Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside.

OBJECTIVES: We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling. BACKGROUND: adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy. METHODS: miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users. RESULTS: At baseline, there were no differences in levels of inflammatory markers, miR-18, miR-145, and miR-181 (p > 0.05) between Non-ARNI users (n 106) and ARNI-users (n 312). At one year of follow-up, ARNI-users vs. Non-ARNI users showed lowest inflammatory markers (p < 0.01) and miR-181 levels (p < 0.01) and higher values of miR-18 (p < 0.01)and miR-145 (p < 0.01). At one year of follow-up, ARNI-users had a higher increase of LVEF (p < 0.01) and 6MWT (p < 0.01) along with a more significant reduction of LVESv (p < 0.01) compared to Non-ARNI users. Cox regression analysis evidenced that ARNI-based therapies increase the probability of anti-remodeling effects of CRTd. Based on symptomatic improvements, echocardiographic and functional classification improvements, 37 (34.9%) patients among ARNI-users became responders, while only twenty (6.4%) patients became responders among Non-ARNi-users. CONCLUSIONS: ARNI might influence epigenetic mechanisms modulating miRs implicated in the adverse cardiac remodeling responses to CRTd.

Leadless pacemaker in Twiddler's syndrome: A case report.

Twiddler's syndrome is a rare cause of pacemaker lead dislodgement. We present the case of a 49-year-old male patient with Down's syndrome implanted with a dual chamber pacemaker showing high ventricular impedance, no sensing, and complete loss of capture for both leads at the 3-month follow-up due to Twiddler Syndrome. The dislocated device was removed, and an endocardial leadless pacing system was implanted.

Leadless AV pacemaker after RF ablation for treatment of bundle branch reentrant ventricular tachycardia: A case report.

In the present article we report the case of a patient at high risk of infection wearing a subcutaneous ICD (S-ICD) due to previous system extractions, hospitalized for symptomatic BBR VT and underwent radiofrequency catheter (RF) ablation. Afterwards, to prevent the possible progression of the infra-His conduction disease to a complete block, it was decided to implant a pacemaker system. Since the high infectious risk, and the patient's firm refusal to implant another transvenous system given the previous extractions he underwent in the past, it was decided to implant a leadless pacemaker with atrioventricular synchrony.

Optimized radiofrequency lesions through local impedance guidance for effective CTI ablation in right atrial flutter.

BACKGROUND: Although radiofrequency (RF) catheter ablation of cavo-tricuspid isthmus (CTI) is an established treatment for typical right atrial flutter (RAFL), it remains to be established whether local tissue impedance (LI) is able to predict effective CTI ablation and what LI drop values during ablation should be used to judge a lesion as effective. We aimed to investigate the ability of LI to predict ablation efficacy in patients with RAFL. METHODS: RF delivery was guided by the DirectSense™ algorithm. Successful single RF application was defined according to a defragmentation of atrial potentials (DAP), reduction of voltage (RedV) by at least 80% or changes on unipolar electrogram (UPC). The ablation endpoint was the creation of bidirectional conduction block (BDB) across the isthmus. RESULTS: 392 point-by-point RF applications were analyzed in 48 consecutive RAFL patients. The mean baseline LI was 105.4 ± 12Ω prior to ablation and 92.0 ± 11Ω after ablation (p < 0.0001). According to validation criteria, absolute drops in impedance were larger at successful ablation sites than at ineffective ablation sites (DAP: 17.8 ± 6Ω vs. 8.7 ± 4Ω; RedV: 17.2 ± 6Ω vs. 7.8 ± 5Ω; UPC: 19.6 ± 6Ω vs. 10.1 ± 5Ω, all p < 0.0001). LI drop values significantly increased according to the number of criteria satisfied (ranging from 7.5Ω to 19.9). BDB was obtained in all cases. No procedure-related adverse events were reported. CONCLUSIONS: A LI-guided approach to CTI ablation was safe and effective in treating RAFL. The magnitude of LI drop was associated with effective lesion formation and BDB and could be used as a marker of ablation efficacy. CLINICAL TRIAL REGISTRATION: Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998.

Localized reentry in the superior vena cava giving rise to an atypical right atrial flutter: Insights from an analysis of two cases.

The superior vena cava is a known arrhythmogenic structure since it can be a non pulmonary vein focus of atrial fibrillation but also a source of fibrillatory activity that in some cases has been reported to mimick atrial flutter. In this report, we demonstrate that another arrhythmogenic mechanism from this vein, that is localized reentry, can cause a specific pattern of atypical right flutter.

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators.

OBJECTIVES: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach. BACKGROUND: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients. METHODS: We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up. RESULTS: We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271-10.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537-6.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 ± 0.72 g vs. 0.58 ± 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 ± 0.29 g vs. 1.18 ± 0.43 g, p 0.001), and the rate of cardiac deaths ( 1.13 ± 0.72 g vs. 0.65 ± 0.69 g, p 0.047). CONCLUSIONS: Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths. Clinical trial ClinicalTrials.gov Identifier NCT04547244.

Novel cryoballoon technology for atrial fibrillation ablation: Impact of pulmonary vein variant anatomy, cooling characteristics, and 1-year outcome from the CHARISMA registry.

BACKGROUND: No data have been reported on cooling characteristics and the impact of variant pulmonary vein (PV) anatomy on atrial fibrillation (AF) recurrences after POLARx cryoballoon (CB) ablation. OBJECTIVE: The purpose of this study was to analyze the impact of PV anatomy variants and cooling characteristics after CB ablation from a large multicenter prospective registry. METHODS: The primary end point was defined as 1-year absence of any atrial tachyarrhythmias (ATAs: AF/atrial flutter/atrial tachycardia). Correlation between ATA recurrences and anatomy variants/cooling characteristics were evaluated. The secondary outcome was the rate of major periprocedural complications. RESULTS: A total of 429 consecutive patients diagnosed with paroxysmal AF (83.4%) or persistent AF (peAF; 16.6%) were enrolled. Twenty-eight patients (6.6%) exhibited an anatomical variant (common ostium: 4.0%; adjunctive PV: 2.6%). Nadir temperature, thaw time, and total deflation time were different between standard PVs and PV variants. After the blanking period, over a mean of 431 ± 99 days of follow-up, 63 patients (14.7%) suffered an ATA recurrence. Patients with recurrences had both a shorter thaw time (18.5 ± 7 seconds vs 19.8 ± 7 seconds; P = .0012) and a shorter total deflation time, whereas time to isolation was longer (57.4 ± 42 seconds vs 49.1 ± 33 seconds; P = .04). Patients with anatomy variants showed a similar ATA recurrence rate (5 of 28 [17.9%]) to the standard PV anatomy group (58 of 401 [14.5%]) (P = .584), with a hazard ratio (HR) of 1.43 (95% confidence interval [CI] 0.49-4.13; log-rank, P = .4384). After adjusting for confounders, heart failure (HR 4.12; 95% CI 1.75-9.73; P = .0013) and peAF (HR 1.81; 95% CI 1.03-3.18; P = .0433) remained associated with ATA recurrence during follow-up. CONCLUSION: The POLARx CB system demonstrated long-term efficacy, along with a safe profile, in both patients with paroxysmal AF and those with peAF, regardless of the presence PV variants. Time to isolation was longer in patients with ATA recurrences during follow-up. CLINICAL TRIAL REGISTRATION: Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice (CHARISMA). CLINICALTRIALS: gov identifier: NCT03793998. Registration date: January 4, 2019.

SGLT2-inhibitors reduce the cardiac autonomic neuropathy dysfunction and vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes: Heart to Mediastinum ratio (H/Mlate), and Washout rate (WR). The SGLT2-I could modulate/reduce autonomic dysfunction in T2DM patients with VVS. This effect could reduce the VVS recurrence in T2DM patients. METHODS: In a prospective multicenter study, after propensity score matching, we studied a population of 324 T2DM patients with VVS, divided into 161 SGLT2-I-users vs. 163 Non-SGLT2-I users. In these patients as SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up. RESULTS: At follow-up end, the SGLT2-I-users vs. Non-SGLT2-I users had best glucose homeostasis and lower values of inflammatory markers, and resting heart rate (p < 0.05). The SGLT2-I-users vs. Non-SGLT2-I users evidenced the lowest low frequency/high frequency ratio (LF/HFr), a significant difference for all the indexes of autonomic dysfunction via ECG Holter analysis, and higher values of H/Mlate (p < 0.05). Finally, comparing SGLT2-I-users vs. Non-SGLT2-I users, we found a higher rate of VVS recurrence events, specifically of the vasodepressor VVS recurrence at 1-year follow-up (p < 0.05). We did not find a significant difference of mixed and cardio-inhibitory VVS recurrence events at 1 year of follow-up in the study cohorts (p > 0.05). At the Cox regression analysis H/Mlate (0.710, [0.481-0.985]), and SGLT2-I therapy (0.550, [0.324-0.934]) predicted all causes of syncope recurrence at 1 year of follow-up. CONCLUSIONS: Non-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence. CLINICAL TRIAL REGISTRATION NUMBER: NCT03717207.

Effects of COVID-19 lockdown on arrhythmias in patients with implantable cardioverter-defibrillators in southern Italy.

Background: The effects of lockdown on non-COVID patients are varied and unexpected. The aim is to evaluate the burden of cardiac arrhythmias during a lockdown period because of COVID-19 pandemics in a population implanted with cardiac defibrillators and followed by remote monitoring. Methods: In this retrospective, multicentre cohort study, we included 574 remotely monitored implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) recipients implanted before January 1, 2019, at seven hospitals in the Campania region, comparing the burden of arrhythmias occurred during the lockdown period because of COVID-19 epidemics (from March 9 to May 1, 2020) with the arrhythmias burden of the corresponding period in 2019 (reference period). Data collection was performed through remote monitoring. Results: During the lockdown period, we observed ventricular tachyarrhythmias (ventricular tachycardia or fibrillation) in 25 (4.8%) patients while in seasonal reference period we documented ventricular tachyarrhythmias in 12 (2.3%) patients; the comparison between the periods is statistically significant (P < .04). Atrial arrhythmias were detected in 38 (8.2%) subjects during the lockdown period and in 24 (5.2%) during the reference period (P < .004). Conclusion: In seven hospitals in the Campania region, during the pandemic lockdown period, we observed a higher burden of arrhythmic events in ICD/CRT-D patients through device remote monitoring.

A New SCN5A Variant in a Patient with Idiopathic Ventricular Fibrillation: The Dark Side of Cardiac Imaging.

We present the case of a patient with recurrent episodes of ventricular fibrillation without evidence of structural cardiac diseases on imaging techniques and negative genetic testing for the most common primary arrhythmia syndromes. A new variant c.6023C>T p.Pro2008Leu of the SCN5A protein, responsible for the sodium inward current (INa) through the cardiomyocytes, was found. A likely pathogenic effect of this gene variant was hypothesized.

Cardiac implantable electronic devices replacements in patients followed by remote monitoring during COVID-19 lockdown.

Aims: Following coronavirus disease (COVID-19) outbreak, the Italian government adopted strict rules of lockdown and social distancing. The aim of our study was to assess the admission rate for cardiac implantable electronic devices (CIEDs) replacement procedures in Campania, the 3rd-most-populous region of Italy, during COVID-19 lockdown. Methods and results: Data were sourced from 16 referral hospitals in Campania from 10 March to 4 May 2020 (lockdown period) and during the same period in 2019. We retrospectively evaluated consecutive patients hospitalized for CIEDs replacement procedures during the two observational periods. The number and type of CIEDs replacement procedures among patients followed by remote monitoring (RM), the admission rate, and the type of hospital admission between the two observational periods were compared. In total, 270 consecutive patients were hospitalized for CIEDs replacement procedures over the two observation periods. Overall CIEDs replacement procedures showed a reduction rate of 41.2% during COVID-19 lockdown. Patients were equally distributed for sex (P = 0.581), and both age [median 76 years (IQR: 68-83) vs. 79 years (IQR: 68-83); P = 0.497]. Cardiac implantable electronic devices replacement procedures in patients followed by RM significantly increased (IR: +211%; P < 0.001), mainly driven by the remarkable increase rate trend of both PM (IR: +475%; P < 0.001) and implantable cardiac defibrillator replacement procedures (IR: +67%, P = 0.01), during COVID-19 lockdown compared with 2019 timeframe. Conclusions: We showed a significant increase trend rate of replacement procedures among CIEDs patients followed by RM, suggesting the hypothesis of its increased use to closely monitoring and to optimize the hospital admission time during COVID-19 lockdown.

Is signal resolution of linear cryocatheters appropriate to map superoparaseptal accessory pathways? A comparison with Orion high-resolution mapping.

Larger tip cryoablation catheters can dampen the signal at the distal tip reducing the resolution of mapping of supero paraseptal APs. The aid of high resolution mapping should be considered to improve safety and efficacy.

Modulation of SERCA in Patients with Persistent Atrial Fibrillation Treated by Epicardial Thoracoscopic Ablation: The CAMAF Study.

OBJECTIVES: To evaluate atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF. BACKGROUND: Reduced levels of SERCA have been reported in the peripheral blood cells of patients with AF. We hypothesize that SERCA levels can predict the response to epicardial ablation. METHODS: We designed a prospective, multicenter, observational study to recruit, from October 2014 to June 2016, patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation. RESULTS: We enrolled 27 patients. Responders (n = 15) did not present AF recurrence after epicardial ablation at one-year follow-up; these patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type natriuretic peptide (BNP), and increased levels of SERCA compared to baseline and to nonresponders (p < 0.05). Furthermore, mean AF duration (Heart rate (HR) 1.235 (1.037-1.471), p < 0.05), Left atrium volume (LAV) (HR 1.755 (1.126-2.738), p < 0.05), BNP (HR 1.945 (1.895-1.999), p < 0.05), and SERCA (HR 1.763 (1.167-2.663), p < 0.05) were predictive of AF recurrence. CONCLUSIONS: Our data indicate for the first time that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Therefore, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments.

Ablating the ventricular insertion of atrio-fascicular mahaim fiber: could be performed safely?

We report a patient who underwent radiofrequency ablation of the distal insertion of an atrio-fascicular accessory pathway with decremental properties because of inability to map a suitable potential alongside the tricuspid annulus. Small, discrete potentials resembling those of Purkinje fiber were found at right ventricular apex. All these potentials showed early activation during tachycardia preceding the QRS onset of various degree. Pace mapping helped to localize the presumed main distal insertion of the atrio-fascicular accessory pathway in a region where damage of the His-purkinje system may ensue. This case report describes catheter ablation of an atriofascicular accessory pathway by targeting its distal (ventricular) insertion site.

Mapping and Ablation of Retrograde Conduction During a Nearly Incessant Pacemaker-mediated Tachycardia in a Patient with Third-degree Atrioventricular Block.

Patients with third-degree atrioventricular block implanted with a dual-chamber pacemaker in DDD mode can develop pacemaker-mediated tachycardias if retrograde ventriculoatrial (VA) conduction is present. Programming a long post-VA refractory period to avoid tachycardia initiation can be contraindicated if these patients have a good atrial response from exercise testing and require a high maximum tracking rate to allow for a proper response to sensed atrial rhythms. We report a case of a patient in whom mapping and ablation of retrograde conduction during the pacemaker-mediated rhythm was the only solution to allow both the programming of a high tracking rate and the elimination of tachycardia induction.

Intrahisian conduction disease and junctional ectopic tachycardia.

Junctional ectopic tachycardia (JET) is an uncommon arrhythmia that mainly affects pediatric patients. However, its clinical presentation may rarely occur in adulthood. Owing to its incessant nature, limited responsiveness to antiarrhythmic agents and poor prognosis, catheter ablation of the junctional focus is often required, even though this may be accompanied by the occurrence of complete atrioventricular block. We report the case of a 68-year-old man with episodes of sustained ventricular tachycardia and repetitive JET whose initiation was often anticipated by a sudden intrahisian conduction delay in the immediately preceding sinus beats.

Intracardiac echocardiography to guide transseptal catheterization for radiofrequency catheter ablation of left-sided accessory pathways: two case reports.

Intracardiac echocardiography (ICE) is a useful tool for guiding transseptal puncture during electrophysiological mapping and ablation procedures. Left-sided accessory pathways (LSAP) can be ablated by using two different modalities: retrograde approach through the aortic valve and transseptal approach with puncture of the fossa ovalis. We shall report two cases of LSAP where transcatheter radiofrequency ablation (TCRFA) was firstly attempted via transaortic approach with ineffective results. Subsequently, a transseptal approach under ICE guidance has been performed. During atrial septal puncture ICE was able to locate the needle tip position precisely and provided a clear visualization of the "tenting effect" on the fossa ovalis. ICE allowed a better mapping of the mitral ring and a more effective catheter ablation manipulation and tip contact which resulted in a persistent and complete ablation of the accessory pathway with a shorter time of fluoroscopic exposure. ICE-guided transseptal approach might be a promising modality for TCRFA of LSAP.

A "multisite" atrioventricular block.

A 6-year-old child, operated for a perimembranous ventricular septal defect, underwent an electrophysiologic study for the presence of first degree atrioventricular (AV) block and bifascicular block with episodes of type 1 and type 2 second degree AV block. Electrophysiologic study showed a considerable infra-His conduction delay (HV interval 170 ms) and spontaneous phases of infra-His type 1 second degree AV block. During incremental atrial pacing supra-His type 1 second degree AV block and 2:1 infra-His AV block were simultaneously observed and this condition persisted unmodified despite the intravenous injection of atropine. The block distal to the His bundle was considered functional.