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Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF.The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events.CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events.In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.

Purpose. Amiodarone is a source of excess iodine that may induce thyroid dysfunction. The aim of the present analysis was to evaluate the magnitude and time course of 24-hr urinary iodine excretion and its potential relationship with thyroid disorders in patients on antiarrhythmic prophylaxis with amiodarone. Methods. 24-hr urinary iodine excretion and thyroid function were evaluated in 67 patients on chronic amiodarone therapy. All patients were clinically and biochemically euthyroid before starting treatment and were followed up by 6-month measurements of 24-hr urinary iodine excretion and plasma TSH levels. Results. Since amiodarone initiation, 20 patients developed thyroid dysfunction (14 hypothyroidism, 3 subclinical hypothyroidism, 3 hyperthyroidism). No differences were observed in terms of treatment length or urinary iodine levels between patients remaining euthyroid and those developing thyroid dysfunction: urinary iodine in the euthyroid group was 8094 µg/24h (IQR 4082-10766) vs 10851 µg/24h (IQR 8529-12804) in the thyroid dysfunction group at 6 months (p = 0.176) and 8651 µg/24h (IQR 6924-11574) vs 8551 µg/24h([IQR 4916-13580) (p = 0.886) at one year from amiodarone initiation. The occurrence of thyroid dysfunction was equally distributed among patients taking amiodarone for more than one year versus those under treatment for less than one year. Upon amiodarone withdrawal, normal range of urinary iodine was achieved after a mean time of 15.2 ± 7.7 months. Conclusion. These results suggest no correlation between 24-hr urinary iodine excretion and thyroid dysfunction in patients on amiodarone therapy. Thyroid disorders following amiodarone administration likely depend on the individual predisposition to iodine load.

Background Ventricular arrhythmias (VAs) have never been systematically investigated in patients with myocarditis at different stages. Objectives The purpose of this study was to compare baseline and follow-up characteristics of VAs in patients with active myocarditis (AM) versus previous myocarditis (PM). Methods A total of 185 consecutive patients (69% males, age 44 ± 15 years, left ventricular ejection fraction 49 ± 14%) with myocarditis and VA at index hospitalization, including ventricular fibrillation, ventricular tachycardia (VT), nonsustained ventricular tachycardia (NSVT), and Lown’s grade ≥2 premature ventricular complexes, were enrolled. AM and PM groups were defined based on endomyocardial biopsy and cardiac magnetic resonance findings. A subset of patients (n = 46, 25%) also underwent electroanatomic mapping and VA transcatheter ablation. Results At presentation, AM patients (n = 123, 66%) more commonly had ventricular fibrillation (8 cases vs. 0 cases; p = 0.053), and both irregular (61% vs. 11%; p Conclusions In myocarditis patients, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis.

Background: Ventricular arrhythmias (VAs) are rare in pediatric patients, especially in absence of structural heart disease (SHD). Few data are available regarding the invasive VAs treatment with catheter ablation (CA) in pediatric patients and predictors of outcomes have not been fully investigated. Objective: To describe the clinical presentation, procedural characteristics, and outcomes in pediatric patients undergoing CA for VAs. Methods: Eighty-one consecutive pediatric patients (58 male [72%], 15.5 ± 2.2 years) treated by CA for ventricular tachycardia (VT) or premature ventricular beats (PVBs) were retrospectively evaluated. Study endpoints were VAs recurrence and mortality for any cause. Results: Ninety-five procedures were performed in 81 patients, 52 (55%) PVBs and 43 (45%) VT ablations. During a follow-up of 35.0 months (interquartile range = 13.0–71.0), 14 patients (14.7%) had a VA recurrence: 11 (33.3%) patients treated with CA for VT and 3 (6.2%) patients treated for PVBs (p

Background Effects of immunosuppressive therapy (IST) on ventricular arrhythmias (VA) have not been reported in immune-mediated biopsy-proven myocarditis patients. Furthermore, myocarditis arrhythmic risk is still unpredictable. The aim of our study was to evaluate effectiveness of IST on VA in myocarditis patients, and stratify their arrhythmic risk, using clinical and diagnostic features, including serum organ-specific anti-heart (AHA) and antiintercalated-disk autoantibodies (AIDA). Methods From a cohort of 498 consecutive patients, we enrolled 255 cases with biopsy-proven virus-negative myocarditis and evidence of VA (VF, VT, NSVT, and Lown's grade ≥2 PVC) at index hospitalization. Serum AHA and AIDA were detected by a standardised indirect immunofluorescence technique. Whenever accepted and non-contraindicated, IST was started. Controls (IST-) were chosen after 1:1 matching to IST+ cases by age, gender, ethnicity, left ventricular ejection fraction, VA type, and treatment. Prospective follow-up (FU), occurred at defined timepoints. Results 58 matched patient couples (42±13 y, 67% males, 50% IST+) were analyzed in the main study cohort. Overall, 28 (24%) had VT, and 62 (53%) were discharged with ICD. IST duration was 12±1 months. No patients died and no serious complications from IST occurred. By 24-month FU, major VA occurred in 6 IST+ vs. 10 IST- patients (p=0.420), with no cases of VT following IST termination. As compared to IST- ones, IST+ patients showed a significant reduction in NSVT and PVC burden, as well as an improvement in clinical, laboratory and imaging findings (all p Conclusions In immune-mediated virus-negative myocarditis patients presenting with VA, IST is feasible and effective on NSVT and PVC burden, as well as on structural, laboratory and imaging endpoints. Short-term effects are limited on major VA, which were independently associated with major arrhythmic onset and positive AIDA, in keeping with the proposed etiopathogenetic involvement of autoimmunity in virus-negative myocarditis. Funding Acknowledgement Type of funding source: None

Supplemental Digital Content is available in the text., Background: The development of multielectrode mapping catheters has expanded the spectrum of mappable ventricular tachycardias (VTs). Full diastolic pathway recording has been associated with a high rate of VT termination during radiofrequency ablation as well as noninducibility at study end. However, the role of diastolic pathway mapping on VT recurrence has yet to be clearly elucidated. We aimed to explore the role of complete diastolic pathway activation mapping on VT recurrence. Methods: Eighty-five consecutive patients who underwent VT ablation guided by high-density mapping were enrolled. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway, or no diastolic pathway map performed. Recurrences of VT were defined as appropriate implantable cardioverter defibrillator therapies or on the basis of ECG-documented arrhythmia. Results: Eighty-five patients were included. Complete recording of the diastolic pathway was achieved in 36/85 (42.4%) patients. Partial recording of the diastolic pathway of the clinical VT was achieved in 24/85 (28.2%) patients. No recording of the diastolic pathway of the clinical VT was feasible in 25/85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrence was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88%, 50%, and 55% in patients who had full diastolic activity recorded, partial diastolic activity recorded, or underwent substrate modification, respectively; the observed differences were statistically significant (P=0.02). Conclusions: Mapping of the entire diastolic pathway was associated with a higher freedom from VT recurrence as compared with partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies.

Background: In patients with an ischemic cardiomyopathy (ICM), the combination of late potential (LP) abolition and postprocedural ventricular tachycardia (VT) noninducibility is known to be the desirable end point for a successful long-term outcome after VT ablation. We investigated whether LP abolition and VT noninducibilty have a similar impact on the outcomes of patients with non-ICMs (NICM) undergoing VT ablation. Methods: A total of 403 patients with NICM (523 procedures) who underwent a VT ablation from 2010 to 2016 were included. The procedure end points were the LP abolition (if the LPs were absent, other ablation strategies were undertaken) and the VT noninducibilty. Results: The underlying structural heart disease consisted of dilated cardiomyopathy (DCM, 49%), arrhythmogenic right ventricular dysplasia (ARVD, 17%), postmyocarditis (14%), valvular heart disease (8%), congenital heart disease (2%), hypertrophic cardiomyopathy (2%), and others (5%). The epicardial access was performed in 57% of the patients. At baseline, the LPs were present in 60% of the patients and a VT was either inducible or sustained/incessant in 85% of the cases. At the end of the procedure, the LP abolition was achieved in 79% of the cases and VT noninducibility in 80%. After a multivariable analysis, the combination of LP abolition and VT noninducibilty was independently associated with free survival from VT (hazard ratio, 0.45 [95% CI, 0.29–0.69], P =0.0002) and cardiac death (hazard ratio, 0.38 [95% CI, 0.18–0.74], P =0.005). The benefit of the LP abolition on preventing the VT recurrence in patients with ARVD and postmyocarditis appeared superior to that observed for those with DCM. Conclusions: In patients with NICM undergoing VT ablation, the strategy of LP abolition and VT noninducibilty were associated with better outcomes in terms of long-term VT recurrences and cardiac survival. Graphic Abstract: A graphic abstract is available for this article.

Objectives: This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis. Background: The effects of immunosuppressive therapy (IST) on ventricular arrhythmia (VA) have not been reported in patients with immune-mediated biopsy-proven myocarditis. Furthermore, myocarditis arrhythmic risk is still unpredictable. Methods: We enrolled 255 patients with biopsy-proven virus-negative myocarditis and VA (major: ventricular fibrillation, ventricular tachycardia; minor: nonsustained ventricular tachycardia, Lown grade ≥2 premature ventral complexes) at presentation. Serum cardiac autoantibodies (antiheart antibodies, anti–intercalated disk autoantibodies [AIDA]) were detected by a standardized indirect immunofluorescence technique. Whenever accepted and noncontraindicated, IST was started. Control individuals (IST−) were chosen after 1:1 matching to IST+ patients by age, sex, ethnicity, left ventricular ejection fraction, VA type, and treatment. Results: A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1 months. By the 24-month prospective follow-up, major VA occurred in 6 IST+ versus 10 IST− patients (p = 0.42), with no episodes following IST termination. As compared to IST− patients, IST+ patients showed a significant reduction in minor VA burden, as well as improvement in clinical, laboratory, and imaging findings (all p < 0.05). Major VA onset and positive AIDA status were independently associated with major VA at follow-up (hazard ratio [HR]: 14.2; 95% confidence interval [CI]: 2.9 to 68.7 and HR: 8.0; 95% CI: 2.6 to 25.2, respectively; both p < 0.001). Furthermore, in the whole study population (N = 255), IST was independently associated with protection from major VA (HR: 0.3; 95% CI: 0.2 to 0.7; p = 0.01) at 38 ± 21 months of follow-up. Conclusions: In patients with immune-mediated virus-negative myocarditis presenting with VA, IST is associated with positive effects on minor VA and nonarrhythmic endpoints. Short-term effects are limited on major VA, which were independently associated with major VA onset and positive AIDA.

The aim of this study was to characterize, during sinus rhythm, the electric activation abnormalities in post-myocardial infarction patients undergoing ablation of ventricular tachycardia (VT) in order to identify specific signatures of those abnormal electrograms (EGMs).In the setting of VT ablation, substrate characterization hinges on the identification of local abnormal ventricular activity (LAVA) and late potentials (LPs) that are considered to be related to the VT circuit.Patients scheduled for VT ablation underwent high-density ventricular substrate mapping. The substrate map during sinus rhythm was then compared with the activation maps of the clinical VT. Abnormal EGMs (LAVA and LPs) during sinus rhythm were characterized according to their configuration, duration, and amplitude and distinguished as belonging to bystander region or to the re-entrant circuit. Underlying electrophysiological mechanisms (wave-front collision, slow conduction) were identified on the activation maps and assigned to corresponding EGMs.Ten patients satisfied the criteria to be enrolled in the study. A mean of 5 ± 1 slow-conduction areas and 4 ± 2 wave-front collisions were identified. LAVA was due to slow conduction in 60.5%, followed by wave-front collision (17.5%). LPs were caused by slow conduction in 52% of cases and by wave-front collision in 43% of cases. During sinus rhythm, entrance and exit sites were characterized by LAVA, while at the VT isthmus, only LPs were identified. Cutoff values of duration 24.5 ms (95% sensitivity and 99% specificity) and amplitude 0.14 mV (90% sensitivity and 48.1% specificity) discriminated those LPs belonging to the circuit from those playing a bystander role.In the setting of post-myocardial infarction cardiomyopathy, specific EGM signatures are expressions of distinct electrophysiological phenomena. LAVA and LPs may play a bystander or an active role in the VT circuit, but only LPs with low amplitude and short duration predicted the VT isthmus.

Ventricular arrhythmias (VAs) have never been systematically investigated in patients with myocarditis at different stages.The purpose of this study was to compare baseline and follow-up characteristics of VAs in patients with active myocarditis (AM) versus previous myocarditis (PM).A total of 185 consecutive patients (69% males, age 44 ± 15 years, left ventricular ejection fraction 49 ± 14%) with myocarditis and VA at index hospitalization, including ventricular fibrillation, ventricular tachycardia (VT), nonsustained ventricular tachycardia (NSVT), and Lown's grade ≥2 premature ventricular complexes, were enrolled. AM and PM groups were defined based on endomyocardial biopsy and cardiac magnetic resonance findings. A subset of patients (n = 46, 25%) also underwent electroanatomic mapping and VA transcatheter ablation.At presentation, AM patients (n = 123, 66%) more commonly had ventricular fibrillation (8 cases vs. 0 cases; p = 0.053), and both irregular (61% vs. 11%; p 0.001) and polymorphic VA (NSVT and VT: 19% vs. 2%; p = 0.002; premature ventricular complexes: 63% vs. 16%; p 0.001). Only in PM patients with NSVT or VT, the dominant morphology (right-bundle branch block with superior axis) was 100% predictive of abnormal LV inferoposterior substrate at both cardiac magnetic resonance and electroanatomic mapping. At 27 ± 7 months prospective follow-up, 55 patients (30%) experienced malignant VA (AM vs. PM, p = 0.385). Although a prevalence of polymorphic and irregular VA was confirmed in AM patients with persistent inflammation in follow-up (58%), a predominance of monomorphic and regular VA was found in AM patients after myocarditis healing (42%), as well as in PM patients (all p 0.001).In myocarditis patients, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis.

Background: A new grid mapping catheter (GMC)—allowing for bipolar recordings of the electrograms in each orthogonal direction—became available. The aim of the current study is to evaluate the utility of the GMC in creating substrate and ventricular tachycardia (VT) activation maps during VT ablation procedures. Methods: From December 2017 to July 2018, 41 consecutive patients undergoing a VT ablation procedure using a GMC were studied. During the substrate mapping, 3 different maps were created using the 3 GMC bipolar configurations (along the spline, across the spline, HD wave solution); the low voltage area and late potential areas were compared. In case of inducible VTs, the GMC was used to create the VT activation maps focusing on the diastolic interval. The relation between diastolic activities during VT and substrate abnormality during sinus rhythm was also investigated. Results: The median low-voltage area drawn by the HD wave configuration was 28.9 cm 2 , 13% and 15% smaller than the low-voltage areas identified by the along and across configuration, respectively (33.1 and 33.9 cm 2 ; P P >0.05). VT activation mappings using the GMC were performed in 40 VTs, visualizing the full diastolic pathway in 22 (55%) of them. While the latest late potential areas were included in VT diastolic pathway in 17 VTs, the other 6 VTs showed mismatching of them. Identifying the full diastolic pathway led to a higher ongoing VT termination rate during the ablation than in case of partial recordings (88% versus 45%; P =0.03); furthermore, in the former situation, the noninducibility of the targeted VTs was achieved in all cases. Conclusions: The GMC is a useful tool for performing substrate and VT activation mappings during the VT ablation procedure, precisely identifying the low-voltage areas and quickly visualizing the diastolic pathways.

Objectives This study sought to investigate the incidence of phrenic nerve (PN) limitation and the utility of displacing the PN with a balloon. Background The PN can limit the epicardial ablation of ventricular tachycardia (VT). Methods From 2010 to 2017, 363 patients undergoing VT epicardial ablation at a single center were studied. Before the ablation, we used high output (20-mA) pacing maneuvers to verify the course of the PN. When we observed its capture, we used 1 of 3 different approaches to protect it: 1) non-balloon strategy (nerve-sparing ablation), 2) PN displacement with a small balloon (6 mm × 20 mm), or 3) PN displacement with a large balloon (20 mm × 45 mm). Results PN capture occurred in 25 patients (7%) at the target ablation site. The most common cause was myocarditis (12 patients [48%]), and the incidence of the PN limitation was significantly higher in myocarditis than in other causes (19% vs. 4%, respectively; p = 0.0002). PN displacement was attempted in 7 patients by using large balloons and in 6 patients with small balloons, resulting in successful PN displacements and complete late potential (LP) abolition in 6 patients (86%) and 3 patients (50%), respectively. Among the 12 patients in whom the non-balloon strategy was used, only 1 patient (8%) achieved LP abolition (compared with the large balloon group; p = 0.002), whereas 3 patients experienced PN paralysis. Conclusions The PN limited the epicardial ablation in 7% of patients. Because nerve-sparing ablations often resulted in PN injuries, a possible solution could be to displace the PN with a large balloon, leading to a safer procedure and completion of LP abolition.