Premature Ventricular Contractions Group Research Articles

Prevalence of frequent premature ventricular contractions and left-ventricular systolic dysfunction in patients receiving Holter monitoring.

Premature ventricular contractions (PVCs) are frequently observed with left ventricular (LV) systolic dysfunction, although the prevalence of these associated conditions in the general population remains unknown. We sought to understand the prevalence of frequent PVCs (defined PVCs > 5%) and high burden PVCs (defined PVCs > 10%) and LV systolic dysfunction in patients receiving ambulatory Holter monitors (HM). A prospective multicenter (eight US medical centers) cross-sectional study collected demographic and PVC burden data from consecutive patients undergoing 24-h, 48-h, and 14-day HM (July 2018-June 2020). Left ventricle ejection fraction (LVEF) data was collected if obtained within 6 months of HM. Four PVC burden groups were analyzed (<1%, 1%-5%, 5.1%-10%, and >10% burden) and stratified by normal LVEF (≥50%) or presence LVEF < 50%. The prevalence of PVC burden of 5.1%-10% and >10% was 4% and 5%, respectively in the population undergoing HM (n = 6529). Age was significantly different between PVC groups (p < .001). In those with LVEF assessment (n = 3713), the prevalence of LVEF < 50% and both LVEF < 50% and PVC > 5% was 16.4% and 4.2%, respectively. The prevalence of PVC > 5% and PVC > 10% in patients with LVEF < 50% was 26% and 16%, respectively. PVC > 5% were more prevalent in older, male, and Caucasians (p < .001). Females had a lower prevalence of PVC > 5% than males (6% vs. 11%; p < .001), but not among those with LVEF < 50% (24% vs. 26%, p = .10). PVC > 5% and PVC > 10% and LVEF < 50% are prevalent in patients undergoing HM. PVC > 5% are associated with older age. Females have a lower prevalence of PVC > 5% than males but similar combined PVC > 5% and LVEF < 50%. gov identifier: NCT03228823.

Alterations of Myocardial Mitochondrial Morphology and Function in a Canine Model of Premature Ventricular Contractions-Induced Cardiomyopathy.

Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM. Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05). We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.

Association between excess catecholamine synthesis and polymorphic premature ventricular contraction

BackgroundThe reasons for the etiology of premature ventricular contractions (PVCs) are not specifically known. Many patients are resistant to medical treatment, and a factor that would predict response to medical treatment cannot be identified. This study aims to investigate if a high catecholamine level results in polymorphic PVC. MethodsThis study was obtained by prospective data registry analysis. A total of 100 patients, 50 from the PVC group, and 50 from the control group have been evaluated. The participants who were included in the patient group had a polymorphic PVC of 5% or more in their 24-h Holter evaluations. Metanephrine showing the level of adrenaline and normetanephrine, showing the level of noradrenaline levels have been measured from these urine samples. ResultThere was no difference between the two groups in terms of biochemical and essential characteristics. Normetanephrine level has been significantly higher in the PVC group compared to the control group (323.9 ± 208.9 μg to 129.25 ± 67.88 μg; p < 0.001). Similarly, metanephrine level has also been higher in the PVC group (124.75 ± 82.43 μg to 52.615 ± 36,54 μg; p < 0.001). A positive and moderate correlation has been identified between the number and ratio of PVC and the metanephrine and normetanephrine levels. ConclusionIn this study, we found that the catecholamine levels were higher in the polymorphic PVC group than in the healthy volunteers. Also, an increase in the number and rate of PVC has been observed as the catecholamine levels increased. Clinical Trial RegistrationUrine Levels of Metanephrine and Normetanephrine in Patients With Frequent PVC; ClinicalTrials.gov number NCT03447002

Worldwide Experience With an Irrigated Needle Catheter for Ablation of Refractory Ventricular Arrhythmias: Final Report

BackgroundWe previously reported feasibility of irrigated needle ablation (INA) with a retractable 27-G end-hole needle catheter to treat nonendocardial ventricular arrhythmia substrate, an important cause of ablation failure. ObjectivesThe purpose of this study was to report outcomes and complications in our entire INA-treated population. MethodsPatients with recurrent sustained monomorphic ventricular tachycardia (VT) or high-density premature ventricular contractions (PVCs) despite radiofrequency ablation were prospectively enrolled at 4 centers. Endpoints included a 70% decrease in VT frequency or PVC burden decrease to <5,000/24 h at 6 months. ResultsINA was performed in 111 patients (median: 2 failed prior ablations, 71% nonischemic heart disease, and left ventricular ejection fraction 36% ± 14%). INA acutely abolished targeted PVCs in 33 of 37 patients (89%), and PVCs were reduced to <5,000/day in 29 patients (78%). During 6-month follow-up, freedom from hospitalization was observed in 50 of 72 patients with VT (69%), and improvement or abolition of VT occurred in 47%. All patients received multiple INA applications, with more in the VT group than in the PVC group (median: 12 [IQR: 7-19] vs 7 [5-15]; P < 0.01). After INA, additional endocardial standard radiofrequency ablation was required in 23% of patients. Adverse events included 4 pericardial effusions (3.5%), 3 cases of (anticipated) atrioventricular block (2.6%), and 3 heart failure exacerbations (2.6%). During 6-month follow-up, 5 deaths occurred; none were procedure-related. ConclusionsINA achieves improved arrhythmia control in 78% of patients with PVCs and avoids hospitalization in 69% of patients with VT refractory to standard ablation at 6-month follow-up. Procedural risks are acceptable. (Intramural Needle Ablation for Ablation of Recurrent Ventricular Tachycardia, NCT01791543; Intramural Needle Ablation for the Treatment of Refractory Ventricular Arrhythmias, NCT03204981)

Premature ventricular contractions: the role in arterial atherosclerosis pathogenesis

Abstract Funding Acknowledgements Type of funding sources: None. In the list of reasons of atherosclerosis, there are no premature ventricular contractions (PVCs). Purpose To study the main arteries hemodynamics in patients with PVCs and to determine their influence on the atherosclerotic process. Methods We studied 286 patients with PVCs (group 1 (142) – patients with PVCs less 3000 per 24 hours, 2 (144) – more 3000 per 24 hours. Groups were similar in age, gender, comorbidities. By Doppler-ultrasound and shygmography we determined the parameters of heart biomechanics and main arteries kinetics (common carotid, posterior tibial artery): speed, acceleration, power, work in each phase of heart cycle in systole and diastole, the periods of dominance of outflow over inflow. We valued the contribute to the circulation of the PVs and first post-extrasystolic contraction. The volume of cardiac output and transmitral blood flow were measured by echocardiography. We identified the moment of extrasysyoles' appearance by apex-cardiography and ECG. We classified the PVCs up to the moment of their appearance in cardio cycle: before the mitral valve opening; in rapid ventricular filling phase before or after the transmitral blood flow peak; in slow ventricular filling phase; others (group, allorhythmia). Results We identified the following hemodynamic effects of PVCs. 1) The main role in hemodynamic and kinetics changes play the time of PVC’ appearance in cardio cycle and the ability of the first post-extrasystolic contraction to reestablish an adequate resulting blood flow. The maximums of parameters were in first post-extrasystolic contraction in PVCs before the mitral valve opening and before the transmitral peak flow. 2) The prevalence of atherosclerotic process was observed in group 2 (p&amp;lt;0,05). (Carotid bifurcation stenosis hemodynamically not significant in 42 patients in group 2 vs 26 in group 1, significant – 28 vs 8, lower extremities arteries stenoses 37 vs 17, coronary arteries stenoses 74 vs 35, renal arteries stenoses 6 vs 1). 3) Additional stretching of arteries in the first post-extrasystolic pressure wave. It makes conditions for acute and chronic arteries traumatism. 4) Mechanic damage of endothelium and as a result lipid deposition. The "weak places" – are the places of the main effect of the first post-extrasystolic hydraulic shock: aorta arch in large radius, carotid bifurcation, aorta bifurcation. 5) Appearing the stand waves, interferention and diffraction in the places of already existing atheromas. Atheroma is deforming, the integrity of atheroma’s cover is violated and there’re appearing the atheroma’s complications: dissections, wall thrombus of hemodynamically important stenosis. Conclusion PVCs change intra-arterial hemodynamics and can cause the mechanical injury of intima, as well as the injury of existing atherosclerotic plaques that can lead to progressing of atherosclerosis. We suppose to include the PVCs in the list of risk factors of atherosclerosis.

Angiogenesis and activated fibroblast in a model of premature ventricular contraction-induced cardiomyopathy.

Premature ventricular contractions (PVCs) are the most common ventricular arrhythmia in the elderly, and when frequent, can result in PVC-induced cardiomyopathy (PVC-CM). PVC-CM canine model showed eccentric hypertrophy and fibrosis in the left ventricle (LV). The underlying structural and molecular mechanism behind this LV remodeling is unknown. In situ structural adaptations of the LV tissue and the activation of the VEGF/ERK1/2 signaling pathway were studied in the PVC-CM model. Pacemakers were implanted in healthy canines where PVCs were enabled only in the PVC-CM group (50% of PVC burden, 200-220-ms coupling interval) for 12 weeks. Fixed LV longitudinal- and cross-sections were stained with anti-α-SMA antibody, a marker of activated fibroblast (myofibroblasts) and smooth muscle cells (blood vessels), and WGA-AF633 (a marker of cell membranes). Confocal images were analyzed using artificial intelligence (AI)-powered autonomous software, AIVIA. Western blot (WB) analysis was used to study the pro-angiogenic signaling pathway and proteins associated with fibroblast activation. In situ analysis showed a significant increase in the total area and number of blood vessels, along with an increase in activated fibroblasts in PVC-CM LV sections. Also, the PVC group showed a 30% increase in the number of activated fibroblasts per cardiomyocyte compared with the sham group. The endothelial marker, eNOS, and IL-1β, a cytokine involved in fibroblast activation, were elevated in the PVC-CM group. Additionally, the VEGF-A, VEGF-B, and VEGF receptor 2 were upregulated in PVC-CM vs Sham; downstream ERK1/2 was hyperphosphorylated and overexpressed, and MMP9 (marker of fibroblast activation linked to this pathway) was elevated in PVC-CM vs Sham. In conclusion, activated fibroblasts and angiogenesis are a feature of the cardiac LV hypertrophic remodeling in PVC-CM.

Prognostic implication of premature ventricular contractions in patients without structural heart disease.

Premature ventricular contractions (PVCs) are a common form of arrhythmia associated with an unfavourable prognosis in patients with structural heart disease. However, the prognostic significance in absence of heart disease is debated. With this study, we aim to investigate whether subjects with PVC, without structural heart disease, have a worse prognosis than the general population. Patients evaluated for PVC at a secondary care centre in Stockholm County from January 2010 to December 2016 were identified. We included patients without history of previous heart disease who had undergone echocardiography and exercise test with normal findings. Based on sex and age, we matched the PVC cohort to a four times bigger control group from the general population and compared the outcome in terms of mortality and cardiovascular morbidity during a median follow-up time of 5.2 years. We included 820 patients and 3,264 controls. Based on a non-inferiority analysis, the PVC group did not have a higher mortality than the control group (0.44, CI 0.27-0.72). Sensitivity analysis with propensity score matching confirmed this result. PVC patients, who after thorough evaluation showed no signs of structural heart disease, did not have a worse prognosis when compared to an age- and sex- control group based on the general population.

Evaluation of patients with high burden of premature ventricular contractions by comprehensive transthoracic echocardiography.

BackgroundThe prevalence and prognosis of premature ventricular contractions (PVCs) among individuals without structural heart disease are uncertain. Standard transthoracic echocardiography is a common method in evaluation of underlying cardiovascular disease and is recommended as a diagnostic method in PVC patients. However, it is unclear whether comprehensive echocardiographic examination can identify pathological findings in PVC patients with a normal standard echocardiogram.MethodWe included forty consecutive patients with a high PVC burden (>10,000 PVCs/day) and normal findings at a standard echocardiogram and exercise test. All subjects were investigated by a comprehensive echocardiographic examination using parameters usually not included in a routine work-up. We compared the results with 22 age and sex-matched controls.ResultsIn six additional parameters–global longitudinal strain, right ventricular strain, septal-lateral delay, ventricular-arterial coupling, integrated backscatter and left atrial activation time–a statistically significant difference was shown between PVC patients and controls. Among these parameters, global longitudinal strain had a high reliability between operators.ConclusionsDespite normal findings at standard echocardiography, the PVC group showed signs of impaired heart function when more comprehensive echocardiography parameters were used.

Left ventricular dyssynchrony as marker of early dysfunction in premature ventricular contraction-induced cardiomyopathy.

BackgroundStrain imaging has been suggested as a tool to detect early left ventricular (LV) dysfunction due to frequent premature ventricular contractions (PVCs) in patients with preserved LV ejection fraction (EF). However, the progression of intraventricular dyssynchrony (IVD), radial, and circumferential strain (RS, CS) in PVC-cardiomyopathy (CM) are unknown. The aim of this study was to elucidate the progression patterns of CS, IVD, and electro-mechanical latency (EML) in PVC-CM.Methods and resultsPacemakers were implanted in 20 canines to reproduce ventricular bigeminy at 200ms (PVCs n = 11) for 12 weeks and compared to a sham group (n = 9). We obtained echocardiograms at baseline, 4-, 8- and 12-weeks. RS and CS were obtained at the LV mid-cavitary level. IVD was defined as the time between the earliest and latest peak RS. EML was defined as the time between the onset of QRS and the earliest peak RS. LVEF (62 ± 5 to 42 ± 7%, p < 0.01), CS (–18 ± 3 to –12 ± 3, p < 0.01), and EML (219 ± 37 to 283 ± 46ms, p = 0.02) changed significantly in the PVC group. Peak CS (–18 ± 3 to –14 ± 4, p = 0.02) and IVD (49 ± 31 to 122 ± 103, p = 0.05) had a significant change at 4-weeks despite preserved LVEF (51 ± 5%). IVD normalized while EML increased at weeks 8 and 12.ConclusionOur findings consolidate the existing theory that changes in strain precede changes in LVEF in PVC-CM. While IVD becomes abnormal early in the development of PVC-CM, it pseudo-normalizes at advanced stages due to further increases in EML suggestive of cardiac contractility remodeling. These findings are consistent with recent published data where abnormal LV mechanics could be part of a substrate that can predispose to worse outcome in PVC-Cardiomyopathy.

Frontal QRS-T Açısı İle Ambulatuar 24 Saat Holterde Prematür Ventriküler Kontraksiyon Yükü Arasındaki İlişki

Aim: Frequent premature ventricular contractions (PVCs) can cause impaired ventricular function or dilatation of ventricular cavities. The frontal plane QRS-T [f(QRS-T)] angle is an indicator of instability in the electrophysiological properties of the myocardium and is associated with arrhythmias. The present study aimed to investigate whether f(QRS-T) angle, as a marker of ventricular repolarization heterogeneity, predicts premature ventricular contraction burden in ambulatory 24-hour Holter.Methods: The study included 100 patients. The patients were divided into two groups as ‘frequent PVC’ and ‘seldom PVC’ according to their PVC burden in 24-hour Holter monitoring. Laboratory and some ambulatory electrocardiography parameters, including frontal plane QRS-T angle, were compared between the two groups.Results: Frontal QRS-T angle (63.34±37.86° vs 23.46±14.29° p&amp;lt;0.001) was found to be wider in the Frequent PVC group. F(QRS-T) angle of ≥ 34° had a sensitivity of 82.2% and a specificity of 80% in indicating PVC load (AUC: 0.887 (0.824-0.950). In addition, a positive correlation was found between PVC burden and f(QRS-T) angle (r:0.429 p&amp;lt;0.001).Conclusion: The widening of f(QRS-T) angle could perhaps be considered as a surrogate marker of increased PVC burden in 24-hour Holter monitoring. Measuring f(QRS-T) angle in 12-lead ECG in patients with PVC may be a warning sign for increased PVC burden.

Abstract 155: Gender Differences In Patients With Ventricular Arrhythmias Undergoing Catheter Ablation

Significant differences in the clinical presentation and outcomes of cardiovascular diseases in men and woman have been described in the last few decades, including in management of cardiac arrhythmias. Recently, catheter ablation for ventricular arrhythmia (VA) has been shown to be highly effective at reducing ventricular tachycardia (VT) and premature ventricular contractions (PVC) burden, including reduction of VA episodes. Much of the published data has identified risk factors for VA recurrence, such as low LVEF, but have not included enough women for meaningful comparison of gender-based differences. The goal of this study was to examine gender differences in patients with ventricular arrhythmias who have undergone VA ablation. We conducted a retrospective analysis on a cohort of 115 patients receiving VA ablation at a tertiary hospital (54 pts for VT and 63 pts for PVC, 76 males and 39 females) to identify gender differences in patient characteristics at time of ablation. In the total group, there were 76 (66.1% males and 39 (33.9%) females, mean age - 59.6 +14.8 years; av. LVEF = 46.6% + 13.63%). Females were younger (52.2 vs 63.9 years) and had higher LVEF (53.7% vs 43.1%) as compared to men. History of pre-procedure ICD, ischemic heart disease and procedures, such as CABG or stent placement, were higher in men. Also, more males were diagnosed with hypertension and dyslipidemia. VT patients had lower LVEF and a higher proportion of males with worse pre-procedure characteristics than PVC patients. Hypertension and older age were observed among males in both PVC and VT groups. Overall, study results show female patients had less severe comorbidities, younger age and better LVEF. These findings can reflect differences in VA ablation outcomes as well as the selection of treatments for patients with VA.

The Tp-e/QT ratio as a predictor of nocturnal premature ventricular contraction events in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is significantly associated with a higher risk of ventricular arrhythmia (VA). QT, the Tp-e/QT ratio, and QT dispersion (QTd) are used to evaluate myocardial repolarization and are highly correlated with VA. The aim was to evaluate the predictive value of the Tp-e/QT ratio and other electrocardiogram (ECG) parameters for nocturnal premature ventricular contractions (PVCs) in patients withOSA. We retrospectively analyzed data from patients withOSA and conducted a 1:1 matched cohort study. Patients diagnosed with OSA whomet our criteria for the PVC group, and sex- and age-matched patients withOSA who met our criteria for the control groupwere enrolled in the study. The Tp-e, Tp-e/QT ratio, corrected QT interval (QTc), corrected Tp-e interval (Tp-ec), and QTd were measured, calculated and analyzed. Patients in the PVC group(n = 31) showed a greater Tp-e, Tp-ec, QTc, Tp-e/QT ratio, and QTd than patients in the control group(n = 31). In the univariate binary logistic regression analysis, higher Tp-ec (OR: 1.025; P = 0.042), QTc (OR: 1.014; P = 0.036), Tp-e/QT ratio (OR: 1.675; P < 0.001), and QTd (OR: 1.052; P = 0.012) values were all significantly associated with nocturnal PVCs. In multivariate analysis and receiver operating characteristic analysis, a higher Tp-e/QT ratio (OR: 2.168; 95% CI: 0.762-0.952; P < 0.001) was an independent predictor of nocturnal PVCs. The QTc, Tp-e/QT ratio, and QTd in patients withOSA with nocturnal PVCs were significantly increased compared with those in patients without nocturnal PVCs. A prolonged Tp-e/QT ratio was an independent predictor of nocturnal PVCs in patients with OSA.

Assessment of functional and structural echocardiography parameters in patients with frequent premature ventricular contractions without structural heart disease.

Premature ventricular contractions (PVCs) are early depolarizations of the myocardium which originate from the ventricle. PVCs have previously been considered a benign condition. The clinical significance of PVCs in patients without structural heart disease is controversial. In this cross-sectional study, patients with a palpitation complaint who underwent electrocardiography (ECG) Holter recording for 48 hours were analyzed. Patients with frequent PVCs (more than ten times in 1 hour) were identified and enrolled in the study. 26 patients were in the PVC group, and 26 patients were in the control group without PVC. The identified patients underwent an echocardiographic examination with strain modality. There were 15 women (57.7%) in the PVC group and 17 women (65.4%) in the control group (P = 0.57). Two patients in the PVC group and three patients in the control group were hypertensive (P > 0.99). There was only one patient with diabetes in PVC and control group (P > 0.99). There were two smokers in the PVC group, whereas there was no smoker in the control group (P = 0.49). In comparison between two groups, patients with frequent PVCs had significantly larger left ventricular end-diastolic volume index (LVEDVI) (P = 0.048) along with lower left ventricular ejection fraction (LVEF) (P = 0.011), lower (more positive) left ventricular global longitudinal strain (LVGLS) (P = 0.001), and lower peak systolic mitral annular velocity (S') (P = 0.045). The left atrial volume index (LAVI) was significantly larger in the PVC group (P = 0.001). In speckle tracking echocardiography (STE) parameters, global peak atrial longitudinal strain (PALS) (P = 0.001) and peak atrial contraction strain (PACS) (P = 0.001) were significantly lower and time to peak longitudinal strain (TPLS) (P = 0.002) was significantly higher in the PVC group. In this study, left atrial (LA) and left ventricular (LV) function and geometry were adversely affected by frequent PVCs. Early diagnosis of these effects is possible with echocardiography along with strain analysis. It can guide the timely treatment of PVC to avoid the harmful effects of frequent PVCs on the heart.

Premature cardiac beats in children with structurally normal heart: autonomic dysregulation.

Premature ventricular contractions and supraventricular contractions are common rhythm disorders requiring comprehensive investigation in children. The aim of the study was to evaluate the heart rate variability (HRV) in premature ventricular contractions (PVCs) and supraventricular contractions (PSVCs) in children. The study compared the characteristics of HRV in 175 children with PVCs and 160 children with PSVCs who underwent 24-h Holter monitoring, with 101 healthy children. Significant differences were found between standard deviation of all normal RR intervals (SDNN), standard deviation of average RR intervals in all 5 min segments of registration (SDANN), root mean square of the successive differences (rMSSD), and the proportion of NN50 divided by total number of NNs (pNN50) values of the patient and control groups. The PVCs group had a significantly lower high frequency (HF) and higher low frequency (LF)/HF ratio and the PSVCs group had a significantly higher LF and higher LF/HF ratio compared to the control group. No significant correlation existed between frequency and the SDNN index, rMSSD, and pNN50 values of the PVCs group. The receiver operating characteristics analysis showed a significantly changed LF/HF ratio when premature contractions exceeded 60 beats per hour in children with PVCs. This study indicated an increased sympathetic tone and a significantly decreased vagal tone in children with PVCs and PSVCs. HRV can be used increasingly as a non-invasive method in the follow-up of children with premature cardiac contractions.

Abstract 13931: Upregulation of the AKT/mTOR Pathway in Premature Ventricular Contractions (PVC)-Induced Cardiomyopathy

Introduction: Premature ventricular contractions (PVCs) are early ventricular depolarizations that, if frequent, can be associated with PVC-induced cardiomyopathy (PVC-CM). PVC-CM in our translational model is characterized by LV systolic dysfunction and eccentric hypertrophy. However, the mechanisms involved in this LV remodeling remain unknown. Objectives: Evaluate changes in cardiomyocyte size and sarcomere shortening, along with classical molecular pathways involved in pathological or physiological hypertrophy in the PVC-CM model. Methods: Pacemakers were implanted in healthy canines to reproduce 3 months of bigeminal PVCs (50% burden at 200-220 ms coupling interval). Isolated ventricular cardiomyocytes were electrically paced to measure sarcomere length. Formaldehyde-fixed LV sections were stained with WGA-AF633. Expression of β-MHC, ACTA1, ANP, calcineurin, AKT, mTOR, S6, 4EBP1, NFAT and their phosphorylated forms were measured by Western blot. Calcineurin activity was determined by colorimetry. Results: Cardiomyocyte area was larger in PVC group vs. sham (357.4 ± 12.9 μm 2 n= 121 vs. 271.8 + 7 μm 2 n = 161, p&lt;0.001). Time to peak sarcomere contraction was longer in the PVC group (124.9 + 25.2 ms, n=101 vs 116.2 + 27.4 ms, n=61, p&lt;0.05), whereas maximal cell shortening was similar between groups. Western blot analyses (n=6) showed significant increases in AKT expression (1 + 0.18 vs 1.6 + 0.43, p&lt;0.001), and in its downstream effectors, S6 (1 + 0.26 vs 1.46 + 0.4, p&lt;0.05) and 4EBP1 (1 + 0.3 vs 1.57 + 0.38, p&lt;0.001) in the PVC group, without changes in mTOR. On the contrary, PVC group displayed a reduction in phosphorylated AKT (Ser473, 1 + 0.14 vs 0.77 + 0.26, p&lt;0.05) and 4EBP1 (Thr37/46, 1 + 0.15 vs 0.75 + 0.1, p&lt;0.001) without changes in S6 (Ser235/236) or mTOR (Ser2448) phosphorylation. The activity and expression of calcineurin, total and phospho- NFAT, and the expression of β-MHC, ACTA1, and ANP were not different. Conclusion: The pathological calcineurin/NFAT/fetal genes pathway was unchanged in the PVC-induced eccentric hypertrophy. Thus, this hypertrophy is “atypical” characterized by an upregulation of the AKT/mTOR pathway and cellular hypertrophy, together with a paradoxical decrease in contractility and LV systolic dysfunction.

Prolonged Right Ventricular Outflow Tract Endocardial Activation Duration and Presence of Deceleration Zones in Patients With Idiopathic Premature Ventricular Contractions. Association With Low Voltage Areas.

Background and AimsThe wavefront propagation velocity in the myocardium with fibrosis is characterized by the presence of deceleration zones and late activated zones, that are absent in the normal myocardium. Our aim was to study the right ventricular outflow tract (RVOT) endocardial activation duration in sinus rhythm, and assess the presence of deceleration zones, in patients with premature ventricular contractions (PVCs) and in controls.MethodsWe studied 29 patients with idiopathic PVCs from the outflow tract, subjected to catheter ablation that had an activation and voltage map of the RVOT in sinus rhythm. A control group of 15 patients without PVCs that underwent ablation of supraventricular arrhythmias was also studied. RVOT endocardial activation duration and number of 10 ms isochrones across the RVOT were assessed. Propagation speed was calculated at the zone with the higher number of isochrones per cm radius. Deceleration zones were defined as zones with >3 isochrones within 1 cm radius. Low voltage areas were defined as areas with local electrogram with amplitude <1.5 mV.ResultsThe two groups did not differ in relation to age, gender or number of points in the map. RVOT endocardial activation duration and number of 10 ms isochrones were higher in the PVC group; 56 (41–66) ms vs. 39 (35–41) ms, p = 0.001 and 5 (4–8) vs. 4 (4–5), p = 0.001. Presence of deceleration zones and low voltage areas were more frequent in the PVC group; 20 (69%) vs. 0 (0%), p < 0.0001 and 21 (72%) vs. 0 (0%), p < 0.0001. The wavefront propagation speed was significantly lower in patients with PVCs than in the control group, 0.35 (0.27–0.40) vs. 0.63 (0.56–0.66) m/s, p < 0.0001. Patients with low voltage areas had longer activation duration 60 (52–67) vs. 36 (32–40) ms, p < 0.0001, more deceleration zones, 20 (95%) vs. 0 (0%), p < 0.0001, and lower wavefront propagation speed, 0.30 (0.26–0.36) vs. 0.54 (0.36–0.66) m/s, p = 0.002, than patients without low voltage areas.ConclusionRight ventricular outflow tract endocardial activation duration was longer, propagation speed was lower and deceleration zones were more frequent in patients with PVCs than in controls and were associated with the presence of low voltage areas.

Assessment of wavefront propagation speed on the right ventricular outflow tract: deceleration zones associated with the presence of low voltage areas

Abstract Funding Acknowledgements Type of funding sources: None. Background and aims Activation wavefront is rapid and uniform in normal myocardium. Fibrosis is associated with deceleration zones (DZ) and late activated zones. The presence of low voltage areas (LVAs) in the right ventricular outflow tract (RVOT) of patients with premature ventricular contractions (PVCs) from this origin has been described previously. The aim of this study was to evaluate in sinus rhythm, the RVOT endocardial activation duration (EAD) and the presence of DZs, in patients with PVCs and in controls. Methods Consecutive patients with frequent (&amp;gt;10.000/24 h) idiopathic PVCs with inferior axis subjected to ablation that had an activation and voltage map of the RVOT performed in sinus rhythm. A control group of patients without PVCs that underwent ablation of supraventricular arrhythmias was also studied. Patients with structural heart disease, previous ablation or conduction disease were excluded. The RVOT EAD was measured as the time interval between the earliest and the latest activated region. Also evaluated the number of 10 ms isochrones throughout the RVOT and the maximal number of 10 ms isochrones within 1 cm, and a DZ was defined as a zone with &amp;gt; 3 isochrones within 1 cm. Low voltage areas (LVA) were defined as areas with local electrogram amplitude &amp;lt;1.5 mV. Results 42 patients, 29 in the PVC group and 13 control subjects. The site of origin of the PVCs was the RVOT in 23 patients and the LVOT in 6. The characteristics of the two groups are displayed in the Table. Patients with PVCS had longer RVOT EAD, total number of isochrones and presence of DZ was also significantly higher (See table). LVAs were more frequent in PVCs from the RVOT than from the LVOT (83% vs 33%, p = 0.033). Patients with LVA had longer EAD 60 (52-67) vs 36 (34-40) ms, p &amp;lt; 0.0001 (Figure A) and more DZ than patients without LVA 95% vs 0%, p &amp;lt; 0.0001 (Figure B and C). Conclusions The velocity of the wavefront propagation was slower and DZs were more frequently present in patients with PVCs and were associated with presence of LVAs. All sampleN= 42PVCsN = 29ControlsN = 13p-valueAge in years, median (Q1-Q3)56 (35-65)58 (38-66)53 (28-67)0.648Male gender, n (%)19 (45)14 (48)5 (39)0.401Nº points in the map, median (Q1-Q3)410 (338-589)467 (345-660)345 (333-465)0.056Activation duration in ms, median (Q1-Q3)41.8 (36-61)56 (41-66)39 (35-41)0.001Nº isochrones, median (Q1-Q3)4 (4-6)5 (4-6)4 (4-4)0.037Presence of DZs, n (%)20 (48)20 (69)0 (0)&amp;lt;0.0001Presence of LVAs, n(%)21 (50)21 (72)0 (0)&amp;lt;0.0001Abstract Figure.

Symptomatic Premature Ventricular Contractions in Vasovagal Syncope Patients: Autonomic Modulation and Catheter Ablation.

IntroductionThere has been limited reports about the comorbid premature ventricular contractions (PVCs) and vasovagal syncope (VVS). Deceleration capacity (DC) was demonstrated to be a quantitative evaluation to assess the cardiac vagal activity. This study sought to report the impact of autonomic modulation on symptomatic PVCs in VVS patients.Methods and ResultsTwenty-six VVS patients with symptomatic idiopathic PVCs were consecutively enrolled. Identification and catheter ablation of left atrial ganglionated plexi (GP) and PVCs were performed in 26 and 20 patients, respectively. Holter 24 h-electrocardiograms were performed before and after the procedure to evaluate DC and PVCs occurrence. Eighteen patients were subtyped as DC-dependent PVCs (D-PVCs) and eight as DC-independent PVCs groups (I-PVCs). In D-PVCs group, circadian rhythm of hourly PVCs was positively correlated with hourly DC (P < 0.05) while there was no correlation in I-PVCs group (P > 0.05). Fifty-three GPs with positive vagal response were successfully elicited (2.0 ± 0.8 per patient). PVCs failed to occur spontaneously nor to be induced in six patients. In the remaining 20 patients, PVCs foci identified were all located in the ventricular outflow tract region. Post-ablation DC decreased significantly from baseline (P < 0.05). During mean follow-up of 10.64 ± 6.84 months, syncope recurred in one patient and PVCs recurred in another. PVCs burden of the six patients in whom neither catheter ablation nor antiarrhythmic drugs were applied demonstrated a significant decrease during follow-up (P = 0.037).ConclusionAutonomic activities were involved in the occurrence of symptomatic idiopathic PVCs in some VVS patients. D-PVCs might be facilitated by increased vagal activities. Catheter ablation of GP and PVCs foci may be an effective, safe treatment in patients with concomitant VVS and idiopathic PVCs.

Substrate guided ablation of idiopathic right ventricular outflow tract premature ventricular contractions in patients with low arrhythmia burden during the procedure

Abstract Background Ablation of premature ventricular contractions (PVCs) is currently based on activation mapping. This strategy is impaired by the absence or paucity of PVCs on the day of the procedure. Frequently, isolated diastolic potentials (DP) are present at the successful ablation site in sinus rhythm (SR), although their meaning is still a matter of debate. Objective Evaluate the feasibility and results of a substrate-based approach for ablation of idiopathic right ventricular outflow tract (RVOT) PVCs, in patients that present with a low PVC burden during the procedure. Methods We included 12 consecutive patients referred for ablation of frequent (&amp;gt;10000/24 hours) idiopathic PVCs from the RVOT that present with less than 2 PVCs/min in the beginning of the procedure. The ablation was based on fast mapping of the RVOT in SR looking for DPs, defined as isolated small amplitude potentials occurring after the T wave of the surface ECG in SR (Figure). The area with DPs was marked and a reduced activation mapping of the PVCs was done in that area. We evaluated the procedure time, mapping, fluoroscopy and radiofrequency (RF) application times. The number of points used for the maps, the area of DPs, local activation time and success rate. Values are presented as median (Q1-Q3). Electroanatomical mapping of the RVOT in SR was also performed in a control group of 10 subjects that underwent ablation of supraventricular arrhythmias, to evaluate the prevalence of DPs in subjects without PVCs. Results The number of PVCs during the procedure was 1 (0.1–1.6)/min. Both groups did not differ in relation to age or gender. Median age 45 (34–65) years, 6 males in the PVC group and 40 (33–65) years, 6 males in the control group, p=0.821 and p=0.231 respectively. The number of points sampled per RVOT map in SR was 400 (193–500) in the PVC group and 330 (277–425) in the control group, p=0.539. All patients in the study group had DPs in the RVOT. None of the control group subjects had DPs in the RVOT. Ablation data is presented in the Table. The acute success rate was 100%. After a median follow-up time of 4 (3–6) months one patient had recurrence. Conclusion In these group of patients with very low PVC burden during the procedure, this approach partially based on substrate mapping, made ablation of the PVCs feasible, in a fast and efficient way. Funding Acknowledgement Type of funding source: None

Idiopathic Premature Ventricular Contractions From the Outflow Tract Display an Underlying Substrate That Can Be Unmasked by a Type 2 Brugada Electrocardiographic Pattern at High Right Precordial Leads.

Background: Patients with premature ventricular contractions (PVCs) from the right ventricular outflow tract (RVOT) and apparently normal hearts, can have ST elevation similar to type 2 or type 3 Brugada pattern in the electrocardiographic (ECG) performed at a higher position. Cardiac magnetic resonance (CMR), has shown conflicting data regarding existence of structural abnormalities in patients with idiopathic PVCs from the RVOT.Objective: Our aim was to evaluate the prevalence of low voltage areas (LVAs) in the RVOT of patients with PVCS from the outflow tract, and in a control group. Secondly, assess for the presence of a non-invasive ECG marker.Methods: A 56 consecutive patients, 45 with frequent PVCs (>10000/24 h) LBBB, vertical axis, negative in aVL and 11 subjects without PVCs. Arrhythmogenic right ventricular cardiomyopathy was ruled out in all patients. An ECG was performed with V1–V2 at the level of the second intercostal space and the presence of ST-segment elevation with a Type 2 or 3 Brugada pattern (Type 2 BrP) was assessed. Bipolar voltage map of the RVOT was performed in sinus rhythm (0.5–1.5 mV color display). Areas with electrograms <1.5 mV represented the LVA. The area adjacent to the pulmonary valve usually displays voltage between 0.5 and 1.5 mV and is classified as transitional-voltage zone. Presence of LVAs outside this transitional-voltage zone were estimated. We compared two groups with and without ST-segment elevation and tested for the association between ECG pattern and LVAs.Results: None of the patients in the control group had ST-segment elevation or LVAs. In the PVC group, no patient had type 1 Brugada pattern, 29 patients (64%) had type 2 or 3 ST-segment elevation (Type 2 BrP), and 28 (62%) had LVAs outside the transitional-voltage zone. LVAs were more frequent in patients with Type 2 BrP; 93% versus 4%, p < 0.0001. The ECG pattern was associated with the presence of LVAs, OR (95% CI): 202.50 (16.92–2423), p < 0.0001.Conclusion: Low voltage areas were frequently present in the RVOT of patients with idiopathic PVCs. They were absent in controls and can be unmasked by the presence of Type 2 BrP in high right precordial leads.