Ocrelizumab Alters Cytotoxic Lymphocyte Function While Reducing EBV-Specific CD8+ T-Cell Proliferation in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy. We examined the phenotype and function of cytotoxic lymphocytes and Epstein-Barr virus (EBV)-specific immune responses in people with R-MS before and after ocrelizumab treatment. METHODS: In this prospective study, we collected blood samples from people with R-MS (n = 41) before and 6 and 12 months after initiating ocrelizumab to assess the immune phenotype and the indirect impact on cytotoxic functions of CD8+ T and NK cells. In addition, we evaluated the specific anti-EBV proliferative responses of both CD8+ T and NK lymphocytes as surrogate markers of anti-EBV activity. RESULTS: We observed that while ocrelizumab depleted circulating B cells, it also reduced the expression of activation and migratory markers on both CD8+ T and NK cells as well as their in vitro cytotoxic activity. A comparable pattern in the modulation of immune molecules by ocrelizumab was observed in cytotoxic cells even when patients with R-MS were divided into groups based on their prior disease-modifying treatment. These effects were accompanied by a significant and selective reduction of CD8+ T-cell proliferation in response to EBV antigenic peptides. DISCUSSION: Taken together, our findings suggest that ocrelizumab-while depleting B cells-affects the cytotoxic function of CD8+ and NK cells, whose reduced cross-activity against myelin antigens might also contribute to its therapeutic efficacy during MS.

The Role of SARS-CoV-2 Nucleocapsidic Antigen and Krebs von den Lungen 6 Serum Levels in Predicting COVID-19 Pneumonia Outcome.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a significant threat worldwide, with severe cases leading to hospitalization and death. This study aims to evaluate the potential use of serum nucleocapsid antigen (NAg) and Krebs von den Lungen-6 glycoprotein (KL-6) as biomarkers of severe COVID-19 and to investigate their correlation with clinical, radiological, and biochemical parameters. METHODS: This retrospective study included 128 patients with confirmed SARS-CoV-2 infection admitted to a Neapolitan hospital in Italy between October 2020 and July 2021. Demographic, clinical, and laboratory data were collected, including serum levels of NAg and KL-6. The Chung et al. Computed Tomography Severity Score (TSS) was used to assess the severity of pneumonia, and outcomes were classified as home discharge, rehabilitation, and death. Statistical analyses were performed to compare Group I (home discharge and rehabilitation) and Group II (death, sub-intensive care, and ICU stay) based on demographic data, laboratory parameters, and TSS. RESULTS: Group II patients showed worse outcomes with higher levels of NAg, KL-6, and inflammatory markers, including interleukin-6 (IL-6), interleukin-2 receptor (IL-2R), and adrenomedullin. TSS was also significantly higher in Group II, with a positive correlation between TSS and NAg and KL-6 levels. Group I patients had higher values of hemoglobin (Hb) and platelets (PLT), while Group II patients had higher values of C-reactive protein (CRP), procalcitonin (PCT), D-Dimer, and glycemia. No significant difference was observed in gender distribution. CONCLUSIONS: Serum NAg and KL-6 levels are potential biomarkers of severe COVID-19 pneumonia, with higher levels indicating greater inflammation and organ damage. NAg may help identify infected patients at an increased risk of severe COVID-19 and ensure their admission to the most appropriate level of care. KL-6 may help predict interstitial lung damage and the severity of clinical features. Further studies are needed to establish a decision-making cut-off for these biomarkers in COVID-19.

Mechanisms, prevalence and management of cardiac arrhythmias in cancer patients: a comprehensive review.

Recently, prognosis and survival of cancer patients has improved due to progression and refinement of cancer therapies; however, cardiovascular sequelae in this population augmented and now represent the second cause of death in oncological patients. Initially, the main issue was represented by heart failure and coronary artery disease, but a growing body of evidence has now shed light on the increased arrhythmic risk of this population, atrial fibrillation being the most frequently encountered. Awareness of arrhythmic complications of cancer and its treatments may help oncologists and cardiologists to develop targeted approaches for the management of arrhythmias in this population. In this review, we provide an updated overview of the mechanisms triggering cardiac arrhythmias in cancer patients, their prevalence and management.

Mepolizumab treatment in a patient with previous liver transplantation: One year follow-up.

Severe Asthma (SA) is characterized by inadequate disease control despite maximal inhalation therapy. In November 2021, a 68-years old female patient presented at our facility referring a worsening in her asthma-related symptoms and a high exacerbations rate. She reported a liver transplantation in 2015 and was in treatment with tacrolimus. We started treatment with Mepolizumab 100 mg once every 28 days and monitored her lung function as well as her lymphocytes subsets. After one year follow-up, the patient had a substantial improvement in lung function, exacerbation rate, daily OCS intake dose and no variation in the blood concentration of tacrolimus.

Histology for nephrology, from pre-implantation to post-transplant kidney biopsy. Lesson learned from ReBIrth (Renal BIopsy for Kidney Transplantation Therapy).

A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31st, 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management.

Valor pronóstico del intervalo Tpeak-Tend en el desarrollo de arritmias ventriculares subagudas intrahospitalarias en el síndrome de tako-tsubo / Prognostic value of the Tpeak-Tend interval for in-hospital subacute ventricular arrhythmias in tako-tsubo syndrome

Introducción y objetivos El valor de los parámetros del electrocardiograma (ECG) de repolarización asociados al riesgo de arritmias ventriculares (AVs) en el síndrome de tako-tsubo es controvertido. Nuestro objetivo fue identificar predictores ECG de AVs subagudas, definidas como aquellas ocurridas después de las primeras 48 horas desde el ingreso. Métodos Estudio observacional unicéntrico de pacientes ingresados en el servicio de cardiología entre 2012 y 2018 con diagnóstico de síndrome de tako-tsubo. La recogida de datos incluyó el ECG de 12 derivaciones al ingreso y a las 48 horas, registros de telemetría continua, analíticas, ecocardiografía transtorácica y angiografía coronaria durante la hospitalización. Los eventos de AVs se definieron como: extrasístoles ventriculares ≥ 2.000 en registros de telemetría de 24 horas, fibrilación ventricular, taquicardia ventricular (TV) sostenida, TV polimórfica y TV no sostenida. Resultados Se incluyeron 87 pacientes (edad 72±12 años). Durante una hospitalización mediana de 8 días se registraron AVs subagudas en 22 pacientes (25%) tras una mediana de 91 horas desde el ingreso. Las AVs subagudas se asociaron a aumento de la mortalidad hospitalaria (p=0,030). El intervalo Tpeak-Tend corregido global (promedio de las 12 derivaciones del ECG) a las 48 horas del ingreso fue un predictor independiente de AVs subagudas, superior al intervalo QT corregido (p=0,040). Un valor de corte 108ms en el Tpeak-Tend corregido global mostró una sensibilidad del 71% y especificidad del 72% para AVs subagudas. Conclusiones En pacientes con síndrome de tako-tsubo, las AVs subagudas se asocian a alteraciones de la repolarización que pueden detectarse en el ECG convencional mediante el intervalo Tpeak-Tend (AU)

Introduction and objectives The clinical value of electrocardiogram (ECG) repolarization parameters associated with ventricular arrhythmias (VAs) in tako-tsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48hours from admission. Methods This single-center observational study enrolled patients admitted to the cardiology department between 2012 and 2018 with a confirmed diagnosis of tako-tsubo syndrome. Data collection included a 12-lead ECG on admission and at 48hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography, and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥ 2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT, and non-sustained VT. Results A total of 87 patients (age 72±12 years) were enrolled. During a median of 8 days of hospitalization, subacute VAs were documented in 22 patients (25%) after a median of 91hours from admission. Subacute VAs were associated with an increase in mortality during hospitalization (P=.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48hours from admission was an independent predictor of subacute VAs and was statistically superior to the standard corrected QT interval (Z test, P=.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs. Conclusions In patients with tako-tsubo syndrome, subacute VAs are associated with repolarization alterations that can be identified on conventional ECG using the Tpeak-Tend interval (AU)

Clinical Impact of Cardiac Fibrosis on Arrhythmia Recurrence after Ablation in Adults with Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (ACHD) are often affected by cardiac arrhythmias requiring catheter ablation. Catheter ablation in this setting represents the treatment of choice but is flawed by frequent recurrencies. Predictors of arrhythmia relapse have been identified, but the role of cardiac fibrosis in this setting has not been investigated. The aim of this study was to determine the role of the extension of cardiac fibrosis, detected by electroanatomical mapping, in predicting arrhythmia recurrencies after ablation in ACHD. MATERIALS AND METHODS: Consecutive patients with congenital heart disease and atrial or ventricular arrhythmias undergoing catheter ablation were enrolled. An electroanatomical bipolar voltage map was performed during sinus rhythm in each patient and bipolar scar was assessed according to the current literature data. During follow-up, arrhythmia recurrences were recorded. The relationship between the extent of myocardial fibrosis and arrhythmia recurrence was assessed. RESULTS: Twenty patients underwent successful catheter ablation of atrial (14) or ventricular (6) arrhythmias, with no inducible arrhythmia at the end of the procedure. During a median follow-up period of 207 weeks (IQR 80 weeks), eight patients (40%; five atrial and three ventricular arrhythmias) had arrhythmia recurrence. Of the five patients undergoing a second ablation, four showed a new reentrant circuit, while one patient had a conduction gap across a previous ablation line. The extension of the bipolar scar area (HR 1.049, CI 1.011-1.089, p = 0.011) and the presence of a bipolar scar area >20 cm2 (HR 6.101, CI 1.147-32.442, p = 0.034) were identified as predictors of arrhythmia relapse. CONCLUSION: The extension of the bipolar scar area and the presence of a bipolar scar area >20 cm2 can predict arrhythmia relapse in ACHD undergoing catheter ablation of atrial and ventricular arrhythmias. Recurrent arrhythmias are often caused by circuits other than those previously ablated.

Ventricular tachycardia ablation through radiation therapy (VT-ART) consortium: Concept description of an observational multicentric trial via matched pair analysis.

Introduction: Monomorphic ventricular tachycardia (VT) is a life-threatening condition often observed in patients with structural heart disease. Ventricular tachycardia ablation through radiation therapy (VT-ART) for sustained monomorphic ventricular tachycardia seems promising, effective, and safe. VT-ART delivers focused, high-dose radiation, usually in a single fraction of 25 Gy, allowing ablation of VT by inducing myocardial scars. The procedure is fully non-invasive; therefore, it can be easily performed in patients with contraindications to invasive ablation procedures. Definitive data are lacking, and no direct comparison with standard procedures is available. Discussion: The aim of this multicenter observational study is to evaluate the efficacy and safety of VT-ART, comparing the clinical outcome of patients undergone to VT-ART to patients not having received such a procedure. The two groups will not be collected by direct, prospective accrual to avoid randomization among the innovative and traditional arm: A retrospective selection through matched pair analysis will collect patients presenting features similar to the ones undergone VT-ART within the consortium (in each center independently). Our trial will enroll patients with optimized medical therapy in whom endocardial and/or epicardial radiofrequency ablation (RFA), the gold standard for VT ablation, is either unfeasible or fails to control VT recurrence. Our primary outcome is investigating the difference in overall cardiovascular survival among the group undergoing VT-ART and the one not exposed to the innovative procedure. The secondary outcome is evaluating the difference in ventricular event-free survival after the last procedure (i.e., last RFA vs. VT-ART) between the two groups. An additional secondary aim is to evaluate the reduction in the number of VT episodes comparing the 3 months before the procedure to the ones recorded at 6 months (from the 4th to 6th month) following VT-ART and RFA, respectively. Other secondary objectives include identifying the benefits of VT-ART on cardiac function, as evaluated through an electrocardiogram, echocardiographic, biochemical variables, and on patient quality of life. We calculated the sample size (in a 2:1 ratio) upon enrolling 149 patients: 100 in the non-exposed control group and 49 in the VT-ART group. Progressively, on a multicentric basis supervised by the promoting center in the VT-ART consortium, for each VT-ART patient enrollment, a matched pair patient profile according to the predefined features will be shared with the consortium to enroll a patient that has not undergone VT-ART. Conclusion: Our trial will provide insight into the efficacy and safety of VT-ART through a matched pair analysis, via an observational, multicentric study of two groups of patients with or without VT-ART in the multicentric consortium (with subgroup stratification into dynamic cohorts).

Bifidobacteria modulate immune response in pediatric patients with cow's milk protein allergy.

BACKGROUND: In children with an allergy to cow's milk proteins (CMA), the altered composition of intestinal microbiota influences the immune tolerance to milk proteins (CMP). This study aims to investigate the effect of probiotics on the phenotype and activation status of peripheral basophils and lymphocytes in a pediatric CMA cohort. METHODS: CMA children underwent 45 days of treatment with Bifidobacteria. The basophil degranulation and the immune phenotype of B cells, T helper cells, and regulatory T cells were analyzed in peripheral blood at diagnosis (T0), after a 45-day probiotic treatment (T1), and 45 days after the probiotic wash-out (T2). RESULTS: We observed in probiotic-treated CMA patients a decrease in naive T lymphocytes. Among the CD3+ cell subsets, both naive and activated CD4+ cells resulted markedly reduced after taking probiotics, with the lowest percentages at T2. A decreased basophil degranulation was observed in response to all analyzed CMP at T1 compared to T0. CONCLUSIONS: The probiotic treatment resulted in a decrease of circulating naive and activated CD4+ T cells, as well as degranulating basophils. These data suggest that the Bifidobacteria could have a beneficial effect in the modulation of oral tolerance to CMP. TRIAL REGISTRATION: ISRCTN69069358. URL of registration: https://www.isrctn.com/ISRCTN69069358 . IMPACT: Probiotic treatment with Bifidobacteria induces a reduction of both naive and activated circulating CD4+ T cells in pediatric patients with cow's milk allergy (CMA). The probiotic supplementation induces a decreased basophil degranulation. The immunological tolerance persists even after 45 days of the probiotic wash-out. Bifidobacteria in vivo supplementation down-modulates the activation of innate and adaptive immunity in pediatric patients with cow's milk allergy. Bifidobacteria contribute to the development of immune tolerance in CMA patients.

Mortality after transvenous lead extraction: A risk prediction model for sustainable care delivery.

BACKGROUND AND AIMS: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, the literature about the long-term impact of TLE on survivals is still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective. METHODS: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization-related costs. RESULTS: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range: 1 month-15.5 years), 150 of the 435 enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥77 years, OR: 2.55, CI: 1.8-3.6, p < 0.001), chronic kidney disease (CKD) defined as severe reduction of estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2 , OR: 1.75, CI: 1.24-2.4, p = 0.001) and systolic dysfunction assessed before TLE defined as left ventricular ejection fraction (LVEF) <40%, OR: 1.78, CI 1.26-2.5, p = 0.001. Mean extraction cost was €5011 per patient without reimplantation and €6336 per patient with reimplantation respectively. CONCLUSIONS: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy.

Risk factors for Gram-negative bacterial infection of cardiovascular implantable electronic devices: multicentre observational study (CarDINe Study).

BACKGROUND: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. METHODS: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. RESULTS: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). CONCLUSIONS: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group.

Differential effects of mutations of POPDC proteins on heteromeric interaction and membrane trafficking.

The Popeye domain containing (POPDC) genes encode sarcolemma-localized cAMP effector proteins. Mutations in blood vessel epicardial substance (BVES) also known as POPDC1 and POPDC2 have been associated with limb-girdle muscular dystrophy and cardiac arrhythmia. Muscle biopsies of affected patients display impaired membrane trafficking of both POPDC isoforms. Biopsy material of patients carrying mutations in BVES were immunostained with POPDC antibodies. The interaction of POPDC proteins was investigated by co-precipitation, proximity ligation, bioluminescence resonance energy transfer and bimolecular fluorescence complementation. Site-directed mutagenesis was utilised to map the domains involved in protein-protein interaction. Patients carrying a novel homozygous variant, BVES (c.547G > T, p.V183F) displayed only a skeletal muscle pathology and a mild impairment of membrane trafficking of both POPDC isoforms. In contrast, variants such as BVES p.Q153X or POPDC2 p.W188X were associated with a greater impairment of membrane trafficking. Co-transfection analysis in HEK293 cells revealed that POPDC proteins interact with each other through a helix-helix interface located at the C-terminus of the Popeye domain. Site-directed mutagenesis of an array of ultra-conserved hydrophobic residues demonstrated that some of them are required for membrane trafficking of the POPDC1-POPDC2 complex. Mutations in POPDC proteins that cause an impairment in membrane localization affect POPDC complex formation while mutations which leave protein-protein interaction intact likely affect some other essential function of POPDC proteins.

Rationale and study design of the Italian Registry in the setting of Atrial Fibrillation Ablation with Rivaroxaban - IRIS.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is used routinely to establish rhythm control. There is mounting evidence that CA procedures should be performed during continuous oral anticoagulation and direct oral anticoagulants (DOACs) are considered the first anticoagulation strategy. Few real-life data are now available and even less in the Italian panorama. METHODS: IRIS is an Italian multicenter, non-interventional, prospective study which will be enrolled consecutive AF patients eligible for CA and treated with Rivaroxaban; patients in treatment with Rivaroxaban proceeded directly to CA while Rivaroxaban-naive patients were scheduled for CA after 4 weeks of uninterrupted anticoagulation unless the exclusion of atrial thrombi. Rivaroxaban was uninterrupted or shortly uninterrupted (<24 hours) prior CA, in line with routinely practice of each operator. Patients will be followed on continuous anticoagulation for 1 month after the ablation. The primary efficacy outcome is the cumulative incidence of all-cause death and systemic embolism while the primary safety outcome is the incidence of major bleeding events. The secondary outcomes are represented by non-major bleeding events. All events must be occurred within the first 30 days after the procedure. RESULTS: Two hundred fifty patients are expected to be enrolled and the study is estimated to be completed by the end of 2022. Up to now 56 patients have been enrolled. CONCLUSIONS: This study is the first large Italian prospective study on the management of Rivaroxaban in patients undergoing CA of AF. It aims to depict a comprehensive view of anticoagulation strategy prior CA in several Italian electrophysiology labs.

Ultrasound-guided access to the axillary vein for implantation of cardiac implantable electronic devices: A systematic review and meta-analysis.

The aims of our systematic review were to quantify the expected rate of procedural success, early and late complications during CIED implantation using US-guided puncture of the axillary vein and to perform a meta-analysis of those studies that compared the US technique (intervention) versus conventional techniques (control) in terms of complication rates. MEDLINE, ISI Web of Science, and EMBASE were searched for eligible studies. Pooled Odds Ratio (OR) and Pooled Mean Difference (PMD) for each predictor were calculated. The quality of evidence (QOE) was evaluated according to the GRADE guidelines. Thirteen studies were included a total of 2073 patients. The overall success of US-guided venipuncture for CIED implantation was 96.8%. As regards early complications, pneumothorax occurred in 0.19%, arterial puncture in 0.63%, and severe hematoma/bleeding requiring intervention in 1.1%. No cases of hemothorax, brachial plexus, or phrenic nerve injury were reported. As regards late complications, the incidence of pocket infection, venous thromboembolism, and leads dislodgement was respectively 0.4%, 0.8%, and 1.2%. In the meta-analysis (five studies), the intervention group (US-guided venipuncture) had a trend versus a lower likelihood of having a pneumothorax (0.19% vs 0.75%, p = 0.21), pocket hematoma (0.8% vs 1.7%, p = 0.32), infection (0.28% vs 1.05%, p = 0.29) than the control group, but this did not reach statistical significance. The overall QOE was low or very low. In conclusions we found that the US-guided axillary venipuncture for CIEDs implantation was associated with a low incidence of early and late complications and a steep learning curve.

Prognostic value of the Tpeak-Tend interval for in-hospital subacute ventricular arrhythmias in tako-tsubo syndrome.

INTRODUCTION AND OBJECTIVES: The clinical value of electrocardiogram (ECG) repolarization parameters associated with ventricular arrhythmias (VAs) in tako-tsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48hours from admission. METHODS: This single-center observational study enrolled patients admitted to the cardiology department between 2012 and 2018 with a confirmed diagnosis of tako-tsubo syndrome. Data collection included a 12-lead ECG on admission and at 48hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography, and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥ 2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT, and non-sustained VT. RESULTS: A total of 87 patients (age 72±12 years) were enrolled. During a median of 8 days of hospitalization, subacute VAs were documented in 22 patients (25%) after a median of 91hours from admission. Subacute VAs were associated with an increase in mortality during hospitalization (P=.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48hours from admission was an independent predictor of subacute VAs and was statistically superior to the standard corrected QT interval (Z test, P=.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs. CONCLUSIONS: In patients with tako-tsubo syndrome, subacute VAs are associated with repolarization alterations that can be identified on conventional ECG using the Tpeak-Tend interval.

Mid-Term Outcome of Ventricular Arrhythmias Catheter Ablation in Patients with Chronic Coronary Total Occlusion Compared to Ischemic and Non-Ischemic Patients.

Chronic coronary total occlusions (CTO) are considered an emerging predictor of ventricular arrhythmias (VAs), but currently there are few data on arrhythmic outcomes in patients affected by CTO undergoing radiofrequency catheter ablation of VAs. This study sought to evaluate the impact of unrevascularized CTO on the recurrence of VAs after catheter ablation. This was a single-center retrospective study enrolling 120 patients between 2015 and 2020. All patients were admitted for ventricular tachycardia (VT) or high premature ventricular contractions burden (>25% detected by Holter ECG), without evidence of acute coronary syndrome; they underwent coronary angiography, electrophysiology (EP) study, and three-dimensional electroanatomic mapping (3D-EAM) followed by VAs ablation. Twenty-eight patients (23%) of 120 patients showed CTO at coronary angiography. At baseline, the CTO group presented with higher prevalence of hypertension, chronic renal disease, systolic ventricular dysfunction, secondary prevention ICD implantation, and higher rate of LAVA by 3D-EAM compared with the non-CTO group. At a median follow-up of 15 months (range 1−96 months) after catheter ablation, the only independent predictor of VAs recurrence was the presence of moderate to severe left ventricular (LV) dysfunction. Therefore, the presence of CTO does not predict VAs recurrence after catheter ablation, which is instead predicted by LV dysfunction.

Ultra-high-resolution assessment of lesion extension after cryoballoon ablation for pulmonary vein isolation.

Introduction: Unrecognized incomplete pulmonary vein (PV) isolation during the index procedure, can be a major cause of clinical recurrences of atrial fibrillation (AF) after cryoballoon (CB) ablation. We aimed to characterize the extension of the lesions produced by CB ablation and to assess the value of using an ultra-high resolution electroanatomic mapping (UHDM) system to detect incomplete CB lesions. Materials and methods: Twenty-nine consecutive patients from the CHARISMA registry undergoing AF ablation at four Italian centers were prospectively evaluated. The Rhythmia™ mapping system and the Orion™ (Boston Scientific) mapping catheter were used to systematically map the left atrium and PVs before and after cryoablation. Results: A total of 116 PVs were targeted and isolated. Quantitative assessment of the lesions revealed a significant reduction of the antral surface area of the PV, resulting in an ablated area of 5.7 ± 0.7 cm2 and 5.1 ± 0.8 cm2 for the left PV pair and right PV pair, respectively (p = 0.0068). The mean posterior wall (PW) area was 22.9 ± 2 cm2 and, following PV isolation, 44.8 ± 6% of the PW area was ablated. After CB ablation, complete isolation of each PV was documented by the POLARMap™ catheter in all patients. By contrast, confirmatory UHDM and the Lumipoint™ tool unveiled PV signals in 1 out of 114 of the PVs (0.9%). Over 30-day follow-up, no major procedure-related adverse events were reported. After a mean follow-up of 333 days, 89.7% of patients were free from arrhythmia recurrence. Conclusion: The lesion extension achieved by the new CB ablation system involved the PV antrum, with less than 50% of the PW remaining untouched. The new system, with short tip and circular mapping catheter, failed to achieve PV isolation in only 0.9% of all PVs treated. Clinical trial registration: [http://clinicaltrials.gov/], identifier [NCT03793998].

Short-Term Atrioventricular Dysfunction Recovery after Post-TAVI Pacemaker Implantation.

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4−6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible.

Atrioventricular conduction in PM recipients after transcatheter aortic valve implantation: Implications using Wenckebach point measurement.

Background: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up. Objectives: The aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing. Methods: We enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination. Results: A total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, p < 0.05) and lower ΔMSID (-0.28 ± 3 vs. -3.94 ± 2, p < 0.05). Conclusion: AV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery.