously failed medical and ablation therapies were referred for BCSD. All patients underwent bilateral video-assisted thoracoscopic surgical approach with T1-T4 sympathectomy. Primary effectiveness endpoints were postprocedural PVC burden resolution, improvement in left ventricular ejection fraction (LVEF), and cessation of antiarrhythmic drugs (AADs). Safety endpoints included peri- and postprocedural complications. Outcomes were assessed over a 1-year follow-up period. ResultsAmong the 43 patients who underwent BCSD, the mean age was 52.3 ± 14.7 years, 69.8% of whom were male patients. Presenting mean LVEF was 38.7% ± 7.8%, and PVC burden was 23.7% ± 9.9%. There were significant reductions in PVC burden postprocedurally (1.3% ± 1.1% post-BCSD, compared with 23.7% ± 9.9% pre-BCSD, P < 0.001) and improvements in LVEF (46.3% ± 9.5% post-BCSD, compared with 38.7% ± 7.8% pre-BCSD, P < 0.001). The rate of ICD therapies decreased from 81.4% (n = 35) to 11.6% (n = 5) (P < 0.001), leading to a significant reduction in use of AADs (100.0% to 11.6%, P < 0.001) and improvement in mean NYHA functional class (2.5 ± 0.5 to 1.4 ± 0.2, P < 0.001). Major intraoperative complications were seen in 4.7% of patients (hemothorax and chylothorax). Of the patients, 81.4% (n = 35) experienced no mortality or major complications over a 1-year follow-up period, with the remaining still within their first year postprocedure. ConclusionsBCSD is effective for the management of refractory PVCs and ventricular tachycardia who have failed previous ablation therapy.

Abstract 14356: Higher Burdon of Premature Ventricular Complexes is Not Uncommon in Stable Well Treated Heart Failure Patients and Relate to Poorer Outcomes

Introduction: While premature ventricular contractions (PVCs) are generally considered benign, recent evidence suggests that even the contractions preceding PVCs are inefficient so that even a moderate burden of PVCs may be associated with loss of contractile efficiency and increased risk of events. It is however unclear what proportion of stable heart failure (HF) patients have a moderate to high burden of PVCs, despite being well-treated. Aim: The aim of this study was to assess the proportion of HF patients that have more than 5% PVCs and whether this higher number is related to worse outcomes. Methods: We retrospectively analyzed electronic medical records from 676 adult patients with either an ejection fraction &lt; 40% or NTproBNP more than 600 pg/ml at the Amsterdam UMC (AMC) who received Holter monitoring between 2014 and 2022. In a second independent cohort from a heart failure registry at Henry Ford Hospital (HFH) in Detroit, Michigan, we retrospectively reviewed all participants with ejection fraction &lt; 40% that had a Holter monitor at any point (n=180). Results: The median baseline age of the Amsterdam UMC patients was 62 and 40% were female. The HFH cohort had a median age of 64 years and 50% were female. Results are summarized in the table. During the follow-up period, significantly more patients died in the group with more than 5% PVCs (p &lt; 0.05 in the Amsterdam UMC cohort). Conclusions: We show in two independent cohorts that around 8-10% of HF patients have a significant burden of PVCs (i.e. &gt;5% of all heartbeats), despite adequate use of beta-blocker therapy. This proportion of PVCs is associated with an increased risk of death over one year. This suggests that in HFrEF patients, PVCs burden more than 5% of heartbeats may not be as harmless as often thought.

Abstract 18390: Ibrutinib Increases Ventricular Arrhythmia Burden Independently of Atrial Arrhythmia

Introduction: Use of Bruton Tyrosine Kinase inhibitors (BTKi) such as ibrutinib is frequently limited by atrial arrhythmia, possibly through off-target inhibition of C-Terminal-Src-Kinase (CSK). Whether BTKi can directly trigger ventricular arrhythmia is less clear. Case reports and retrospective analysis have suggested a link, but causal effect is not established. The association is further put into doubt by absent expression of CSK or BTK in ventricular cardiomyocytes, and absence of ventricular arrhythmia signals in meta-analyses of BTKi RCTs. Further study is critically needed. Hypothesis: Ibrutinib induces ventricular arrhythmia through a unique mechanism. Methods: We performed a retrospective crossover study of ibrutinib-treated patients with serial cardiac monitoring both on and off ibrutinib (pacemakers, loop recorders, or multiple holters) across a 10-year span in a large academic center to compare burden of atrial/ventricular ectopy on and off ibrutinib. A separate group of Chronic Lymphocytic Leukemia (CLL) patients with serial cardiac monitoring not on BTKi was used as additional controls. To determine biological correlation, we tested the ability of ibrutinib to induce arrhythmia in cultured human Induced Pluripotent Stem Cell derived ventricular cardiomyocytes (iPSC-vCMs). Results: 88% (15/17) of patients on ibrutinib with serial cardiac monitoring had increased burden of Premature Ventricular Contractions (PVCs), with an average increase of 155 PVCs/hour (p&lt;0.0001). An increase was not observed in the control cohort. Ventricular arrhythmia burden was not associated with atrial arrhythmia burden. Removing patient-related confounders, in vitro analysis of iPSC-vCMs demonstrated that ibrutinib induced arrhythmia following three days of treatment in a dose-dependent manner. Conclusions: In patients with continuous/serial cardiac monitoring, ibrutinib is associated with a significant increase in ventricular ectopy (average of 155 PVCs/hr). Lack of ventricular and atrial arrhythmia concordance suggests an alternative mechanism of arrhythmia induction. Increased arrhythmogenicity of human ventricular cardiomyocytes treated with ibrutinib indicates a direct myocardial mechanism.

Differential Profiles of Cortisol, Components of Autonomic Nervous System, and Self-Rated Health in Premature Ventricular Contraction: An Observational Study of Three Circadian Types

Objective: Premature ventricular contraction (PVC) exhibits one of the three circadian patterns, namely fast-type, slow-type, and independent-type. This study aimed to investigate whether the cortisol-marker of hypothalamic-pituitary-adrenal axis, autonomic nervous system activity, and perceptive self-rated health are associated with the three PVC circadian types.Methods: This cross-sectional observational study recruited 65 idiopathic PVC subjects (23 fast-, 20 slow-, and 22 independent-type) as well as 5 control subjects. Each subject underwent a 24- hour Holter to examine PVC burden and heart rate variability, collected saliva for cortisol and norepinephrine level measurement at 6–7 am, 10–11 am, and 10–11 pm, and recorded their self-rated health scales. Furthermore, univariate and multiple linear regression were conducted to investigate the associations between the independent variables and PVC burden.Results: The average PVC burden was 15.7%, 8.5%, and 13.6% in fast-, slow-, and independent-type idiopathic PVCs, respectively. Multiple linear regression showed that the high burden of fast-type idiopathic PVC was associated with higher cortisol levels and lower parasympathetic nervous system tone. The high burden of slow-type idiopathic PVC was associated with lower cortisol levels and lower sympathetic nervous system tone. Meanwhile, in independent-type idiopathic PVC, the high burden was associated with higher cortisol levels and sympathetic nervous system tone as well as lower self-rated health scales.Conclusion: Each PVC circadian type is uniquely related to hypothalamic-pituitary-adrenal axis, autonomic nervous system, and selfrated health. Assessment of PVC circadian type needs to be carried out routinely considering the differences in the underlying associated factors.

Half versus normal saline irrigation during catheter ablation of outflow tract ventricular arrhythmias (HALF): a multi-center, parallel, open-label, randomized controlled study.

Animal studies demonstrated that deeper lesions could be achieved during radio-frequency catheter ablation (RFCA) by using half saline (HS) compared to normal saline (NS) as irrigation. This study sought to compare the efficiency and safety of HS and NS for irrigation during RFCA of idiopathic outflow tract ventricular arrhythmia (OT-VA). In this multicenter, randomized controlled study, 167 patients undergoing RFCA of OT-VA were randomized 1:1 to receive HS- or NS-irrigated ablation. Acute success was defined as the absence of induced targeted premature ventricular contraction (PVC) at the end of the procedure. The 6-month success was defined as a ≥ 80% reduction of pre-procedural PVC burden. There were no differences of baseline characteristics between the HS and NS group. Patients in HS group had shorter total ablation time (259.5 ± 155.5 S vs. 355.6 ± 230.7 S, P = 0.04) than that in NS group. The acute and 6-month success rates were similar between the HS and NS group (92.8 vs. 91.7%, P = 0.79; 90.9 vs. 92.1%, P = 0.79, respectively). No significant difference was observed in the incidence of steam pops between the HS and NS group (2.4 vs. 1.2%, P = 0.62). The ablation using HS irrigation achieved similar success rate and safety compared to that using NS irrigation but was associated with a shorter total ablation time. Chinese Clinical Trial Registry (ChiCTR2200059205).

PO-05-120 CLINICAL SIGNIFICANCE OF POST-ABLATION PREMATURE VENTRICULAR COMPLEXES BURDEN IN PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY UNDERWENT ABLATION FOR VENTRICULAR TACHYCARDIA

A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding PVC burden after catheter ablation for ARVC patients with ventricular tachycardia (VT) at follow-up with ICD recording and its impact on recurrence are scarce. To describe changes in the PVC burden and to assess whether elimination of PVC during substrate modification is associated with recurrence during follow-up in patients with ARVC. In this cohort study, patients with a definite ARVC diagnosis, VT, and ICD underwent ablation were enrolled. The variables retrieved at ICD recording before and after ablation, baseline characteristics, and electrophysiological parameters were extracted for analysis. The association between the parameter and recurrent sustained VA after ablation was assessed using a multivariate logistical model. A total of 38 patients and 65 procedures were enrolled for this study. The VT/VF burden was suppressed after ablation. Recurrence of sustained VA were recorded in 26 procedures. The high mean PVC burden and the presence of NSVT in the ICD recording (3 months post-ablation) was the only parameter associated with recurrence. After multivariate analysis, the PVC burden more than 920 beats/day (obtained from ROC curve) was the only independent predictors for recurrence (HR: 4.314 (95% CI =2.087-9.920), p<0.001). Despite successful ablation in the patients with ARVC, the post-ablation PVC burden could predict the VT/VF recurrence. Aggressive strategy with PVC elimination in addition to substrate modification might be considered.

PO-02-183 ATRIO-VENTRICULAR DISSOCIATION IN PREMATURE VENTRICULAR CONTRACTION WITH DIFFERENT COUPLING INTERVALS

The pathophysiology of Premature ventricular contraction (PVC) induced cardiomyopathy (PVC-CM) remains unclear. AV dissociation (AVD) during PVCs is known as atrial contraction at the time of the PVC. AVD has been implicated as a potential trigger and predictor of PVC-CM, especially early AVD since it results in an increase in LA pressure due to mitral valve closure. The goal of this study was to assess AVD during short- and long-coupled PVCs, and its correlation with the development of PVC-CM. Thirty-one canines underwent implantation of 1) a modified pacemaker to reproduce RV apical PVCs and 2) a telemetry device with a bipole implanted in the LA appendage and RV to record local electrograms and assess AVD during PVCs. Animals were randomized to short-coupled (200ms, n=14), long-coupled (330ms, n=8) bigeminal PVCs, or no PVCs (sham, n=11). AVD was categorized as absent (no P wave during QT interval), early (P wave present between QRS and the peak of the T wave of PVC), or late AVD (P wave between peak and end of T wave of PVC). AVD for four 1-minute segments (6 AM, 12 PM, 6 PM, and 12 AM) for 24 hours and LV ejection fraction were assessed after weeks 1, 4, and 12 of bigeminal PVCs. Ponemah software was used for HR analysis to calculate the minimum, maximum, and average HR and PVC burden. Overall AVD was similar between short- and long-coupled PVCs throughout the 12 weeks (Panel A). Short-coupled PVCs had 35% and 21% of early and late AVD, respectively and no AVD in 44%. Long-coupled PVCs had 50% and 13% of early and late AVD, respectively, without AVD in 37% (Panel B). The early AVD was significantly higher in long-coupled PVCs compared to short-coupled PVCs (50% vs. 35%, Two-Way ANOVA P<0.001), while late AVD was higher in short-coupled PVCs compared to long-coupled PVCs (22% vs. 13%, Two-Way ANOVA, p=0.018) (Panel A &C). Neither short nor long-coupled PVCs showed a significant correlation between AVD and reduction in LVEF at 12 weeks (r=0.09, r=0.06 with p=0.5, p=0.8, respectively). The short- and long-coupled PVCs had increased HR relative to the sham groups (121 vs. 105 vs. 83, Two-Way ANOVA p<0.001). Moreover, HR was significantly higher in short-coupled PVCs than in Long-coupled PVCs (121 vs. 105, Two-Way ANOVA p< 0.001). Early AVD is more pronounced in long-coupled PVCs. AVD does not predict the development of PVC-CM regardless of PVC coupling interval, suggesting that AVD does not play a role in the pathophysiology of PVC-CM.

59. Differential Profiles of Cortisol, Components of Autonomic Nervous System, and Self-Rated Health in Predicting Circadian Variability of Idiopathic Premature Ventricular Contraction Burden

ABSTRACT: Premature ventricular contraction (PVC) patients exhibit specific circadian patterns, yet the lack of circadian rhythm increases the risk of cardiomyopathy. To fully understand the three types of PVC circadian rhythms, we must therefore understand the mechanism of circadian variability, not just of PVC burden. Reflecting on 65 idiopathic PVC patients collecting saliva for cortisol and norepinephrine levels three times daily, undergoing a 24-hour Holter examination, and reporting their morning, afternoon, and evening self-rated health scales; this paper indicates pathways in which psycho-neuro-endocrine physiology and circadian variability in frequency of PVC burden are embodied. Higher cortisol levels and lower parasympathetic nervous system tone are at higher risk of higher burden of fast-type idiopathic PVC. Lower cortisol levels and lower sympathetic nervous system tone are at higher risk of higher burden of slow-type idiopathic PVC. Higher cortisol levels and sympathetic nervous system tone as well as lower self-rated health scales are at higher risk of higher burden of independent-type idiopathic PVC.

Idiopathic Ventricular Tachycardia: Good Prognosis but Debilitating Symptoms

Ventricular arrhythmias may occur in patients without anatomical heart abnormalities, a condition that is known as idiopathic ventricular arrhythmias. The most common form originates at the level of the outflow tracts. It can manifest as PVCs, non-sustained ventricular tachycardia (VT), and sustained VT. A 52-year-old female patient was admitted for 2 episodes of syncope related to a high burden of premature ventricular contractions (PVCs) and several episodes of VT with the same QRS morphology as the PVCs. A diagnosis of sustained monomorphic VT was formulated in a patient with no structural heart disease and a normal ejection fraction. Antiarrhythmic drugs such as metoprolol, propafenone, and amiodarone failed to reduce the number of PVCs, hence catheter ablation was suggested to the patient. The patient consented to the treatment, and following catheter ablation, the patient no longer experienced syncope. The 24-hour Holter ECG monitoring revealed no PVCs or VTs. PVCs and VTs from the RVOT are typically benign with a good prognosis. Catheter ablation should be employed as the definitive treatment for RVOT-VT, as our case demonstrates only partial response to antiarrhythmic drugs.

Alterations of sarcoplasmic reticulum-mediated Ca2+ uptake in a model of premature ventricular contraction (PVC)-induced cardiomyopathy.

Premature ventricular contractions (PVCs) are the most frequent ventricular arrhythmias in the overall population. PVCs are known to acutely enhance contractility by the post-extrasystolic potentiation phenomenon, but over time persistent PVCs promote PVC-induced cardiomyopathy (PVC-CM), characterized by a reduction of the left ventricular (LV) ejection fraction. Ca2+ cycling in myocytes commands muscle contraction and in this process, SERCA2 leads the Ca2+ reuptake into the sarcoplasmic reticulum (SR) shaping cytosolic Ca2+ signal decay and muscle relaxation. Altered Ca2+ reuptake can contribute to the contractile dysfunction observed in PVC-CM. To better understand Ca2+ handling using our PVC-CM model (canines with 50% PVC burden for 12weeks), SR-Ca2+ reuptake was investigated by measuring Ca2+ dynamics and analyzing protein expression. Kinetic analysis of Ca2+ reuptake in electrically paced myocytes showed a ~ 21ms delay in PVC-CM compared to Sham in intact isolated myocytes, along with a ~ 13% reduction in SERCA2 activity assessed in permeabilized myocytes. Although these trends were not statistically significant between groups using hierarchical statistics, relaxation of myocytes following contraction was significantly slower in PVC-CM vs Sham myocytes. Western blot analyses indicate a 22% reduction in SERCA2 expression, a 23% increase in phospholamban (PLN) expression, and a 50% reduction in PLN phosphorylation in PVC-CM samples vs Sham. Computational analysis simulating a 20% decrease in SR-Ca2+ reuptake resulted in a ~ 22ms delay in Ca2+ signal decay, consistent with the experimental result described above. In conclusion, SERCA2 and PLB alterations described above have a modest contribution to functional adaptations observed in PVC-CM.

Abstract 9547: Demographic Differences in Patients With Frequent PVCs and Cardiomyopathy in the General Population Receiving Ambulatory Holter Monitoring

Introduction: A high burden of premature ventricular contractions (PVCs) has been associated with the development of cardiomyopathy (CM) and heart failure. However, the prevalence of high PVC burden and cardiomyopathy (CM) remain unclear. Hypothesis: The prevalence of high PVC burden (&gt;5%) is underestimated in patients receiving Holter monitors and those with CM (LVEF &lt;50%). Methods: A prospective multicenter clinical study of consecutive patients undergoing ambulatory Holter monitors (24 hours up to 2-weeks), between July 2018 through June 2020 were reviewed. Demographic data, PVC burden and LV function were collected within 6 months of Holter placement. Results: A total of 8 centers across the US provided a total of 6,808 patients with ambulatory Holter monitors. Four and 5% of patients undergoing Holter monitors had a PVC burden of 6-10% and &gt;10%, respectively. A total of 3,938 patients had assessment of LVEF within 6 months of Holter, of which 634 (16%) had CM and 173 (4%) had both CM and PVCs &gt; 5%. Males were more likely to have had LVEF assessment than females (58% vs. 55%, P=0.013). Table summarizes demographics in the overall population based on PVC burden and presence of CM. High PVC burden (&gt;5%) was more prevalent in older, male, and White patients. In an ordinal logistic regression to assess PVC burden with gender separately for LVEF &lt; or &gt; 50%, females were found to have a higher PVC burden in the population with preserved LVEF (OR=1.59, 95% CI: 1.13, 2.22) but not with CM (LVEF &lt; 50%, OR=1.13, 95% CI=0.97, 1.32). Females had a lower prevalence of high PVC burden (&gt;5%) than males (7% vs. 11%; p&lt;0.001), including among those with CM (23% vs. 29%, p=0.1). Conclusions: High PVC burden and CM are quite prevalent in the population undergoing Holter monitors. Older age is associated with higher PVC burden but no age difference is present between different PVC burdens in patients with CM. Females have a lower prevalence of high PVC burden (&gt;5%) and combined high PVC burden and CM than males.

Abstract 14559: Anti-Arrhythmic Effects of Exosomes Isolated From Cardiosphere-Derived Cells in Rats With Heart Failure and Preserved Ejection Fraction

Introduction: Cardiosphere-derived cells (CDCs) reverse electrical remodeling and reduce inducible ventricular arrhythmias in rats with heart failure and preserved ejection fraction (HFpEF). Exosomes isolated from CDCs (CDCexo) have anti-arrhythmic effects in various animal models but have not been tested in models of HFpEF. Hypothesis: CDCexo, when given intravenously, reverse electrical remodeling and reduce spontaneous ventricular arrhythmias in rats with HFpEF. Methods: Dahl salt-sensitive rats were fed high-salt diet (containing 8% NaCl) to induce HFpEF from 7 weeks of age. Ambulatory electrocardiogram (ECG) devices were implanted in the peritoneum at 13 weeks of age to monitor spontaneous ventricular arrhythmias. Exosomes were harvested from media conditioned by human CDCs after 48 hours of exposure to hypoxia. Echocardiogram-verified HFpEF rats (at 14 weeks of age) were injected via tail vein with human CDCexo (n=8) vs. vehicle (IMDM media, n=8) weekly for 4 weeks. ECG parameters and spontaneous development of ventricular arrhythmias were compared between the two groups. Results: QTc interval was reduced in CDCexo-injected HFpEF rats compared to vehicle-injected HFpEF rats (262±15 ms vs. 287±25 ms, p=0.0001). Two of the eight HFpEF rats injected with vehicle showed a maximal premature ventricular contraction (PVC) burden per minute of 50% while only one HFpEF rat injected with CDCexo manifested 25% maximal PVC burden per minute. Five of eight HFpEF rats injected with vehicle showed non-sustained ventricular tachycardia (VT) while only one HFpEF rat infused with CDCexo developed non-sustained VT. One rat in the vehicle group undergoing telemetry monitoring died suddenly and the cause of death was sustained VT degenerating into ventricular fibrillation (VF). The number of VT/VF episodes per rat (including non-sustained VT and sustained VT/VF) was reduced in the CDCexo group compared to the vehicle group (0.4 [0-3] vs. 13 [0-56] episodes per rat, p=0.0443). Conclusions: CDCexo recapitulated the beneficial effects of CDCs in HFpEF rats: reversing electrical remodeling and reducing ventricular arrhythmias. More importantly, an intravenous delivery route was effective for CDCexo to confer their salutary effects to rats with HFpEF.

Association between ventricular premature contraction burden and ventricular repolarization duration.

Premature ventricular contraction is generally known as benign in the absence of structural heart disease; however, premature ventricular contraction-induced left ventricular systolic dysfunction or ventricular arrhythmias are defined in some cases. Ventricular repolarization duration differs between myocardial cells, which causes myocardial electrical heterogeneity and is thought to be responsible for ventricular arrhythmias. In our study, we aimed to evaluate the association of ventricular repolarization parameters including Tp-Te interval, Tp-Te/QT ratio, and QRS-T angle with premature ventricular contraction frequency in patients with premature ventricular contraction burden. A total of 80 subjects who were admitted to our cardiology department and underwent 24-h electrocardiography Holter monitoring were included. Patients were divided into two groups: group 1 is defined as premature ventricular contraction burden that had frequent premature ventricular contraction ≥1% in 24-h Holter monitoring, and group 2 is defined as rare premature ventricular contraction <1% in 24-h Holter monitoring. Tp-Te interval and Tp-Te/QT ratio are statistically significantly prolonged in the premature ventricular contraction burden group than in the control group (85.3±13.9 vs. 65.7±11.9, p<0.001; 0.19±0.03 vs. 0.15±0.02, p<0.001, respectively). QRS-T angle was statistically significantly abnormal in the premature ventricular contraction burden group (p=0.024). Increased Tp-Te interval and widened QRS-T angle are associated with ventricular arrhythmias and might be used for the prediction of premature ventricular contraction burden in patients with premature ventricular contraction in electrocardiography in the absence of 24-h Holter monitoring.