Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge.

BACKGROUND: The significance of autonomic dysfunction in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVE: Utilizing a novel "dual stressor" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model. METHODS: In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling. RESULTS: Exercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload. CONCLUSIONS: Sympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.

Arrhythmia-Induced Cardiomyopathy: JACC State-of-the-Art Review.

Arrhythmias frequently accompany heart failure and left ventricular dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions can induce a reversible form of dilated cardiomyopathy (CM) known as arrhythmia-induced CM (AiCM). The intriguing question is why certain individuals are more susceptible to AiCM, despite similar arrhythmia burdens. The primary challenge is determining the extent of arrhythmias' contribution to left ventricular systolic dysfunction. AiCM should be considered in patients with a mean heart rate of >100 beats/min, atrial fibrillation, or a PVC burden of >10%. Confirmation of AiCM occurs when CM reverses upon eliminating the responsible arrhythmia. Therapy choice depends on the specific arrhythmia, patient comorbidities, and preferences. After left ventricular function is restored, ongoing follow-up is essential if an abnormal myocardial substrate persists. Accurate diagnosis and treatment of AiCM have the potential to enhance patients' quality of life, improve clinical outcomes, and reduce hospital admissions and overall health care costs.

Left ventricular remodeling in premature ventricular contraction-induced cardiomyopathy: Effect of coupling intervals and atrioventricular dissociation.

Background: Left ventricular dyssynchrony (LVD) and postextrasystolic potentiation (PESP) associated with premature ventricular contractions (PVCs) may play a role in the development of premature ventricular contraction-induced cardiomyopathy (PVC-CM). Long-coupled (LC) PVCs have a greater LVD than short-coupled (SC) PVCs, whereas SC-PVCs have a stronger PESP than LC-PVCs. Objective: The purpose of this study was to compare SC-PVCs and LC-PVCs to evaluate the roles of LVD, PESP, and atrioventricular dissociation (AVD) in the development of PVC-CM. Methods: Thirty-six canines underwent pacemaker implantation to induce bigeminal right ventricular apical epicardial PVCs (50% burden) for 12 weeks. Telemetry assessed PVC burden and AVD. Animals were grouped as SC-PVC (coupling interval [CI] 200-220ms), LC-PVC (CI 330 ms), or sham (control). Echocardiographic changes, AVD, and hemodynamics were monitored for 12 weeks. Results: PVC burden was similar between SC-PVC and LC-PVC groups but was statistically higher in the SC-PVC group (50% vs 47.5%; P = .028). After 12 weeks, left ventricular ejection fraction (LVEF) significantly decreased in both SC-PVC and LC-PVC groups (47.1% ± 1.4% and 45.5% ± 2%, respectively) compared to sham group (61% ± 1.6%; P <.001). Overall AVD was similar between SC-PVC and LC-PVC groups, and there was no significant correlation between AVD and reduction in LVEF at 12 weeks (r = 0.09, P = .5; and r = 0.06, P = .8, respectively). Additionally, both SC-PVC and LC-PVC groups experienced substantial declines in max and min dP/dt after 12 weeks compared to baseline. Conclusion: Neither PVC CI nor AVD played an independent role in the development or severity of PVC-CM. LVD and PESP make equal relative contributions to the development of PVC-CM.

Mechanisms of adaptive hypertrophic cardiac remodeling in a large animal model of premature ventricular contraction-induced cardiomyopathy.

Frequent premature ventricular contractions (PVCs) promoted eccentric cardiac hypertrophy and reduced ejection fraction (EF) in a large animal model of PVC-induced cardiomyopathy (PVC-CM), but the molecular mechanisms and markers of this hypertrophic remodeling remain unexplored. Healthy mongrel canines were implanted with pacemakers to deliver bigeminal PVCs (50% burden with 200-220 ms coupling interval). After 12 weeks, left ventricular (LV) free wall samples were studied from PVC-CM and Sham groups. In addition to reduced LV ejection fraction (LVEF), the PVC-CM group showed larger cardiac myocytes without evident ultrastructural alterations compared to the Sham group. Biochemical markers of pathological hypertrophy, such as store-operated Ca2+ entry, calcineurin/NFAT pathway, ß-myosin heavy chain, and skeletal type α-actin were unaltered in the PVC-CM group. In contrast, pro-hypertrophic and antiapoptotic pathways including ERK1/2 and AKT/mTOR were activated and/or overexpressed in the PVC-CM group, which appeared counterbalanced by an overexpression of protein phosphatase 1 and a borderline elevation of the anti-hypertrophic factor atrial natriuretic peptide. Moreover, the potent angiogenic and pro-hypertrophic factor VEGF-A and its receptor VEGFR2 were significantly elevated in the PVC-CM group. In conclusion, a molecular program is in place to keep this structural remodeling associated with frequent PVCs as an adaptive pathological hypertrophy.

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 12 weeks), SR-Ca2+ reuptake was investigated by measuring Ca2+ dynamics and analyzing protein expression. Kinetic analysis of Ca2+ reuptake in electrically paced myocytes showed a ~ 21 ms 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 ~ 22 ms 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.

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

Background: Strain 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 results: Pacemakers 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. Conclusion: Our 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.

Eccentric hypertrophy in an animal model of mid- and long-term premature ventricular contraction-induced cardiomyopathy.

BACKGROUND: Tachycardia and heart rate irregularity are proposed triggers of premature ventricular contraction-induced cardiomyopathy (PVC-cardiomyopathy). Bigeminal premature atrial and ventricular contractions (PACs and PVCs) increase heart rate and result in rhythm irregularities but differ in their effects on ventricular synchrony. Comparing chronic bigeminal PACs with PVCs would provide insights into mechanisms of PVC-cardiomyopathy. OBJECTIVE: To compare the impact of chronic PACs and PVCs on ventricular hemodynamics, structure, and function. METHODS: Pacemakers were implanted in 27 canines to reproduce atrial (PACs, n = 7) or ventricular bigeminy (PVCs, n = 11) for 12 weeks, and compared to sham-operated animals (n = 9). Four additional animals were exposed to long-term bigeminal PVCs (48 weeks). Hemodynamic changes were assessed using a pressure-transducing catheter at baseline and 12 weeks. Cardiac remodeling was monitored by transthoracic echocardiography throughout the 12- and 48-week protocols in the respective groups. RESULTS: PVC group demonstrated a significant decrease in left ventricular (LV) ejection fraction and contractility (max dP/dt), impaired LV lusitropy (min dP/dt), and increase in LV dimensions and LV mass at 12 weeks without further deterioration beyond 16 weeks. Despite increased LV mass, relative wall thickness decreased, consistent with eccentric hypertrophy. No significant cardiac remodeling was noted in either sham or PAC groups at 12 weeks. CONCLUSION: In contrast to bigeminal PACs, PVCs result in a cardiomyopathy characterized by reduced LV ejection fraction, LV dilation, and eccentric hypertrophy that plateaus between 12 and 16 weeks. The lack of remodeling in chronic PACs suggests that tachycardia and heart rate irregularity do not play a significant role on the development of PVC-cardiomyopathy.

Clinical and translational insights on premature ventricular contractions and PVC-induced cardiomyopathy.

The medical community's understanding of the consequences of premature ventricular contractions (PVCs) and PVC-induced cardiomyopathy has been derived mostly from observational and large population-based studies. Due to the difficulty of predicting the development of PVC-cardiomyopathy, the acute and chronic cardiac effects of PVCs and the mechanism of PVC-cardiomyopathy have been derived from pre-clinical studies with large animal models. Recently, these studies have described myocardial substrates that could potentially increase morbidity and mortality in patients with frequent PVCs and PVC-cardiomyopathy. In this paper, we provide an up-to-date comprehensive review of these pre-clinical and clinical studies.

Outcomes of Premature Ventricular Contraction-Cardiomyopathy in the Veteran Population: A Secondary Analysis of the CHF-STAT Study.

OBJECTIVES: This study sought to assess the rate and outcomes of premature ventricular contractions (PVC)-cardiomyopathy from the CHF-STAT (Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure) trial, a population with cardiomyopathy (left ventricular [LV] ejection fraction of <40%) and frequent PVCs (>10 PVCs per hour). BACKGROUND: PVCs are associated with heart failure and PVC-cardiomyopathy. The prevalence of PVC-cardiomyopathy and outcome benefits of PVC suppression are not clear. METHODS: A secondary analysis of the CHF-STAT study was performed to compare the rate of successful PVC suppression (≥80% PVC reduction), LV recovery (defined as improvement in LV ejection fraction of ≥10% points), and PVC-cardiomyopathy between amiodarone and placebo groups at 6 months. PVC-cardiomyopathy was defined if both PVC reduction of ≥80% and LV ejection fraction improvement of ≥10% were present at 6 months. Cardiac events (death or resuscitated cardiac arrest) were compared between PVC-cardiomyopathy versus non-PVC-cardiomyopathy during a 5-year follow-up. RESULTS: The rates of successful PVC suppression and LV recovery were significantly higher in the amiodarone (72% and 39%, respectively) when compared to the placebo group (12% and 16%, respectively; p < 0.001), regardless of cardiomyopathy etiology. PVC-cardiomyopathy was present in 29% and 1.8% of patients in the amiodarone and placebo groups, respectively (p < 0.001). Similar PVC-cardiomyopathy rates were found in ischemic (24% amiodarone vs. 2% placebo; p < 0.001) and nonischemic populations (41% amiodarone vs. 1.5% placebo; p < 0.001). Death and resuscitated cardiac arrest were significantly lower in patients with PVC-cardiomyopathy and those treated with amiodarone. CONCLUSIONS: The overall prevalence of PVC-cardiomyopathy in the CHF-STAT study was significant regardless of ischemic substrate (29%, overall population; 41%, nonischemic cardiomyopathy). Treatment of PVC-cardiomyopathy with amiodarone is likely to improve survival in this high-risk population.

Intermediate-term performance and safety of His-bundle pacing leads: A single-center experience.

BACKGROUND: The short-term safety, feasibility, and performance of His-bundle pacing (HBP) leads have been reported; however, their longer-term performance beyond 1 year remains unclear. OBJECTIVE: The purpose of this study was to examine the intermediate-term performance and safety of HBP. METHODS: All HBP lead implants at Virginia Commonwealth University between January 2014 and January 2019 were analyzed. HBP was performed using a Medtronic SelectSecure 3830-69 cm pacing lead. RESULTS: Of 295 attempts, successful HBP implantation (selective or nonselective) was seen in 274 cases (93%). Mean follow-up duration was 22.8 ± 19.5 months (median 19.5; interquartile range 11-33). Mean age was 69 ± 15 years; 58% were males; and ejection fraction <50% was noted in 30%. Indications for pacemaker included sick sinus syndrome in 41%, atrioventricular block in 36%, cardiac resynchronization therapy in 7%, and refractory atrial fibrillation in 15%. Selective HBP was achieved in 33%. Mean HBP capture threshold at implant was 1.1 ± 0.9 V at 0.8 ± 0.2 ms, which significantly increased at chronic follow-up to 1.7 ± 1.1 V at 0.8 ± 0.3 ms (P <.001). Threshold was ≥2.5 V in 24% of patients, and 28% had an increase in HBP threshold ≥1 V. Loss of His-bundle capture at follow-up (septal right ventricular pacing) was seen in 17%. There was a total of 31 (11%) lead revisions, primarily for unacceptably high thresholds. CONCLUSION: Although HBP can prevent or improve pacing-induced cardiomyopathy, the elevated capture thresholds, loss of His-bundle capture, and lead revision rates at intermediate follow-up are of concern. Longer-term follow-up data from multiple centers are needed.

Differences in heart rate among recent marijuana use groups.

BACKGROUND: Marijuana use increases cardiac sympathetic activity within minutes of its use and this effect may begin to decrease as soon as one hour after marijuana use. However, the cardiovascular effects of marijuana use more than an hour after use is poorly characterized. The purpose of the current study is to compare heart rate, a marker of cardiac sympathetic activity, across recent marijuana use groups (never used: N.=63; recent use [in the past 24 hours; subacute] N.=13; in the past 7 days, but not in the past 24 hours: N.=17). Overall, the current sample included 93 African American/Black college students, with a mean age of 20.03±2.21 years. METHODS: Participants completed a demographic form, a brief battery of psychological questionnaires, and had their heart rate assessed at baseline. RESULTS: Analysis of covariance showed that heart rate was statistically significantly lower in the recent use group (62.38 bpm) compared with the non-users group (73.92 bpm). This difference persisted before and after statistically adjusting for demographic covariates. CONCLUSIONS: These results suggest that there may be a cardiovascular process that occurs when using marijuana that results in a compensatory, reduced heart rate.

Inverse associations between parasympathetic activity and cognitive flexibility in African Americans: Preliminary findings.

Previous research suggests that vagal activity and executive function (EF) are positively associated. However, existing data exploring the relationship between HRV and EF remains limited. Though Blacks may have higher HRV, they remain underrepresented in previous research examining HRV and EF. The current study aimed to determine the relationship between EF and HRV in a sample of 92 Black undergraduates (Mean age = 20.32, SD = 2.28). Participants wore an 6­lead ambulatory electrocardiographic impedance monitoring system to obtain the root mean square of interbeat interval differences (rMSSD) and Cardiac Sympathetic Index. After baseline autonomic activity assessment, participants completed the Berg Card Sorting Test. Utilizing hierarchical regression analyses, HRV was negatively associated with correct responses (Beta = -0.40, SE = 0.04, p=0.01) and categories experienced (Beta = -0.37, SE = 0.01, p=0.01), and positively associated with total errors (Beta = 0.39, SE =0.04, p=0.01). To further elucidate these findings, participants were assigned to coinhibition (n = 12), parasympathetically dominant (n = 34), sympathetically dominant (n = 35), or coactivation (n = 11) autonomic space subgroups. Participants in the sympathetically dominant subgroup completed more categories (M = 6.86, SD = 2.13) and committed fewer errors (M = 30.63, SD = 11.53) than their parasympathetic counterparts (M = 5.74, SD = 2.44; M = 43.29, SD = 18.83, respectively). This study suggests that a state of sympathetic arousal immediately prior to the administration of an EF task, may aid in better task performance.

Proarrhythmic effect of automatic threshold testing algorithm in dual chamber devices.

BACKGROUND: Operation of auto-threshold testing (ATT) algorithm in current dual chamber cardiac devices require temporary shortening of atrio-ventricular (AV) delay to accurately measure evoked potential (capture) after a pacing pulse. Near simultaneous AV pacing causes atrial pressure elevation and may be associated with atrial arrhythmias. OBJECTIVE: We evaluated the prevalence of atrial arrhythmias induced by ATT in Abbott devices. METHODS: Device clinic records were reviewed at a single center for patients with dual chamber Abbott pacemaker/ICD. ATT-induced atrial fibrillation (AF) cases were defined as new appropriate mode switch episodes while the ATT was operating. The auto-capture test trends were defined as unstable if there were deviations >1 V in capture threshold trend events that did not correlate with routine in-office testing. RESULTS: One hundred and seventy patients were programmed in dual chamber pacing mode. The ventricular ATT was active in 118 patients and of these 78 had true mode switch episodes. Six patients developed AF during ventricular ATT. Three patients had most recorded atrial arrhythmias in close association with ATT (63%, 66%, 100% vs 2%,9%, 33% in other patients with known prior AF). An unstable auto-capture trend curve was seen in 33 patients (6 showing ATT-induced AF) versus 85 patients with stable auto-capture curve and no ATT-induced AF (P = .0001, the χ2 test). CONCLUSION: Ventricular auto-capture algorithm use is associated with induction of AF in dual chamber Abbott devices with a prevalence of over 5%. AF occur more frequently (18%) in patients with erratic ventricular ATT trend results.

Post-extrasystolic potentiation as a predictor of premature ventricular contraction-cardiomyopathy in an animal model.

AIMS: High premature ventricular contractions (PVCs) burden does not always predict the development of PVC-cardiomyopathy (CM). We sought to evaluate post-extrasystolic potentiation (PESP) of left ventricular ejection fraction (LVEF) to predict the severity of PVC-CM in an animal model. METHODS AND RESULTS: Right ventricular apical bigeminal PVCs were introduced for 12 weeks in 11 canines to induce PVC-CM. Echocardiograms were performed to obtain LVEF without ectopy (Echo-1) and during PVCs (200 and 350 ms coupling intervals, Echo-2, and Echo-3, respectively), and premature atrial contractions (PACs) (Echo-4) at baseline and after 12 weeks of bigeminal PVCs. PESP was calculated as delta-LVEF between the sinus beat post-ectopy LVEF (Echo-2, -3, and -4, respectively) and LVEF without PVC (Echo-1) at baseline and 12 weeks of high PVC burden. A hyperdynamic LV function (LVEF > 70%) was noted in all animals only with early-coupled PVCs (LVEF at 200 ms: 74.4 ± 6%) at baseline. While PVC PESP at 200 ms had a strong significant correlation with the final 12-week LVEF (R = 0.8, P = 0.003), PVC PESP at 350 ms and PAC PESP had a positive but non-significant correlation (R = 0.53, P = 0.09, and R = 0.29, P = 0.34, respectively). Premature ventricular contraction PESP at 350 ms was significantly higher after PVC-CM had developed (delta-LVEF baseline 2.7 ± 2.9% vs. 12 weeks 18.6 ± 12.3% P < 0.001). CONCLUSION: Bigeminal early-coupled PVCs cause hyperdynamic left ventricular function in the structurally normal canine heart due to PESP. The degree of PESP at baseline is inversely proportional to the PVC-CM severity at 12 weeks and maybe a predictor of PVC-CM as it may assess the myocardial adaptation reserve to PVCs.

Persistent Proarrhythmic Neural Remodeling Despite Recovery From Premature Ventricular Contraction-Induced Cardiomyopathy.

BACKGROUND: The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVES: This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM. METHODS: In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure. Bigeminal PVCs (200 ms coupling) were applied for 12 weeks to induce PVC-CM in 7 animals then disabled for 4 weeks to allow complete recovery of left ventricular ejection fraction (LVEF), versus 5 sham controls. RESULTS: After 12 weeks of PVCs, LVEF (p = 0.006) and dP/dT (p = 0.007) decreased. Resting SNA (p = 0.002) and VNA (p = 0.04), exercise SNA (p = 0.01), SNA response to evoked PVCs (p = 0.005), heart rate (HR) at rest (p = 0.003), and exercise (p < 0.04) increased, whereas HR variability (HRV) decreased (p = 0.009). There was increased spontaneous atrial (p = 0.02) and ventricular arrhythmias (p = 0.03) in PVC-CM. Increased SNA preceded both atrial (p = 0.0003) and ventricular (p = 0.009) arrhythmia onset. Clonidine suppressed SNA and abolished all arrhythmias. After disabling PVC for 4 weeks, LVEF (p = 0.01), dP/dT (p = 0.047), and resting VNA (p = 0.03) recovered to baseline levels. However, SNA, resting HR, HRV, and atrial (p = 0.03) and ventricular (p = 0.03) proarrhythmia persisted. There was sympathetic hyperinnervation in stellate ganglia (p = 0.02) but not ventricles (p = 0.2) of PVC-CM and recovered animals versus sham controls. CONCLUSIONS: Neural remodeling in PVC-CM is characterized by extracardiac sympathetic hyperinnervation and sympathetic neural hyperactivity that persists despite normalization of LVEF. The altered cardiac sympathovagal balance is an important trigger and substrate for atrial and ventricular proarrhythmia.

Fluoroscopy reduction during device implantation by using three-dimensional navigation. A single-center experience.

BACKGROUND AND OBJECTIVES: The use of nonfluoroscopic three-dimensional electroanatomic mapping (3DM) systems reduces radiation exposure during ablation procedures. In this study, we sought to determine the value of 3DM during routine device implant procedures. METHODS: Seventy nonselected patients underwent implantation of a single chamber, dual chamber, or biventricular device guided by Ensite (Abbott Laboratories) to limit fluoroscopy use and compared with 70 consecutive patients, who underwent matching procedures with standard fluoroscopy use (FL) in the period immediately preceding the use of 3DM. The venous anatomy, right atrium, and ventricle and coronary sinus were mapped with 0.035 inch J-wire, quadripolar catheter, and/or angioplasty wire. The leads were advanced under real-time visualization in Ensite. RESULTS: 3DM reduced both fluoroscopy time and dose. Median fluoroscopy time for FL vs 3DM was 5.5 minutes (interquartile range [IQR]: 3.8-8.1) vs 0.9 minutes (IQR: 0.6-1.9) (P < .001) for single chamber devices, 6.3 minutes (IQR: 5.1-7.9) vs 3.3 minutes (IQR: 1.9-4) (P < .001) for dual-chamber devices, and 28.6 minutes (IQR: 19.6-36.2) to 14.7 minutes (IQR: 10.4-22.3) (P = .009) for biventricular devices, respectively. The median air kerma for FL vs 3DM was 15.4 mGy (IQR: 8.1-30.2) vs 4 mGy (IQR: 1.8-8) (P < .001) for single chamber devices, 16 mGy (IQR: 12-18.5) to 9.4 mGy (IQR: 7.5-11.3) (P = .001) for dual-chamber devices, and 324 mGy (IQR: 143-668.7) to 115 mGy (IQR:77-204) (P = .014) for biventricular devices, respectively. There were no procedural complications. At 3-month follow-up, there was no difference in voltage threshold measurements between the groups. CONCLUSION: The use of 3DM leads to significantly reduced fluoroscopy time and fluoroscopy dose during routine device implantation.

Consequences of chronic frequent premature atrial contractions: Association with cardiac arrhythmias and cardiac structural changes.

INTRODUCTION: Frequent premature ventricular contractions (PVCs) can cause cardiomyopathy (CM). Postextrasystolic potentiation (PESP) and irregularity have been in implicated as triggers of PVC-CM. Because both phenomena can also be found in premature atrial contractions (PACs), it is speculated that frequent PACs have similar consequences. METHODS AND RESULTS: A single-center, retrospective study included all consecutive patients undergoing a 14-day Holter monitors (November 2014 to October 2016). Patients were divided into four groups by ectopy burden group 1 (<1%) and remaining by tertiles (group 2-4). Echocardiographic and arrhythmic data were compared between PAC and PVC burdens. In addition, a translational PAC animal model was used to assess the chronic effects of frequent PACs. A total 846 patients were reviewed. In contrast to PVCs, we found no difference in left ventricular ejection fraction (LVEF), end-systolic and end-diastolic dimensions and presence of CM (LVEF <50%) between different PAC groups. Multivariate regression analysis demonstrated that only PVC burden predicted low EF (odds ratio, 1.1; confidence interval, 1.03-1.13; P = .001). While there was a weak correlation between PAC burden and supraventricular tachycardia (SVT) episodes and atrial fibrillation (AF) burden (r = 0.19; P < .001), there was no correlation between PAC burden and LVEF or CM. Finally, atrial bigeminy in our animal model did not significantly decrease LVEF after 3 months. CONCLUSION: PAC burden is associated with increased AF and SVT episodes. In contrast to a high PVC burden, a high PAC burden is not associated with CM. Our findings suggest that heart rate irregularity and/or PESP may play a minimal role in the pathophysiology of PVC-CM.