Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

INTRODUCTION: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. METHODS: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. RESULTS: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). CONCLUSION: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

Prognostic value of right ventricular refractory period heterogeneity in Type-1 Brugada electrocardiographic pattern.

AIMS: To investigate the prognostic significance of heterogeneity in the refractoriness of right ventricular (RV) outflow tract (RVOT) and RV apex at the electrophysiological study (EPS) in Brugada syndrome (BrS). METHODS AND RESULTS: A cohort of BrS patients (primary prevention) from five Italian centres was retrospectively analysed. Patients with spontaneous or drug-induced Type-1 electrocardiogram (ECG) + symptoms were offered an EPS for prognostic stratification. The primary endpoint was a composite of sudden cardiac death (SCD), resuscitated cardiac arrest, or appropriate intervention by the implantable cardioverter-defibrillator (ICD). Three hundred and seventy-two patients with BrS were evaluated (44 ± 15 years, 69% males, 23% with ICD): 4 SCDs and 17 ICD interventions occurred at follow-up (median 48, interquartile range: 36-60 months). Family history of SCD, syncope, and a spontaneous Type-1 ECG pattern were univariate predictors of the primary endpoint in the whole population. In patients undergoing EPS (n = 198, 53%, 44 ± 12 years, 71% males, 39% with ICD), 3 SCD and 15 ICD interventions occurred at follow-up. In this subset, the primary endpoint was not only predicted by ventricular tachycardia/fibrillation inducibility but also by a difference in the refractory period between RVOT and RV apex (ΔRPRVOT-apex) >60 ms. ΔRPRVOT-apex > 60 ms remained an independent predictor of SCD/ICD shock at bivariate analysis, even when adjusted for the other univariate predictors, showing the highest predictive power at C-statistic analysis (0.75, 95% confidence interval 0.63-0.86). CONCLUSIONS: Heterogeneity of RV refractory periods is a strong, independent predictor of life-threatening arrhythmias in BrS patients, beyond VT/VF inducibility at EPS and common clinical predictors.

New cardiac expression of two adenosine-2A receptor isoforms in dysfunctioning minipigs.

PURPOSE: Eight A2AR variants are reported in humans while no A2AR isoforms in pigs. The aim of this study was to evaluate potential isoforms presence in cardiac pig tissue to better define possible involvement of A2AR in the cardiovascular pathophysiology. MATERIALS AND METHODS: In adult male minipigs (n = 4) left ventricular dysfunction (LVD) was induced by pacing at 200 bpm in the right ventricular (RV) apex. In these animals and in sham operated pigs (C-SHAM, n = 4) cardiac tissue was collected from LV-septal wall (LV-SW)-close to pacing site-and from lateral (opposite) site (LV-OSW). A2AR specific primers, derived from Sus scrofa AY772412 sequence, were used for Real-Time PCR. The DNA was sequenced using the Sanger method. Histological analysis was also performed. RESULTS: In LV-SW of LVD minipigs the A2AR melting curves were characterized by a sharp peak between 87 and 91 °C (short isoform, 1-94 bp) on the right of the principal peak corresponding to a long A2AR isoform (GenBank: JQ229674.1) 1-213 bp. As for C-SHAM only one peak was observed in LV-OSW region of LVD animals. The short isoform had an alternative promoter region and a specific translated protein. Histology showed in LVD-LV-SW prominent Purkinje cells compared to LV-OSW and C-SHAM. No difference in A2AR expression was observed between LVD animals and C-SHAM although a slight decrease was observed in LVD-LV-OSW. CONCLUSIONS: The presence of two different isoforms in the myocardium close to the insertion of pacing is suggestive of a differential state-specific expression of A2AR in cardiac tissue.

Near zerO fluoroscopic exPosure during catheter ablAtion of supRavenTricular arrhYthmias: the NO-PARTY multicentre randomized trial.

AIMS: Aim of this study was to compare a minimally fluoroscopic radiofrequency catheter ablation with conventional fluoroscopy-guided ablation for supraventricular tachycardias (SVTs) in terms of ionizing radiation exposure for patient and operator and to estimate patients' lifetime attributable risks associated with such exposure. METHODS AND RESULTS: We performed a prospective, multicentre, randomized controlled trial in six electrophysiology (EP) laboratories in Italy. A total of 262 patients undergoing EP studies for SVT were randomized to perform a minimally fluoroscopic approach (MFA) procedure with the EnSiteTMNavXTM navigation system or a conventional approach (ConvA) procedure. The MFA was associated with a significant reduction in patients' radiation dose (0 mSv, iqr 0-0.08 vs. 8.87 mSv, iqr 3.67-22.01; P < 0.00001), total fluoroscopy time (0 s, iqr 0-12 vs. 859 s, iqr 545-1346; P < 0.00001), and operator radiation dose (1.55 vs. 25.33 µS per procedure; P < 0.001). In the MFA group, X-ray was not used at all in 72% (96/134) of cases. The acute success and complication rates were not different between the two groups (P = ns). The reduction in patients' exposure shows a 96% reduction in the estimated risks of cancer incidence and mortality and an important reduction in estimated years of life lost and years of life affected. Based on economic considerations, the benefits of MFA for patients and professionals are likely to justify its additional costs. CONCLUSION: This is the first multicentre randomized trial showing that a MFA in the ablation of SVTs dramatically reduces patients' exposure, risks of cancer incidence and mortality, and years of life affected and lost, keeping safety and efficacy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01132274.

A proposed index of myocardial staining for vein of Marshall ethanol infusion: an Italian single-center experience.

BACKGROUND: Mitral isthmus (MI) conduction block is a fundamental step in anatomical approach treatment for persistent atrial fibrillation (PeAF). However, MI block is hardly achievable with endocardial ablation only. Retrograde ethanol infusion (EI) into the vein of Marshall (VOM) facilitates MI block. Fluorographic myocardial staining (MS) during VOM-EI could be helpful in predicting procedural alcoholization outcome even if its role is qualitatively assessed in the routine. The aim was to quantitatively assess MS during VOM-EI and to evaluate its association with MI block achievement. METHODS: Consecutive patients undergoing catheter ablation for PeAF at Fondazione Toscana Gabriele Monasterio (Pisa, Italy) from February 2022 to May 2023 were considered. Patients with identifiable VOM were included. A proposed index of MS (MSI) was retrospectively calculated in each included patient. Correlation of MSI with low-voltage zones (LVZ) extension after VOM-EI and its association with MI block achievement were assessed. RESULTS: In total, 42 patients out of 49 (85.8%) had an identifiable VOM. MI block was successfully achieved in 35 patients out of 42 (83.3%). MSI was significantly associated with the occurrence of MI block (OR 1.24 (1.03-1.48); p = 0.022). A higher MSI resulted in reduced ablation time (p = 0.014) and reduced radiofrequency applications (p = 0.002) to obtain MI block. MSI was also associated with MI block obtained by endocardial ablation only (OR 1.07 (1.02-1.13); p = 0.002). MSI was highly correlated with newly formed LVZ extension (r = 0.776; p = 0.001). CONCLUSIONS: In our study cohort, optimal MSI predicts MI block and facilitates its achievement with endocardial ablation only.

Impact of Vein of Marshall Ethanol Infusion Combined with Anatomical Ablation for the Treatment of Persistent Atrial Fibrillation: A Long-Term Follow-Up Based on Implantable Loop Recorders.

BACKGROUND: The best ablation treatment for persistent atrial fibrillation (PeAF) patients is still debated. The vein of Marshall (VOM) seems to be a promising target for ablation and could be combined with a linear set of ablation lesions. The aim of our study is to evaluate the incidence of AF recurrences in a PeAF population treated with a comprehensive ablation approach consisting of VOM ethanol infusion (EI), pulmonary vein isolation (PVI), a left atrial (LA) roofline, a mitral line (guided by the newly formed lesion after alcohol infusion into the VOM and validated by pacing), and a cavotricuspid isthmus line. METHODS: Consecutive patients undergoing the first ablation procedure of catheter ablation (CA) for PeAF were enrolled. All patients underwent VOM-EI, PVI, and ablation lines along the roof of the LA, mitral, and cavotricuspid isthmus. LA voltage mapping before and after VOM-EI was also performed. An implantable loop recorder (ILR) was implanted at the end of the ablation in each patient. RESULTS: Thirty-one consecutive patients (66 ± 8 years and 71% male) affected by PeAF were included in this study. The VOM-EI procedural phase lasted 21.4 ± 10.1 min. PV isolation and lines were validated in all subjects. The ML block was achieved within 10.8 ± 8.7 min. At a mean follow-up of 12 ± 7 months, 27 out of 31 (87%) patients remained free from AT/AF recurrences. Among the patients with recurrences, two (50%) had incomplete ablation lesions and three (75%) had "suboptimal" VOM-EI. In 23/31 patients (74%), antiarrhythmic drugs (AADs) were discontinued after 1 month of follow-up. No significant complications were reported during the follow-up. CONCLUSIONS: this single-center experience demonstrates that VOM-EI systematically combined with an anatomical ablation set in patients with PeAF resulted in feasible, safe, and effective freedom from AF/AT recurrences in 87% of the population after a 1-year follow-up period according to an ILR.

The Subcutaneous Implantable Cardioverter-Defibrillator: A Patient Perspective.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a new technology for the management of ICD patients. But what is the patients' perspective? Previous studies on the transvenous ICD (TV-ICD) showed that device implantation is related not only to anxiety and depression because of the fear of ICD shocks, but also to many biopsychosocial factors like body image changes, perceived reduction of socialization and limitation in professional and sports activities. Anxiety and distress are more evident in younger women because of aesthetic reasons. The scar size and the position of the S-ICD can help these patients and positively influence their social relationships. Moreover, the position of the S-ICD reduces possible complications from catheters due to stress injury and can improve patients' professional life by avoiding some work activity limitations. An S-ICD can be also a good option for athletes in avoiding subclavian crash and reducing inappropriate shocks. However, some questions remain unsolved because an S-ICD is not suitable for patients with indications for pacing, cardiac resynchronization therapy or anti-tachycardia pacing. In conclusion, the use of an S-ICD can assist physicians in reducing the negative impact of implantation on the well-being of some groups of patients by helping them to avoid depression and anxiety as well as improving their noncompliance with their medical treatment.

A mobile app for improving the compliance with remote management of patients with cardiac implantable devices: a multicenter evaluation in clinical practice.

BACKGROUND: The remote device management (RM) is recommended for patients with cardiac implantable electronic devices (CIEDs). RM underutilization is frequently driven by the lack of correct system activation. The MyLATITUDE Patient App (Boston Scientific) has been developed to encourage patient compliance with RM by providing information on communicator setup, troubleshooting, and connection status of the communicator. METHODS: At 14 centers, patients with CIEDs were invited to download and install the App on a mobile device. After 3 months, patients were asked to complete an ad hoc questionnaire to evaluate their experience. RESULTS: The App was proposed to 242 consecutive patients: 81 before RM activation, and 161 during follow-up. The App was successfully installed by 177 (73%) patients. The time required for activation of the communicator and the need for additional support were similar between patients who followed the indications provided by the App and those who underwent standard in-clinic training. During follow-up, notifications of lack of connection were received by 20 (11%) patients and missed transmission by 22 (12%). The median time from notification to resolution was 2 days. After 3 months, 175 (99%) communicators of the 177 patients who installed the App were in "Monitored" status versus 113 (94%) of 120 patients without the App installed (p=0.033). The use of the app made 84% of patients feel reassured. CONCLUSIONS: The App was well accepted by CIED patients and offered support for communicator management and installation. Its use enabled patients to remain connected with greater continuity during follow-up.

Reverse left ventricular remodeling is more likely in non ischemic cardiomyopathy patients upgraded to biventricular stimulation after chronic right ventricular pacing.

BACKGROUND: Chronic right ventricular (RV) apical pacing may lead to left ventricular (LV) dyssynchrony and LV dysfunction. In heart failure due to RV pacing, upgrading to biventricular stimulation (CRT) can improve NYHA Class and LV function. A proportion of patients do not respond to upgrading. Aim was to assess whether etiology of LV dysfunction accounts for responses to CRT in RV-paced patients. METHODS: Sixty-two patients treated by CRT, under RV pacing from 50.2 ± 5.4 months, were studied. Cause of LV dysfunction was non-ischemic (NIC) in 28 and ischemic cardiomyopathy (IC) in 34 patients. Clinical and conventional echocardiographic parameters were available within 1 month before RV pacing, within 1 month before CRT and at 12 ± 2 months of follow-up (FU). RESULTS: Decreased LVEF (from 37.0 ± 8.8 to 25.6 ± 6.1%, p <0.001), increased LV end-systolic dimensions (LVESD) (from 48.1 ± 8.6 to 55.2 ± 7.9 mm, p <0.001) and worsened NYHA Class (from 1.9 ± 1.1 to 3.2 ± .6, p < 0.005) were found before CRT, compared to pre RV-pacing. After CRT, 44/62 patients showed a ≥ 1 NYHA Class improvement; >10% decrease in LVESD was observed in 24 patients: 5 with IC, 19 with NIC (p < .0.001). The association between cause of LV dysfunction with >10% decrease in LVESD remained highly significant (p < 0.001) adjusting for pre-CRT QRS duration, NYHA Class, LVEF, LVESD, treatment or RV pacing duration. CONCLUSIONS: CRT improves functional class even after long-lasting pacing. Reverse remodeling is evident in a small population, more likely with NIC.

[Late dislocation of the left ventricular lead as a cause of clinical and functional worsening during cardiac resynchronization therapy]. / La dislocazione tardiva del catetere in seno coronarico come causa di rapido peggioramento clinico e funzionale durante resincronizzazione cardiaca.

Efficacy of cardiac resynchronization therapy (CRT) in heart failure is also related to correct positioning of the left ventricular lead. We report the case of a patient treated by CRT who presented, after 6 years of implantation, rapid clinical and functional worsening due to dislodgment of the left ventricular lead.

[Role of biomarkers in the detection of sub-clinical myocardial injury: H-FABP and radiofrequency ablation of ventricular arrhythmias]. / Utilità dei biomarcatori nella valutazione del danno cardiaco subclinico: H-FABP e ablazione in radiofrequenza delle aritmie ventricolari.

The importance of biomarker assay such as cardiac troponins and H-FABP is assuming a pivotal role not only in the diagnosis and follow-up of patients with acute coronary syndromes. Radiofrequency (RF) ablation represents a widely used method for the non pharmacologic treatment of arrhythmias.We report a case of a patient complaining of life-threatening arrhythmias treated by RF in whom temporal changes of cardiac biomarkers was determined after the procedure.

[Adrenomedullin plasma levels as indicators of prognosis after cardiac resynchronization therapy]. / Livelli plasmatici di adrenomedullina come indicatori di prognosi dopo terapia di resincronizzazione cardiaca.

The cardiac resynchronization therapy (CRT), based on correction of electro-mechanical dyssynchrony by biventricular pacing in patients with severe chronic HF unresponsive to optimal medical treatment and left ventricular conduction disturbances, has been developed. The determination of plasma adrenomedullin (ADM) levels before implantation could provide important additional information to reduce the high percentage (30%) of patients not responding to treatment despite the use of increasingly sophisticated methods for selecting candidates. The case described illustrates the importance of basal ADM plasma levels in predicting the clinical and functional improvement after treatment with CRT.

Catheter cryoablation of ventricular ectopy originating from his region.

Careful mapping, early detection of AV conduction damage and cryothermal energy availability are essential in dealing with ablation procedures at the parahisian region.

The extent and location of late gadolinium enhancement predict defibrillator shock and cardiac mortality in patients with non-ischaemic dilated cardiomyopathy.

BACKGROUND: In non-ischaemic dilated cardiomyopathy (NIDCM), it is uncertain which late gadolinium enhancement (LGE) pattern, extent and location predict ventricular arrhythmias. METHODS: We analysed 183 NIDCM patients (73% men, median age 66 years) receiving an implantable cardioverter defibrillator (ICD) for primary prevention, undergoing cardiac magnetic resonance within 1 month before implantation. The primary endpoint was appropriate ICD shock, the secondary endpoint was a composite of appropriate ICD shock and cardiac death. RESULTS: LGE was found in 116 patients (63%), accounting for 9% of LV mass (5-13%). Over a 30-month follow-up (10-65), 20 patients (11%) experienced the primary and 30 patients (16%) the secondary endpoint. LGE presence, inferior wall LGE, diffuse (≥2 wall) LGE, the number of segments with LGE, the number of segments with 50-75% transmural LGE, and percent LGE mass were univariate predictors of both endpoints. Also septal LGE predicted the primary, and lateral LGE predicted the secondary endpoint. LGE limited to right ventricular insertion points did not predict any endpoint. Percent LGE mass had an area under the curve of 0.734 for the primary endpoint, with 13% as the best cut-off (55% sensitivity, 86% specificity, 32% PPV, 94% NPV), conferring a 7-fold higher risk compared to patients with no LGE or LGE <13%. Survival free from both endpoints was significantly worse for patients with LGE ≥13%. CONCLUSIONS: In patients with NIDCM receiving a defibrillator for primary prevention, LGE presence and extent predicted appropriate ICD shock and cardiac mortality; also specific LGE patterns and locations predicted a worse prognosis.

Rationale, study design, and pilot phase of tHE Management of AntiThrOMbotic therApy (HEMATOMA) in patients undergoing electrophysiological device surgery: Italian National Multicenter Observational REgistry.

AIMS: To investigate the different strategies adopted for the management of antithrombotic therapy and the related hemorrhagic and infective complication rates in patients undergoing cardiac implantable electronic devices (CIEDs) surgery in a real-world setting. METHODS: THE Management of AntiThrOMbotic therApy in patients undergoing electrophysiological device surgery: Italian NatiOnal Multicenter Observational REgistry (HEMATOMA NO MORE) is an observational, prospective, multicenter, national cohort study (with a retrospective, multicenter, regional pilot phase) designed to enroll patients with standard indications to CIED implantations/replacements receiving concomitant antithrombotic therapy. The primary outcome is clinically significant pocket hematoma defined as a postprocedural hematoma, resulting in prolonged hospitalization and/or requiring interruption of antithrombotic therapy and/or requiring further surgery and/or requiring transfusion. RESULTS: The pilot phase included 569 patients from 11 centers in Tuscany enrolled between September 2014 and May 2015 and followed up for 1 month. Patients were categorized according to the strategy of management of antithrombotic therapy, with heparin bridging being associated with the highest incidence of clinically significant pocket hematoma (12.3%). Overall nonpocket hemorrhagic events rate was quite low (0.52%) and thromboembolic complications were negligible (0.17%). CONCLUSION: Occurrence of pocket hematoma in patients undergoing CIED surgery is largely influenced by the strategy of management of antithrombotic therapy. The HEMATOMA NO MORE will assess the impact of different strategies on the risk of developing pocket hematoma and of subsequent CIED-related infections.

Statin intolerance in heterozygous familial hypercolesterolemia with cardiovascular disease: After PCSK-9 antibodies what else?

Background Familial hypercholesterolemia is the elective clinical condition that deserves the maximal personalisation in lipid-lowering therapy, especially in the presence of statin intolerance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a promising approach to lower low-density lipoprotein (LDL) cholesterol. Methods We enrolled 18 patients (mean age 62 ± 8 years, 72% men) affected by heterozygous familial hypercholesterolemia and cardiovascular disease, with a history of statin intolerance assigned to PCSK9 inhibitors. Six patients were also on LDL apheresis. Associated Lp(a)-hyperlipoproteinemia (defined as >60 mg/dl) was observed in two out of 18 subjects. PCSK9 inhibitor injectable monoclonal antibodies were administered, every 2 weeks, on top of patient therapy for 12 ± 4 weeks (evolocumab in 15 subjects, alirocumab in three subjects). Results After 3 months (12 ± 4 weeks) of therapy, a decrease in total cholesterol (-35%), LDL cholesterol (-51%) and Lp(a) levels (-20%) was observed. Five out of 18 patients reached LDL cholesterol levels of <70 mg/dl, seven showed LDL cholesterol values between 71 and 100 mg/dl, and six out of 18 still had LDL cholesterol levels above 100 mg/dl. Among the six patients with LDL cholesterol levels >100 mg/dl, three were already on LDL apheresis before the PCSK9 inhibitor treatment, while three were referred to LDL apheresis treatment. Adverse events were reported in two out of 18 patients on evolocumab: one presented with flu-like syndrome and the other reported episodes of mild difficulty in maintaining concentration. Conclusions PCSK9 inhibitors represent a novel therapeutic tool for patients with familial hypercholesterolemia who are intolerant to statins. However, more data are needed before cleaning up the old therapeutic armamentarium, such as LDL apheresis, which is likely to preserve its valuable role also in the new lipid-lowering era.

Heart-type fatty acid binding protein is an early marker of myocardial damage after radiofrequency catheter ablation.

OBJECTIVES: Radiofrequency (RF) ablation of arrhythmias induces myocardial damage and release of biomarkers. This study aimed to assess the kinetics of heart-type fatty acid-binding protein (h-FABP), a cytosolic protein released after myocardial injury incurred by both atrial and ventricular RF ablation, compared to other markers of myocardial injury. DESIGN AND METHODS: h-FABP, cTnI, CK-MB(mass) and myoglobin were evaluated in 30 patients with atrial or ventricular tachyarrhythmias before, immediately after and at 3, 6 and 24h after the procedure. RESULTS: h-FABP increased immediately after the procedure in all subjects (6.6 ± 1.2 µg/L vs 2.7 ± 0.3, p<0.001) but increased significantly only in ventricular ablations. The peak of h-FABP significantly correlates with the values of time for mean power of RF application in both the entire patient cohort and in ventricular ablations. CONCLUSIONS: h-FABP may be an early parameter for monitoring RF-induced lesions and the site of ablation was relevant for biomarker increase.