Giovanni Bisignani

Background/Objectives: Heart failure (HF) is associated with substantial morbidity, impaired quality of life (QOL), and reduced functional capacity. In selected patients with symptomatic HF despite Optimal Medical Therapy (OMT), Cardiac Contractility Modulation (CCM) may be a therapeutic option. Identifying patients most likely to benefit from CCM remains an unmet need. The Predict-CCM study aims to evaluate long-term clinical and objective outcomes after CCM therapy and to assess the predictive value of pre-implant low-dose dobutamine stress echocardiography (LDDSE). Methods and Results: Predict-CCM is an independent, non-profit, multicenter, observational cohort study conducted in Italy, with both retrospective and prospective enrollment. The primary endpoint is the proportion of subjects with a clinical response to CCM at 12 months, defined as a ≥1-class reduction in NYHA class. Secondary clinical endpoints include reductions in HF-related hospitalizations, changes in QOL assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and changes in NT-proBNP levels from baseline to follow-up. Outcomes will be evaluated in the overall cohort and in two subcohorts stratified by pre-implant LDDSE response: (1) reduction in left ventricular end systolic volume (LVESV) ≥ 15% (DeltaLVESV ≥ 15%); and (2) reduction in LVESV < 15% (DeltaLVESV < 15%). Assuming a 70% clinical response rate at 12 months, the estimated sample size is 120 patients. The study was approved by the Ethics Committee in March 2025. Enrollment will continue for 2 years, with a 12-month follow-up period after implant for each subject. Conclusions: This study may provide new criteria for patient selection and outcome assessment in CCM therapy. Left ventricular contractile reserve assessed by stress echocardiography may be a promising predictor of response.

Background/Objectives: Two-dimensional echocardiography (2D echo) is widely used for assessing left ventricular ejection fraction (LVEF). This single-center comparative study aims to evaluate the accuracy of LVEF measurements obtained using the AI-assisted handheld ultrasound device Kosmos against cardiac magnetic resonance (CMR), the current gold standard. Methods: A total of 49 adult patients undergoing clinically indicated CMR were prospectively enrolled. AI-based LVEF measurements were compared with CMR using the Wilcoxon signed-rank test, Pearson correlation, multivariable linear regression, and Bland–Altman analysis. All analyses were performed using STATA v18.0. Results: Median LVEF was 57% (CMR) vs. 55% (AI-Echo), with no significant difference (p = 0.51). Strong correlation (r = 0.99) and minimal bias (1.1%) were observed. Conclusions: The Kosmos AI-based autoEF algorithm demonstrated excellent agreement with CMR-derived LVEF values. Its speed and automation make it promising for bedside assessment in emergency departments, intensive care units, and outpatient clinics. This study aims to fill the gap in current clinical evidence by evaluating, for the first time, the agreement between LVEF measurements obtained via Kosmos’ AI-assisted autoEF and those from cardiac MRI (CMR), the gold standard for ventricular function assessment. This comparison is critical for validating the reliability of portable AI-driven echocardiographic tools in real-world clinical practice. However, these findings derive from a selected population at a single Italian center and should be validated in larger, diverse cohorts before assuming global generalizability.

Background: Subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy is expanding rapidly. However, there are few data on the S-ICD replacement procedure. Objective: The aim of this analysis was to describe the procedure and outcome of S-ICD replacement in clinical practice. Methods: From 2013 to 2022, consecutive patients undergoing de-novo implantation of an S-ICD were enrolled at 66 Italian centers of the Rhythm Detect Registry. We analyzed consecutive patients who required S-ICD replacement. Results: 319 S-ICD generators (49 Cameron, 270 Emblem) were replaced for battery depletion. All the procedures were performed in electrophysiology laboratories, by one or two expert operators. In 118 (37%) cases, the replacement was performed as outpatient procedure. The procedure was performed under local anesthesia with or without conscious sedation in 297 patients (93%). The previous S-ICD generator was in an intermuscular pocket in 195 (61%) patients, and in a subcutaneous pocket in the remaining 124 (39%). 39 (31%) generators were shifted from subcutaneous to intermuscular pocket, and their PRAETORIAN score improved from 43±20 to 34±13 (p=0.007). In most cases (308 (97%)), the defibrillation test was not performed after replacement, but the overall PRAETORIAN score was very low (37±28). The S-ICD system was successfully replaced in all patients and no complications were reported; the procedure duration was 39±16 min and was comparable in the case of generator re-implanted in the same pocket or in case of shift to a new pocket. Conclusions: S-ICD replacement was safe and easy to perform, with no peri-operative complications. In clinical practice the replacement procedure is often an opportunity to optimize the position of the generator

Background: The safety and efficacy of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy are well-established. However, there is a paucity of patient-reported outcome data, despite the increasing emphasis on incorporating patients' perspectives into quality care assessments. Current guidelines also recommend evaluating psychological status and addressing distress in defibrillator patients. Purpose: This study aims to assess perioperative and postoperative pain during S-ICD implantation, along with patient acceptance during follow-up. We also explore associations between these outcomes, clinical characteristics, and implantation variables. Methods: A total of 149 consecutive patients (87% male, mean age 53±13 years, body mass index 27±4 Kg/m², ejection fraction 39±14%) who underwent S-ICD implantation across 11 centers were analyzed. Short-term endpoints included pain during and 6 hours after the procedure. Pain intensity was rated on a 10-point visual analogue scale. Long-term endpoint was S-ICD patient acceptance measured (on a 0-to-100 point scale) by the Florida Patients Acceptance Survey (FPAS) score and its components: Return to Function (RTF), Device-Related Distress (DRD), Positive Appraisal (PA), and Body Image Concerns (BIC). The survey was administered 12 months post-implantation. Results: The S-ICD generator was positioned in an intermuscular pocket in 140 (94%) patients. Serratus anterior plane block (SAPB) was performed in 103 (69%) patients. 72 (48%) patients underwent the defibrillation testing. Implantation success was reported in all patients without operative complications. Overall, pain intensity during implantation was 2 [25th-75th percentile: 1-4], and 1 [1-2] for static pain and 2 [1-3] for dynamic pain, 6 hours post-procedure. SAPB was associated with significantly lower pain intensity during implantation (2 [1-3] vs. 4 [2-5], p<0.001) and non-significantly lower values of dynamic pain intensity 6 hours post-procedure (1 [1-2] versus 2 [1-3], p=0.076). The other tested variables, i.e. age, sex, body habitus, ejection fraction, omission of defibrillation testing, were not associated with different pain levels. S-ICD acceptance scores were favorable overall (total FPAS 77 [63-87], RTF 69 [56-88], DRD 25 [10-45], PA 88 [75-100], BIC 13 [0-38]). Patients who underwent SAPB exhibited better RTF (75 [56-88] versus 63 [50-69], p=0.002) and PA (88 [75-100] versus 75 [69-94], p=0.004). Conclusions: S-ICD implantation resulted in minimal discomfort, especially with novel anesthetic techniques. Overall, patients reported good acceptance of the S-ICD. Improved acceptance was observed in patients who underwent SAPB, highlighting the significance of enhanced patient implantation experience for long-term outcomes.

Background: Leading an active lifestyle and participating in recreational sports are crucial for overall well-being and cardiovascular health. Many young patients with implantable defibrillators engage in these activities, but the safety for subcutaneous defibrillator (S-ICD) recipients is unknown. Purpose: Evaluate how lifestyle and recreational sports affect the risk of appropriate (AS) and inappropriate shocks (IAS) in S-ICD recipients. Methods: We enrolled consecutive young S-ICD recipients (14-65 years) from 19 Italian centers and assessed their physical activity with the International Physical Activity Questionnaire (IPAQ). During follow-up, we analyzed the impact of lifestyle and recreational sports on AS and IAS. Results: We enrolled 602 S-ICD recipients (77% males; age: 46±14 years). Common diagnoses included hypertrophic cardiomyopathy (24%), ischemic heart disease (20%), and idiopathic dilated CM (17%). IPAQ was administered 47 months (IQR: 26-68) post-SICD implantation. According to the IPAQ, patients were categorized as inactive subjects (IS; 27.9%), minimally active subjects (MAS; 43.7%), or highly active subjects (HAS; 28.4%). Patients with progressively higher activity levels had, in parallel, younger age (48±14 vs. 45±13 vs. 44±13 years; p=0.02) and higher ejection fraction (EF, %) (46±16 vs. 48±15 vs. 49±16; p=0.09). 163 patients (27.1%) regularly participated in recreational sports, with fitness/gym (25.2%), walking (20.9%), and cycling (14.1%) as the most common choices. As compared to patients not engaged in sports, recreational athletes were younger (43±13 vs 47±14 years; p<0.01) and had higher EF (52±14 vs 46±16; p<0.01). During follow-up (32 months; IQR 19-54), there were 77 discrete VT/VF episodes and 10 storms in 44 patients treated with AS. Also, there were 38 discrete IAS and 7 inappropriate shock storms in 39 patients. IS, MAS and HAS had similar rates of AS (9.5% vs 6.8% vs 5.8%, respectively; p=0.39) and IAS (4.8% vs 6.5% vs 8.2%, respectively; p=0.44). Kaplan-Meier curves showed similar cumulative rate of first AS (p= 0.12) or IAS (p= 0.74) for the 3 groups (Figures 1 and 2). Recreational athletes and non-athletes were propensity matched for age, sex, heart disease, EF, and primary/secondary prevention ICD implantation. Non-athletes and recreational athletes had similar risk of AS (HR: 1.78; 95% CI: 0.75-4.41; p=0.20) and IAS (HR: 1.20; 95% CI: 0.55-2.64; p=0.64). Out of 163 recreational athletes, 7 (4.3%) experienced 12 distinct AS, of which 3 (25%) occurred during sport activities. There were no arrhythmic storms while engaging in sports. Additionally, 15 patients (9.2%) had 17 episodes of IAS, with 3 (17.6%) occurring during sport practice. Conclusions: In young S-ICD recipients, those leading more active lifestyle and commonly engaged in recreational sports were not exposed to a higher risk neither of appropriate, nor of inappropriate shocks. However, shocks related to sport practice were not uncommon.AS-free survival according to IPAQIAS-free survival according to IPAQ

Introduction: Implantable cardiac monitors (ICMs) provide long-term arrhythmia monitoring, but high rates of false detections increase the review burden. The new “SmartECG” algorithm filters false detections. Using large real-world data sets, we aimed to quantify the reduction in workload and any loss in sensitivity from this new algorithm.Methods: Patients with a BioMonitor IIIm and any device indication were included from three clinical projects. All subcutaneous ECGs (sECGs) transmitted via remote monitoring were classified by the algorithm as “true” or “false.” We quantified the relative reduction in workload assuming “false” sECGs were ignored. The remote monitoring workload from five hospitals with established remote monitoring routines was evaluated. Loss in sensitivity was estimated by testing a sample of 2000 sECGs against a clinical board of three physicians.Results: Of our population of 368 patients, 42% had an indication for syncope or pre-syncope and 31% for cryptogenic stroke. Within 418.5 patient-years of follow-up, 143,096 remote monitoring transmissions contained 61,517 sECGs. SmartECG filtered 42.8% of all sECGs as “false,” reducing the number per patient-year from 147 to 84. In five hospitals, nine trained reviewers inspected on average 105 sECGs per working hour. This results in an annual working time per patient of 83 min without SmartECG, and 48 min with SmartECG. The loss of sensitivity is estimated as 2.6%. In the majority of cases where true arrhythmias were rejected, SmartECG classified the same type of arrhythmia as “true” before or within 3 days of the falsely rejected sECG.Conclusion: SmartECG increases efficiency in long-term arrhythmia monitoring using ICMs. The reduction of workload by SmartECG is meaningful and the risk of missing a relevant arrhythmia due to incorrect filtering by the algorithm is limited.

Although real-time 3D echocardiography (RT3DE) has only been introduced in the last decades, its use still needs to be improved since it is a time-consuming and operator-dependent technique and acquiring a good quality data can be difficult. Moreover, the additive value of this important diagnostic tool still needs to be wholly appreciated in clinical practice. This review aims at explaining how, why, and when performing RT3DE is useful in clinical practice.

Background: Fat layers in obese patients can impair R-wave detection and diagnostic performance of a subcutaneous insertable cardiac monitor (ICM). We compared safety and ICM sensing quality between obese patients [body mass index (BMI) ≥ 30 kg/m²] and normal-weight controls (BMI 2) in terms of R-wave amplitude and time in noise mode (noise burden) detected by a long-sensing-vector ICM.Materials and methods: Patients from two multicentre, non-randomized clinical registries are included in the present analysis on January 31, 2022 (data freeze), if the follow-up period was at least 90 days after ICM insertion, including daily remote monitoring. The R-wave amplitudes and daily noise burden averaged intraindividually for days 61–90 and days 1–90, respectively, were compared between obese patients (n = 104) and unmatched (n = 268) and a nearest-neighbour propensity score (PS) matched (n = 69) normal-weight controls.Results: The average R-wave amplitude was significantly lower in obese (median 0.46 mV) than in normal-weight unmatched (0.70 mV, P < 0.0001) or PS-matched (0.60 mV, P = 0.003) patients. The median noise burden was 1.0% in obese patients, which was not significantly higher than in unmatched (0.7%; P = 0.056) or PS-matched (0.8%; P = 0.133) controls. The rate of adverse device effects during the first 90 days did not differ significantly between groups.Conclusion: Although increased BMI was associated with reduced signal amplitude, also in obese patients the median R-wave amplitude was >0.3 mV, a value which is generally accepted as the minimum level for adequate R-wave detection. The noise burden and adverse event rates did not differ significantly between obese and normal-weight patients.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04075084 and NCT04198220.

Introduction: Thoracic impedance (TI) drops measured by implantable cardioverter‐defibrillators (ICDs) have been reported to correlate with ventricular tachycardia/fibrillation (VT/VF). The aim of our study was to assess the temporal association of decreasing TI trends with VT/VF episodes through a longitudinal analysis of daily remote monitoring data from ICDs and cardiac resynchronization therapy defibrillators (CRT‐Ds).Methods and Results: Retrospective data from 2384 patients were randomized 1:1 into a derivation or validation cohort. The TI decrease rate was defined as the percentage of rolling weeks with a continuously decreasing TI trend. The derivation cohort was used to determine a TI decrease rate threshold for a ≥99% specificity of arrhythmia prediction. The associated risk of VT/VF episodes was estimated in the validation cohort by dividing the available follow‐up into 60‐day assessment intervals. Analyses were performed separately for 1354 ICD and 1030 CRT‐D patients. During a median follow‐up of 2.0 years, 727 patients (30.4%) experienced 3298 confirmed VT/VF episodes. In the ICD group, a TI decrease rate of >60% was associated with a higher risk of VT/VF episode in a 60‐day assessment interval (stratified hazard ratio, 1.42; 95% confidence interval (CI), 1.05–1.92; p = .023). The TI decrease preceded (40.8%) or followed (59.2%) the VT/VF episodes. In the CRT‐D group, no association between TI decrease and VT/VF episodes was observed (p = .84).Conclusion: In our longitudinal analysis, TI decrease was associated with VT/VF episodes only in ICD patients. Preventive interventions may be difficult since episodes can occur before or after TI decrease.