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Carlo Lavalle, Martina Straito, Annalisa Caroli, Agostino Piro, Giuseppe Giunta, Marco Valerio Mariani, Francesco FedeleDepartment of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, “Sapienza” University of Rome, Policlinico Umberto I, Rome, ItalyAbstract: Currently, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population, representing a powerful risk factor for stroke and systemic thromboembolism and increased mortality and morbidity. Restoration of sinus rhythm is an important treatment option in AF and has a high success rate, but there is the need for an effective anticoagulation strategy to reduce the risk of embolic events. Anticoagulation with vitamin K antagonists is often associated with failure to achieving effective international normalized ratio. In this setting, recent data have led to extended approval for rivaroxaban in clinical practice, because it is effective and safe in patients with AF undergoing cardioversion, avoiding additional health costs and related time loss, while improving patient satisfaction. The present report provides an overview of the main randomized controlled trial and the main real-life studies, documenting the use of rivaroxaban in patients with non-valvular AF who underwent the cardioversion procedure. Considering that novel non-vitamin K antagonist oral anticoagulants in left atrial appendage thrombi resolution is still unknown in the real-world practice, the main findings on the use of rivaroxaban in this setting are also discussed.Keywords: atrial fibrillation, cardioversion, novel oral anticoagulants, rivaroxaban, thrombus

Gianfranco Piccirillo,1 Federica Moscucci,1 Fabiola Mastropietri,1 Claudia Di Iorio,1 Marco Valerio Mariani,1 Marcella Fabietti,1 Gaetana M Stricchiola,1 Ilaria Parrotta,1 Gennaro Sardella,1 Massimo Mancone,1 Damiano Magrì2 1Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, “La Sapienza” University of Rome, Rome, Italy; 2Department of Molecular and Clinical Medicine, S. Andrea Hospital, “Sapienza” University of Rome, Rome, Italy Objectives: To evaluate the predicative power of the electrical risk score (ERS), a noninvasive and inexpensive test obtained by means of a standard 12-lead electrocardiogram (ECG), in a cohort of elderly patients who had undergone transcatheter aortic valve replacement (TAVR).Methods: Survivors and non-survivors after TAVR at 1-year follow-up were compared in respect to the pre-procedural ERS as well as a number of other clinical and instrumental variables. ERS is composed of seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms); left ventricular hypertrophy (Sokolow–Lyon criteria); delayed QRS transition zone (≥ V4); frontal QRS-T angle (>90°); long QTBazett (>450 ms for men and >460 in women) or JTBazett (330 ms for men and >340 ms for women); and long Tpeak to Tend interval (Tp-e) (>89 ms). The trial was registered in ClinicalTrials.gov as NCT03145376.Results: A total of 40 patients were evaluated. During the follow-up, the all-cause mortality rate was 25% (ten patients) with 15% of cardiovascular death (six patients). The ERS was the strongest predictor of all-cause (odds ratio 3.73, 95% CI: 1.44–9.66, P

Cardiac contractility modulation (CCM) signals are non-excitatory signals that are applied during the myocyte's absolute refractory period. These signals have been demonstrated to have an inotropic effect without increasing myocardial oxygen consumption. This has been observed in both preclinical animal studies and randomized clinical trials. CCM influences the expression of various genes that are abnormally expressed in heart failure: it reverses fetal myocyte gene programming associated with heart failure and regulates the expression of genes associated with calcium cycling and myocardial contractile machinery. Clinical investigations have primarily focused on patients with heart failure and normal QRS duration where CCM has demonstrated its safety and effectiveness in reducing heart failure-related hospitalizations, as well as improving symptoms, functional capacity, and overall quality of life. Currently, for individuals experiencing symptomatic heart failure with an ejection fraction ranging from 25% to 45% and a QRS duration of less than 130 ms, who are not suitable candidates for cardiac resynchronization therapy, CCM offers a viable treatment option. Even though promising results in specific HF subgroups have been published, further studies are needed to understand the role of CCM in tailored treatment for heart failure. Moreover, the role of multimodality imaging in lead placement and prognostic stratification in CCM patients should be further investigated. This review aims to summarize the main pathophysiological evidence related to the use of CCM and to highlight its role as a possible additional weapon in tailored treatment for specific subgroups of patients with heart failure.

Heart failure (HF) is a complex syndrome that requires tailored and patient-centered treatment. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) constitute one of the four pillars of the medical treatment of HF. However, the 2023 ESC guidelines treat HF as a single entity without making clear distinctions in phenotypes according to etiology. This creates a "gap in knowledge", causing much debate about the applicability of these drugs in peculiar clinical settings that are etiological and/or predisposing clinical conditions for HF. Furthermore, considering the variety of etiologies and different pathophysiological backgrounds of HF, one might question whether the use of SGLT2is is equally beneficial in all types of HF and whether certain drug-related properties may be exploited in different contexts. For example, SGLT2is can improve the metabolic and inflammatory state, which is fundamental in ischemic heart disease. Anti-inflammatory power can also play a paramount role in myocarditis or cardiotoxicity, while improving the congestive state and reducing filling pressure may be even more fundamental in restrictive heart disease or advanced heart disease. This review aims to gather the evidence currently present in the literature concerning the advantages or the disadvantages of using these drugs in these particular clinical settings, with the goal being an optimized and highly personalized treatment for HF.

Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing the risk of infection. The role of antibiotic prophylaxis in infection prevention is crucial, including the emerging use of antibiotic-supported tools and other local antibiotic delivery systems, which may reduce the risk of infection at the device implant site. In this contemporary review, we provide an overview of the prophylactic treatment and different antibiotic regimens for the treatment of CDIs, emphasizing early diagnosis, appropriate choice of antibiotics, and individualized treatment.

The exploration of the cardiac conduction system evolved over a century, marked by groundbreaking discoveries in atrioventricular (AV) nodal physiology. Atrioventricular nodal re-entrant tachycardia (AVNRT), the most prevalent regular tachycardia in humans, remains enigmatic despite extensive research. Detailed examinations of AV nodal anatomy and histology reveal variations in location and shape, influencing electrophysiological properties. Variability in AV nodal extensions and their embryological origins contribute to the complexity of the conduction system. Physiologically, the AV node plays a crucial role in modulating AV conduction, introducing delays for ventricular filling and filtering atrial impulses. Dual-pathway physiology involving fast and slow pathways further complicates AVNRT circuitry. Integrated approaches combining pre-procedural imaging with electroanatomical mapping enhance our understanding of AV nodal structures and high-definition mapping improves precision in identifying ablation targets. Electrophysiological-anatomical correlations may unveil the specific roles of conduction axis components, aiding in the optimization of ablation strategies. This review traces the historical journey from Tawara's pioneering work to recent integrated approaches aimed at unraveling the intricacies of AV nodal structures while emphasizing the importance of a multidimensional approach, incorporating technological advancements, anatomical understanding, and clinical validation in human mapping studies.

Introduction: The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF., Methods: This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up., Results: The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135)., Conclusions: In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalization during the vulnerable phase after discharge, compared with  a conventional stepwise approach., (© 2024. The Author(s).)

Introduction: Gliflozins are recommended as first-line treatment in patients with heart failure and/or cardiovascular comorbidities and are demonstrated to reduce atrial fibrillation (AF) occurrence. However, it is not well known which gliflozin yields the larger cardioprotection in terms of AF occurrence reduction. Hence, we aimed to compare data regarding AF recurrence associated with different gliflozins., Methods: An accurate search of online scientific libraries (from inception to June 1, 2023) was performed. Fifty-nine studies were included in the meta-analysis involving 108 026 patients, of whom 60 097 received gliflozins and 47 929 received placebo., Results: Gliflozins provided a statistically significant reduction of AF occurrence relative to standard of care therapy in the overall population (relative risks [RR]: 0.8880, 95% CI: [0.8059; 0.9784], p = .0164) and in patients with diabetes and cardiorenal diseases (RR: 0.8352, 95% CI: [0.7219; 0.9663], p = .0155). Dapagliflozin significantly decreased AF occurrence as compared to placebo (0.7259 [0.6337; 0.8316], p < .0001) in the overall population, in patients with diabetes (RR: 0.2482, 95% CI: [0.0682; 0.9033], p = .0345), with diabetes associated with cardiorenal diseases (RR: 0.7192, 95% CI: [0.5679; 0.9110], p = .0063) and in the subanalysis including studies with follow-up ≥1 year (RR: 0.7792, 95% CI: [0.6508; 0.9330], p = .0066). No significant differences in terms of AF protection were found among different gliflozins., Conclusions: Dapagliflozin use was associated with significant reduction in AF risk as compared to placebo in overall population and patients with diabetes, whereas the use of other gliflozins did not significantly reduce AF occurrence., (© 2024 Wiley Periodicals LLC.)

Background: The long-term success rate of pulmonary vein isolation (PVI) is suboptimal due to the presence of non-pulmonary vein (PV) foci that can trigger atrial fibrillation (AF) in up to 11%. Among non-PV triggers, the superior vena cava (SVC) is a major site of origin of ectopic beats initiating AF., Objective: To compare data from randomized controlled trials (RCTs) assessing PVI + empiric SVC isolation (SVCI) versus PVI alone in terms of AF recurrence, procedure-related complications, and fluoroscopic and procedural times., Methods: A search of online scientific libraries (from inception to April 1, 2024) was performed. Four RCTs were considered eligible for the meta-analysis totaling 600 patients of whom 287 receiving PVI + SVCI and 313 receiving PVI alone., Results: In the overall population, SVCI + PVI was associated with a non-significant reduction of AF recurrence at follow-up (0.66 [0.43;1.00], p = 0.05, I 2 0%). In patients with paroxysmal AF (PAF), a significant reduction of AF recurrence was related to SVCI + PVI (11.7%) as compared to PVI alone (19.9%) (0.54 [0.32;0.92], p = 0.02, I 2 0%). No statistical differences were found among the groups in terms of fluoroscopic (3.31 [- 0.8;7.41], p = 0.11, I 2  = 91%), procedural times (5.69 [- 9.78;21.16], p = 0.47, I 2  = 81%), and complications (1.06 [0.33;3.44], p = 0.92, I 2  = 0%)., Conclusion: The addition of SVCI to PVI in patients in PAF is associated with a significant lower rate of AF recurrence at follow-up, without increasing complication rates and procedural and fluoroscopy times., (© 2024. The Author(s).)

Background: Typical isthmus-dependent atrial flutter (AFL) is traditionally treated through radiofrequency (RF) ablation to create a bidirectional conduction block across the cavo-tricuspid isthmus (CTI) in the right atrium. While this approach is successful in many cases, certain anatomical variations can present challenges, making CTI ablation difficult., Methods: We enrolled four patients with typical counter-clockwise AFL who displayed an epicardial bridge at the CTI. Patients underwent high-resolution mapping of the right atrium and CTI ablation., Results: Post-mapping identified areas of early focal activation outside the lesion line which suggested the presence of an epi-endocardial bridge with an endocardial breakthrough, confirmed by recording a unipolar rS pattern on electrograms at that site. A stable CTI block was achieved in all patients only after ablation at the site of the epi-endocardial breakthrough., Conclusions: The presence of an epicardial bridge at the CTI, allowing conduction to persist despite endocardial ablation, should be considered in challenging cases of CTI-dependent AFL. Understanding this phenomenon and utilizing appropriate mapping and ablation techniques are essential for achieving successful and lasting CTI block., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Matteucci, Pandozi, Russo, Galeazzi, Lombardi, Mariani, Lavalle and Colivicchi.)

Pregnancy entails notable physiological alterations and hormonal fluctuations that affect the well-being of both the fetus and the mother. Cardiovascular events and arrhythmias are a major concern during pregnancy, especially in women with comorbidities or a history of arrhythmias. This paper provides an overview of the prevalence, therapies, and prognoses of different types of arrhythmias during pregnancy. The administration of antiarrhythmic drugs (AADs) during pregnancy demands careful consideration because of their possible effect on the mother and fetus. AADs can cross the placenta or be present in breast milk, potentially leading to adverse effects such as teratogenicity, growth restriction, or premature birth. The safety profiles of different classes of AADs are discussed. Individualized treatment approaches and close monitoring of pregnant women prescribed AADs are essential to ensure optimal maternal and fetal outcomes.

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02-0.078) and 0.031 ng/mL (IQR 0.02-0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median ( p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization ( p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02-4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006-3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH ( p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events ( p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death ( p = 0.01) and CV death/HFH ( p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death ( p < 0.001) and CV death/HFH ( p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

Background: Catheter ablation (CA) of atrial fibrillation is routinely used to obtain rhythm control. Evidence suggest that catheter ablation should be done during uninterrupted oral anticoagulation., Methods: Italian Registry in the setting of atrial fibrillation ablation with rivaroxaban (IRIS) is an Italian multicenter, non-interventional, prospective study which enrolled 250 consecutive atrial fibrillation patients eligible for catheter ablation on rivaroxaban. The decision for rivaroxaban management was left to the physician: uninterrupted or shortly interrupted prior to Catheter ablation. Patients received a follow-up visit at 1 month and 12 months after the procedure., Results: The primary outcome, represented by all-cause death and systemic embolism at 1 month and 12 months was characterized by one transient ischemic attack and one myocardial infarction in the first 30 days. Both events happened in patients with shortly interrupted strategy (P=0.147), and both in patients who underwent radiofrequency ablation (P=0.737). In the primary safety outcome represented by major bleeding we did not register any event in the 12-month follow-up. The secondary outcome constituted by minor bleeding registered 1 event, after the first 30 days since CA., Conclusions: IRIS is the biggest real-life data registry regarding CA ablation on rivaroxaban in Italian setting, proving the safety and efficacy of rivaroxaban.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

Ventricular tachycardias (VTs) and electrical storms (ES) are life-threatening conditions mostly seen in the setting of structural heart disease (SHD). Traditional management strategies, predominantly centered around pharmacological interventions with antiarrhythmic drugs, have demonstrated limited efficacy in these cases, whereas catheter ablation is related with more favorable outcomes. However, patients with hemodynamically unstable, recurrent VT or ES may present cardiogenic shock (CS) that precludes the procedure, and catheter ablation in patients with SHD portends a multifactorial intrinsic risk of acute hemodynamic decompensation (AHD), that is associated with increased mortality. In this setting, the use of mechanical circulatory support (MCS) systems allow the maintenance of end-organ perfusion and cardiac output, improving coronary flow and myocardial mechanics, and minimizing the effect of cardiac stunning after multiple VT inductions or cardioversion. Although ablation success and VT recurrence are not influenced by hemodynamic support devices, MCS promotes diuresis and reduces the incidence of post-procedural kidney injury. In addition, MCS has a role in post-procedural mortality reduction at long-term follow-up. The current review aims to provide a deep overview of the rationale and modality of MCS in patients with refractory arrhythmias and/or undergoing VT catheter ablation, underlining the importance of patient selection and timing for MCS and summarizing reported clinical experiences in this field.

Background: The probability of spontaneous conversion (SCV) to sinus rhythm (SR) in patients presenting to the emergency department (ED) with hemodynamically stable, symptomatic atrial fibrillation (AF) is not well known. Objective: To develop and validate a score to determine the probability of SCV to SR in patients presenting to the ED with hemodynamically stable, symptomatic AF. Methods: This retrospective, observational study enrolled consecutive patients admitted with AF to the ED. Variables associated to SCV during a 6 h "wait-and-see" approach were used to develop and validate a score to determine the probability of SCV to SR in AF patients. The study was divided in two phases: (1) score development and (2) validation of the predictive score. Results: Out of 748 eligible patients, 446 patients were included in the derivation cohort, whereas 302 patients were included in the validation cohort. In the derivation cohort, based on multivariable logistic analysis, a probability score weight was developed including: previous SCV (3 points), AF-related symptom duration < 24 h (5 points), age ≥ 65 years (3 points) and female sex (2 points). The score allowed us to divide patients in three groups based on the probability of SCV to SR during the 6 h observation period. The probability prediction model showed an area under the curve (AUC) of 0.707 and 0.701 in the derivation and validation cohorts, respectively. Conclusions: The proposed score allowed us to predict SCV probability with good accuracy and may help physicians in tailoring AF management in an effective and timely manner.

Background: The mechanism of typical slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) and its anatomical and electrophysiological circuit inside the right atrium (RA) and Koch's Triangle (KT) are not well known., Objective: To identify the potentials of the compact AV node and inferior extensions and to perform accurate mapping of the RA and KT in sinus rhythm (SR) and during AVNRT, to define the tachycardia circuit., Methods: Consecutive patients with typical AVNRT were enrolled in 12 Italian centers and underwent mapping and ablation by means of a basket catheter with small electrode spacing for ultrahigh-density mapping and a modified signal-filtering toolset to record the potentials of the AV nodal structures., Results: Forty-five consecutive cases of successful ablation of typical slow-fast AVNRT were included. The mean SR cycle length (CL) was 784.1 ± 6 ms and the mean tachycardia CL was 361.2 ± 54 ms. The AV node potential had a significantly shorter duration and higher amplitude in sinus rhythm than during tachycardia (60 ± 40 ms vs. 160 ± 40 ms, p < .001 and 0.3 ± 0.2 mV vs. 0.09 ± 0.12 mV, p < .001, respectively). The nodal potential duration extension was 169.4 ± 31 ms, resulting in a time-window coverage of 47.6 ± 9%. The recording of AV nodal structure potentials enabled us to obtain 100% coverage of the tachycardia CL during slow-fast AVNRT., Conclusion: Detailed recording of the potentials of nodal structures is possible by means of multipolar catheters for ultrahigh-density mapping, allowing 100% of the AVNRT CL to be covered. These results also have clinical implications for the ablation of right-septal and para-septal arrhythmias., (© 2024 Wiley Periodicals LLC.)

Background: Oral prostanoids are recommended in patients with pulmonary arterial hypertension (PAH) and an unsatisfactory response to first-line therapy., Objective: To compare the effectiveness of oral therapies targeting the prostacyclin pathway in PAH patients., Methods: An online search of Medline, Cochrane Registry, Scopus and EMBASE libraries (from inception to May, 12,020) was conducted. Eight randomized controlled studies were included in the meta-analysis involving 3023 patients, with 828 receiving oral treprostinil, 607 patients receiving selexipag, 125 patients receiving beraprost, and 1463 patients receiving placebo., Results: Compared to placebo, oral treprostinil (WMD 9.05, 95% CI 3.0280-15.0839, p = 0.0032) and beraprost (WMD 21.98, 95% CI 5.0536-38.9063, p = 0.0109) were associated with a significant increase in 6-min walking distance (6MWD) at follow-up from baseline, whereas selexipag use was associated with a non-significant increase in 6MWD (WMD 15.41, 95% CI -0.6074; 31.4232, p = 0.0593). Compared to placebo, the risk of clinical worsening was significantly lowered by selexipag (RR 0.47, 95% CI 0.35-0.65, p < 0.001) and oral treprostinil (RR 0.65, 95% CI 0.46-0.90, p 0.012), whereas a non-significant reduction of the outcome was related to beraprost use (RR 0.70, 95% CI 0.36-1.38, p 0.31). No significant difference in 6MWD change and clinical worsening reduction were found among oral treprostinil and selexipag. Beraprost use less frequently caused adverse events as compared to selexipag and oral treprostinil., Conclusions: No differences in 6MWD change, clinical worsening reduction and adverse events rates were found among oral treprostinil and selexipag, resulting in similar efficacy and safety profiles., Competing Interests: Declaration of competing interest R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. The other authors reported no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Aims: The multi-systemic effects of heart failure (HF) resemble the spread observed during cancer. We propose a new score, named HLM, analogous to the TNM classification used in oncology, to assess the prognosis of HF. HLM refers to H: heart damage, L: lung involvement, and M: systemic multiorgan involvement. The aim was to compare the HLM score to the conventional New York Heart Association (NYHA) classification, American College of Cardiology/American Heart Association (ACC/AHA) stages, and left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients., Methods and Results: We performed a multicentre, observational, prospective study of consecutive patients admitted for HF. Heart, lung, and other organ function parameters were collected. Each patient was classified according to the HLM score, NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography. The follow-up period was 12 months. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. A total of 1720 patients who completed the 12 month follow-up period have been enrolled in the study. 520 (30.2%) patients experienced the composite endpoint of all-cause death and rehospitalization due to HF. 540 (31.4%) patients were female. The mean age of the study population was 70.5 ± 12.9. The mean LVEF at admission was 42.5 ± 13%. Regarding the population distribution across the spectrum of HLM score stages, 373 (21.7%) patients were included in the HLM-1, 507 (29.5%) in the HLM-2, 587 (34.1%) in the HLM-3, and 253 (14.7%) in the HLM-4. HLM was the most accurate score to predict the primary endpoint at 12 months. The area under the receiver operating characteristic curve (AUC) was greater for the HLM score compared with the NYHA classification, ACC/AHA stages, or LVEF, regarding the composite endpoint (HLM = 0.645; NYHA = 0.580; ACC/AHA = 0.589; LVEF = 0.572). The AUC of the HLM score was significantly better compared with the LVEF (P = 0.002), ACC/AHA (P = 0.029), and NYHA (P = 0.009) AUC., Conclusions: The HLM score has a greater prognostic power compared with the NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography in terms of the composite endpoint of all-cause death and rehospitalization due to HF at 12 months of follow-up., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction without obstructive coronary artery disease (MINOCA). It is determined by a coronary artery wall layers separation, which occurs regardless of traumatic or iatrogenic injuries. Even if it is often a missed diagnosis, its incidence is growing along with the improvement of intracoronary imaging techniques that allow for better detection. The main angiographical classification distinguishes three different forms, with slightly different prognoses at long-term follow up. SCAD is a recurrent condition, severely hampering the life quality of affected patients. The predominantly young age of patients with SCAD and the high prevalence of females among them have made the topic increasingly important, especially regarding therapeutic strategies. According to the data, the most recommended treatment is conservative, based on the use of antiplatelet agents and supportive anti-ischemic therapy. However, there are conflicting opinions concerning the need for dual antiplatelet therapy and its duration. In the case of invasive treatment, the choice between percutaneous coronary intervention and coronary artery bypass graft depends on the patient's clinical stability and the interested vessel. The purpose of the current review is to revise the pathophysiological mechanisms underlying SCAD and the current knowledge of its treatment.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.

Pediatric cardiomyopathies (CMs) and electrical diseases constitute a heterogeneous spectrum of disorders distinguished by structural and electrical abnormalities in the heart muscle, attributed to a genetic variant. They rank among the main causes of morbidity and mortality in the pediatric population, with an annual incidence of 1.1-1.5 per 100,000 in children under the age of 18. The most common conditions are dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Despite great enthusiasm for research in this field, studies in this population are still limited, and the management and treatment often follow adult recommendations, which have significantly more data on treatment benefits. Although adult and pediatric cardiac diseases share similar morphological and clinical manifestations, their outcomes significantly differ. This review summarizes the latest evidence on genetics, clinical characteristics, management, and updated outcomes of primary pediatric CMs and electrical diseases, including DCM, HCM, arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), and short QT syndrome (SQTS).

Introduction: The efficacy and safety of emerging therapies for heart failure with reduced ejection fraction (HFrEF) have never been compared in specific subgroups of patients., Methods: PubMed, Cochrane Registry, Web of Science, Scopus, and EMBASE libraries were used to extract data. We used the following keywords: (heart failure with reduced ejection fraction OR HFrEF) AND (treatment OR therapy) OR (cardiovascular death) OR (hospitalization for heart failure). We compared randomized clinical trials for HFrEF emerging therapies focusing on the elderly (patients &gt;65 years old and &gt;75 years old), chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) &lt; 60 mL/min), patients with diabetes mellitus (DM), coronary heart disease (CAD), New York Heart Association (NYHA) class III/IV, women, patients on sacubitril/valsartan (S/V). The primary outcome was the efficacy composite endpoint of cardiovascular death (CVD) and HF hospitalization (HFH)., Results: S/V significantly reduced the primary outcome in patients &gt;65 years old (RR: 0.80; 95% CI: 0.68-0.94) and with CKD (RR: 0.79; 95% CI: 0.69-0.90); dapagliflozin in patients &gt;65 (RR: 0.72; 95% CI: 0.60-0.86) and &gt;75 years old (RR: 0.68; 95% CI: 0.53-0.87), in those with CKD (RR: 0.72; 95% CI: 0.59-0.88), DM (RR: 0.75; 95% CI: 0.63-0.89), and CAD (RR: 0.77; 95% CI: 0.65-0.92); empagliflozin in patients &gt;65 years old (RR: 0.78; 95% CI: 0.66-0.93), those with DM (RR: 0.72; 95% CI: 0.60-0.86), CAD (RR: 0.82; 95% CI: 0.68-0.99), women (RR: 0.59; 95% CI: 0.44-0.79), and in patients on S/V (RR: 0.64; 95% CI: 0.45-0.91); vericiguat in patients with CKD (RR: 0.84; 95% CI: 0.73-0.97) and NYHA class III/IV (RR: 0.87; 95% CI: 0.77-0.98); omecamtiv mecarbil in patients with CAD (RR: 0.90; 95% CI: 0.82-0.99) and NYHA III/IV (RR: 0.88; 95% CI: 0.80-0.97)., Conclusion: Emerging HFrEF therapies show a clinical benefit with the reduction of the primary composite endpoint of CVD and HFH, with each drug being more effective in specific patient population., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Oral prostanoids are recommended in patients with pulmonary arterial hypertension (PAH) and a unsatisfactory response to first-line therapy., Objective: To compare effectiveness of oral therapies targeting the prostacyclin pathway in PAH patients., Methods: An online search of Medline, Cochrane Registry, Scopus and EMBASE libraries (from inception to May, 12020) was performed. Eight randomized controlled studies were included in the meta-analysis involving 3023 patients, of whom 828 receiving oral treprostinil, 607 patients receiving selexipag, 125 patients receiving beraprost, and 1463 patients received placebo., Results: As compared to placebo, oral treprostinil (WMD 9.05, 95% CI 3.0280-15.0839, p = 0.0032) and beraprost (WMD 21.98, 95% CI 5.0536-38.9063, p = 0.0109) arms significantly increased 6 min walking distance (6MWD) at follow-up from baseline, whereas selexipag use was associated with a non-significant increase in 6MWD (WMD 15.41, 95% CI -0.6074; 31.4232, p = 0.0593). Compared to placebo, the risk of clinical worsening was significantly lowered by selexipag (RR 0.47, 95% CI 0.35-0.65, p < 0.001) and oral treprostinil (RR 0.65, 95% CI 0.46-0.90, p 0.012), whereas a non-significant reduction of the outcome was related to beraprost use (RR 0.70, 95% CI 0.36-1.38, p 0.31). No significant difference in 6MWD change and clinical worsening reduction were found among oral treprostinil and selexipag. Beraprost use less frequently caused adverse events as compared to selexipag and oral treprostinil., Conclusions: No differences in 6MWD change, clinical worsening reduction and adverse events rates were found among oral treprostinil and selexipag, resulting in similar efficacy and safety profile., (Copyright © 2023. Published by Elsevier B.V.)

Patients with an established diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Despite guideline-directed medical therapy, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF, and patients experiencing WHF carry a substantially higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as arrows in the quiver for clinicians to address the residual risk of HF hospitalization and cardiovascular deaths in patients with WHF. This question-and-answer-based review will discuss the emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC), the new therapeutic approaches to treat WHF and then move on to their timing and safety concerns (i.e., renal profile).

Purpose: The purpose of this review is to explore the benefits and controversies that telemedicine (TM), applied to patients with heart failure (HF), can provide in terms of diagnosis, therapeutic management, and prognosis improvement. During the coronavirus disease 19 (COVID-19) outbreak, TM emerged as the most effective and feasible method available to ensure continuous care for chronic diseases. Among these, HF, characterized by high mortality, morbidity, and the need for frequent visits, may benefit of the TM role. HF patients are affected by frequent exacerbations undergoing a progressive prognosis impoverishment, strongly depending on the disease's management. A precise clinical handling is always required, with a constant optimization of the therapy, a continuous control of risk factors, and a sensitive attention to any change in symptoms, clinical signs, and laboratory tests. In this context, TM has shown to improve therapy adherence and HF: patients' self-care, impacting the prognosis even if specific results are controversial. Major evidence shows that TM may allow an adequate primary prevention, reducing the impact of the main cardiovascular risk factors. TM can also be useful for the secondary prevention, early detecting a likely HF exacerbation before it becomes clinically manifest, thereby lowering the need for hospitalization. Moreover, an optimal up-titration of the therapy and an increase in treatment adherence are feasible by using TM. However, some studies did not show unambiguous results, and uncertainties still remain., (© 2023. The Author(s).)

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high, and diabetes remains the leading cause of end-stage kidney disease in affected patients. To date, current medications for CKD and type 2 diabetes mellitus have not reset residual risk in patients due to a high grade of inflammation and fibrosis contributing to kidney and heart disease. This question-and-answer-based review will discuss the pharmacological and clinical differences between finerenone and other mineralocorticoid receptor antagonists and then move on to the main evidence in the cardiovascular and renal fields, closing, finally, on the potential role of therapeutic combination with sodium-glucose cotransporter 2 inhibitors (SGLT2is).

Heart failure (HF) represents a major health and economic issue, with increasing morbidity and mortality in spite of novel therapeutic weapons. The disappointing results of HF management may be due to the current therapeutic approach based on the paradigm "one fits all", that cannot apply to a complex and multifaceted syndrome as HF. At this regard, the European Union is developing policies to move from reductionism to precision medicine, in order to identify specific disease biomarkers and develop targeted therapeutic strategies. The institution of biobanks may represent the game changer in HF scenario, providing a collection of human biological materials with the related medical and epidemiological data fueling the development of personalized therapeutic approach and fostering current and/or future research projects., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. The other authors reported no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (K ATP ) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215&#95;G/G of KCNJ11 and rs1799983&#95;T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215&#95;G/G of KCNJ11 and rs1799983&#95;T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the K ATP channel that provides a potential protective effect against IHD.

Heart failure (HF) is a major and still growing medical problem and is characterized by episodes of acute decompensation that are associated with a negative prognosis and a significant burden on the patients, doctors, and healthcare resources. Early detection of incipient HF may allow outpatient treatment before patients severely decompensate, thus reducing HF hospitalizations and related costs. The HeartLogic™ algorithm is an automatic, remotely managed system combining data directly related to HF pathophysiology into a single score, the HeartLogic™ index. This index proved to be effective in predicting the risk of incipient HF decompensation, allowing to redistribute resources from low-risk to high-risk patients in a timely and cost-saving manner. The alert-based remote management system seems more efficient than the one based on scheduled remote transmission in terms of caregivers' workload and alert detection timing. The widespread application of the HeartLogic™ algorithm requires the resolution of logistical and financial issues and the adoption of a pre-defined, functional workflow. In this paper, we reviewed general aspects of remote monitoring in HF patients, the functioning and pathophysiological basis of the HeartLogic index, its efficiency in the management of HF patients, and the economic effects and the organizational revolution associated with its use., Competing Interests: Conflict of interest: L.S. has received consultancy fee from Boston Scientific, Abbott Medical and Medtronic., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Ventricular tachycardia in patients with structural heart disease is a significant cause of morbidity and mortality. According to current guidelines, cardioverter defibrillator implantation, antiarrhythmic drugs, and catheter ablation are established therapies in the management of ventricular arrhythmias but their efficacy is limited in some cases. Sustained ventricular tachycardia can be terminated by cardioverter-defibrillator therapies although shocks in particular have been demonstrated to increase mortality and worsen patients' quality of life. Antiarrhythmic drugs have important side effects and relatively low efficacy, while catheter ablation, even if it is actually an established treatment, is an invasive procedure with intrinsic procedural risks and is frequently affected by patients' hemodynamic instability. Stereotactic arrhythmia radioablation for ventricular arrhythmias was developed as bail-out therapy in patients unresponsive to traditional treatments. Radiotherapy has been mainly applied in the oncological field, but new current perspectives have developed in the field of ventricular arrhythmias. Stereotactic arrhythmia radioablation provides an alternative non-invasive and painless therapeutic strategy for the treatment of previously detected cardiac arrhythmic substrate by three-dimensional intracardiac mapping or different tools. Since preliminary experiences have been reported, several retrospective studies, registries, and case reports have been published in the literature. Although, for now, stereotactic arrhythmia radioablation is considered an alternative palliative treatment for patients with refractory ventricular tachycardia and no other therapeutic options, this research field is currently extremely promising.

Background: His- Purkinje system pacing (HPSP) techniques have been proposed as alternative to biventricular pacing (BVP) and right ventricular pacing (RVP)., Objective: To compare data regarding clinical, procedural and lead outcomes associated with different pacing techniques., Methods: An accurate search of online scientific libraries (from inception to May, 12,022) was performed. Thirty-three studies were included in the meta-analysis involving 4386 patients, of whom 1324 receiving RVP, 1032 patients receiving BVP, 1069 patients receiving his-bundle pacing (HBP) and 968 patients receiving left bundle branch pacing (LBBP)., Results: LBBP provided a statistically significant increase in LVEF relative to HBP (0.4473 [0.0584; 0.8361] p = 0.0242) and BVP (0.6733 [0.4734; 0.8732] p < 0.0001) in patients with cardiac resynchronization therapy indication. LBBP and HBP significantly decreased QRS duration as compared to BVP, with largest QRS narrowing obtained by LBBP (-0.4951 [-0.9077; -0.0824] p = 0.0187). As compared to LBBP, HBP was associated with a significant increase of pacing threshold (p = 0.0369) and significant reduction of R-wave amplitude over time (p = 0.027). LBBP was associated with significant reduction in RR of hospitalization for HF (HFH) as compared to both BVP (p = 0.0343) and HBP (p = 0.0476), whereas, as compared to RVP, the risk of lead issues was significantly higher with BVP (p = 0.0424) and HBP (p = 0.0298), but not for LBBP (p = 0.425)., Conclusions: As compared to other pacing techniques, LBBP significantly improved LVEF, narrowed QRS duration and reduced HFHs, with steadily lower capture thresholds and higher R-wave amplitude, and without increasing lead issues., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. This research did not receive any specific grant from founding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The feasibility and effectiveness of virtual visits (VVs) for cardiac electrophysiology patients are still unknown. We aimed to assess the feasibility and effectiveness of VVs as compared to in-person visits, and to describe patient experience with virtual care in clinical electrophysiology. We prospectively enrolled patients scheduled to receive a clinical electrophysiology evaluation, dividing them in two groups: a VV group and an in-person visit group. Outcomes of interest were: (1) improvement in symptoms after the index visit, (2) disappearance of remote monitoring (RM) alerts at follow-up, (3) necessity of urgent hospitalization and (4) patient satisfaction measured by the Patient Satisfaction Questionnaire-18 (PSQ-18). This study included 162 patients in the VV group and 185 in the in-office visit group. As compared to in-person visits, VVs resulted in a similar reduction in RM alerts (51.5% vs. 43.2%, p-value 0.527) and in symptomatic patient rates (73.6% vs. 56.9%, p-value 0.073) at follow-up, without differences in urgent hospitalization rates (p-value 0.849). Patient satisfaction with VVs was higher than with in-person evaluation (p-value < 0.012). VVs proved to be as feasible and as effective as in-person visits, with high patient satisfaction. A hybrid model of care including VVs and in-person visits may become the new standard of care after the COVID-19 pandemic is over.

Background: Arrhythmic death is very common among patients with structural heart disease, and it is estimated that in European countries, 1 per 1000 inhabitants yearly dies for sudden cardiac death (SCD), mainly as a result of ventricular arrhythmias (VA). The scar is the result of cardiac remodelling process that occurs in several cardiomyopathies, both ischemic and non-ischemic, and is considered the perfect substrate for re-entrant and non-re-entrant arrhythmias., Methods: Our aim was to review published evidence on the histological and electrophysiological properties of myocardial scar and to review the central role of cardiac magnetic resonance (CMR) in assessing ventricular arrhythmias substrate and its potential implication in risk stratification of SCD., Results: Scarring process affects both structural and electrical myocardial properties and paves the background for enhanced arrhythmogenicity. Non-uniform anisotropic conduction, gap junctions remodelling, source to sink mismatch and refractoriness dispersion are some of the underlining mechanisms contributing to arrhythmic potential of the scar. All these mechanisms lead to the initiation and maintenance of VA. CMR has a crucial role in the evaluation of patients suffering from VA, as it is considered the gold standard imaging test for scar characterization. Mounting evidences support the use of CMR not only for the definition of gross scar features, as size, localization and transmurality, but also for the identification of possible conducting channels suitable of discrete ablation. Moreover, several studies call out the CMR-based scar characterization as a stratification tool useful in selecting patients at risk of SCD and amenable to implantable cardioverter-defibrillator (ICD) implantation., Conclusions: Scar represents the substrate of ventricular arrhythmias. CMR, defining scar presence and its features, may be a useful tool for guiding ablation procedures and for identifying patients at risk of SCD amenable to ICD therapy., (© 2022. The Author(s).)

Atrial fibrillation (AF) is the most frequent chronic arrhythmia worldwide, and it is associated with significant morbidity and mortality, making it a considerable burden both to patients and the healthcare system. Nowadays, an early attempt to restore sinus rhythm in acute symptomatic AF through electrical or pharmacological cardioversion is the most common approach in the Emergency Department (ED). However, considering the high percentage of spontaneous cardioversion of paroxysmal AF reported by many studies, this approach may not be the ideal choice for all patients. In this manuscript we performed a review of the most relevant studies found in literature with the aim of identifying the main determinants of spontaneous cardioversion, focusing on those easy to detect in the ED. We have found that the most relevant predictors of spontaneous cardioversion are the absence of Heart Failure (HF), a small atrial size, recent-onset AF, rapid Atrial Fibrillatory Rate and the relationship between a previous AF episode and Heart Rate/Blood Pressure. A number of those are utilized, along with other easily determined parameters, in the recently developed "ReSinus" score which predicts the likelihood of AF spontaneous cardioversion. Such identification may help the physician decide whether immediate cardioversion is necessary, or whether to adopt a "watch-and-wait" strategy in the presence of spontaneous cardioversion determinants., Competing Interests: The authors declare no conflict of interest.

Background: COVID-19 pandemic severely affected national health systems, altering the modality and the type of care of patients with acute and chronic diseases. To minimize the risk of exposure to SARS-CoV2 for patients and health professionals, face-to-face visits were cancelled or postponed and the use of telemedicine was strongly encouraged. This reorganization involved especially patients with rare diseases needing periodic comprehensive assessment, such as pulmonary arterial hypertension (PAH)., Main Body: The paper reports a proposal of strategy adopted for patients followed at our PAH center in Rome, where patients management was diversified based on clinical risk according to the European Society of Cardiology/European Respiratory Society PH guidelines-derived score and the REVEAL 2.0 score. A close monitoring and support of these patients were made possible by policy changes reducing barriers to telehealth access and promoting the use of telemedicine. Synchronous/asynchronous modalities and remote monitoring were used to collect and transfer medical data in order to guide physicians in therapeutic-decision making. Conversely, the use of implantable monitors providing hemodynamic information and echocardiography-mobile devices wirelessly connecting was limited by the poor experience existing in this setting. Large surveys and clinical trials are welcome to test the potential benefit of the optimal balance between traditional PAH management and telemedicine opportunities., Conclusion: Italy was found unprepared to manage the dramatic effects caused by COVID-19 on healthcare systems. In this emergency situation telemedicine represented a promising tool especially in rare diseases as PAH, but was limited by its scattered availability and legal and ethical issues. Cohesive partnership of health care providers with regional public health officials is needed to prioritize PAH patients for telemedicine by dedicated tools., Competing Interests: Declaration of Competing Interest R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. The other authors reported no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making., Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario., Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017-2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI)., Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs., Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

The burden of cardiovascular comorbid conditions was significantly higher in patients with atrial fibrillation (AF); most of them are affected by hypertension, chronic kidney disease (CKD) and/or diabetes mellitus (DM). DM represents a well-known risk factor for the development and maintenance of AF; the coexistence of DM and AF is also associated with an increased risk of mortality and stroke. Moreover, DM is currently the main cause of renal impairment and the leading cause of dialysis in the world. The hyperglycemia is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease. Long-term thromboembolic preventive therapy in AF patients with DM and CKD may be more challenging because both DM and CKD have been independently associated with an increased thromboembolic and bleeding risk, which results from the prothrombotic and proinflammatory status. Vitamin K antagonists (VKAs) are characterized by numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. On the other hand, Direct Oral Anticoagulants (DOACs) are currently contraindicated in dialysis patients even if mounting evidence suggests that they may have a nephroprotective role in AF patients with DM and CKD. Consequently, the choice of anticoagulant therapy in this setting of patient seems to be very challenging. The aim of this review is to investigate the role of DOACs in diabetic patients and its nephroprotective role by reviewing the current literature.

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., (© 2022. The Author(s).)

Background: Effects of Sacubitril/Valsartan (S/V) on left ventricular (LV) mechanics and ventricular-arterial coupling in patients with heart failure with reduced ejection fraction (HFrEF) are not completely understood. The aim of this study was to evaluate both cardiac and vascular remodeling in a group of HFrEF patients undergoing S/V therapy., Methods: Fifty HFrEF patients eligible to start a therapy with S/V were enrolled. Echocardiographic evaluation was performed at baseline and after 6 months of follow-up (FU). Beside standard evaluation, including global longitudinal strain (GLS), estimated hemodynamic forces (HDFs) and non-invasive pressure-volume curves (PV loop) were assessed using dedicated softwares. HDFs were evaluated over the entire cardiac cycle, in systole and diastole, both in apex to base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs was evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio). Parameters derived from estimated PV loop curves were left ventricular end-systolic elastance (E es ), arterial elastance (E a ), and ventricular-arterial coupling (VAC)., Results: At 6 months of FU indexed left ventricular end-diastolic and end-systolic volumes decreased (EDVi: 101 ± 28 mL vs. 86 ± 30 mL, p < 0.001; ESVi: 72 ± 23 mL vs. 55 ± 24 mL, p < 0.001), ejection fraction and GLS significantly improved (EF: 29 ± 6% vs. 37 ± 7%, p < 0.001; GLS: -9 ± 3% vs. -13 ± 4%, p < 0.001). A reduction of E a (2.11 ± 0.91 mmHg/mL vs. 1.72 ± 0.44 mmHg/mL, p = 0.008) and an improvement of E es (1.01 ± 0.37 mmHg/mL vs. 1.35 ± 0.6 mmHg/mL, p < 0.001) and VAC (2.3 ± 1.1 vs. 1.5 ± 0.7, p < 0.001) were observed. Re-alignment of HDFs occurred, with a reduction of diastolic L-S/A-B HDFs ratio [23 (20-35)% vs. 20 (11-28) %, p < 0.001]., Conclusion: S/V therapy leads to a complex phenomenon of reverse remodeling involving increased myocardial contractility, HDFs distribution improvement, and afterload reduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Monosilio, Filomena, Luongo, Sannino, Cimino, Neccia, Mariani, Birtolo, Benedetti, Tonti, Pedrizzetti, Vizza, Maestrini and Agati.)

Background: Catheter ablation of papillary muscle ventricular arrhythmias (PM-VAs) has been associated with unsatisfactory results. Features that may affect acute and long-term procedural outcomes are not well established., Objective: To systematically review the available data in the literature assessing efficacy and safety of PM-VAs catheter ablation., Methods: An online search of PubMed, Cochrane Registry, Web of Science, Scopus and EMBASE libraries (from inception to March 1, 2021) was performed, in addition to manual screening. Twenty-one observational noncontrolled case-series were considered eligible for the systematic review, including 536 patients., Results: Postero-medial PM harbored 60.8% of PM-VAs, while antero-lateral PM and right ventricular PMs 34.9% and 4.3% of cases, respectively. The mean acute success rate of the index ablation procedure was 88.1% (95% CI 82.8% to 91.9%, p < .001, I 2 0%). After a mean follow-up period of 15.5 ± 17.4 months, pooled long-term arrhythmia-free rate was 69.2%, while the pooled long-term success rate after multiple ablation procedure was 84.9%. Overall, procedure complications occurred in nine patients (1.7%) and no procedure-related deaths were reported. The use of intracardiac echocardiography (ICE) as well as contact force sensing (CFS) and irrigated catheters during ablation was associated with higher rates of arrhythmia-freedom at long-term follow-up., Conclusions: Catheter ablation is an effective and safe strategy for PM-VAs, with an acute success rate of 88.1%, a long-term success rate of 69.2%, with a relatively low procedural complication rate. The use of ICE, irrigated catheters and catheters with CFS capability was associated with higher rates of arrhythmia-freedom at long-term follow-up., (© 2022 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

During the coronavirus disease 2019 (COVID-19) worldwide pandemic, patients with cardiac implantable electronic device (CIED) refused scheduled follow-up visits because of the risk of infection. In this scenario, different telemedicine strategies have been implemented to ensure continuity of care to CIED patients. Patients can be monitored through dedicated applications, telephone calls, or virtual visits providing easy access to valuable information, such as arrhythmic events, acute decompensation manifestations, and device-related issues, without the need for in-person visits. This review provides a comprehensive description of the many possible applications of telemedicine for CIED patients during the COVID-19 period., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Noncompaction cardiomyopathy (NCCM) is a rare condition characterized by prominent trabeculae, deep intertrabecular recesses, and a left ventricular myocardium with a two-layered structure, characterized by a spongy endocardial layer and a thinner and compacted epicardial one. NCCM can be isolated or associated with other congenital heart diseases and complex syndromes involving neuromuscular disorders and facial dysmorphisms. To date, more than 40 genes coding for sarcomeric, cytoskeletal, ion channels, and desmosomal proteins have been identified. Clinical presentation is also highly variable, ranging from no symptoms to end-stage heart failure (HF), lethal arrhythmias, sudden cardiac death, or thromboembolic events. In particular, the prevalence of thromboembolism in NCCM patients appears to be higher than that of a similar, age-matched population without NCCM. Thromboembolism has a multifactorial aetiology, which is linked to genetic, as well as traditional cardiovascular risk factors. In previous studies, atrial fibrillation (AF) was observed in approximately 25-30% of adult NCCM patients and embolism had a cardiac source in ~63-69% of cases; therefore, AF represents a strong predictor of adverse events, especially if associated to HF and neuromuscular disorders. Left ventricular dysfunction is another risk factor for thromboembolism, as a result of blood stagnation and local myocardial injury. Moreover, it is not completely clarified if the presence of deep intertrabecular recesses causing stagnant blood flow can constitute per se a thrombogenic substrate even in absence of ventricular dysfunction. For the clinical management of NCCM patients, an appropriate stratification of the thromboembolic risk is of utmost importance for a timely initiation of anticoagulant therapy. The aim of the present study is to review the available literature on NCCM with particular attention on thromboembolic risk stratification and prevention and the current evidence for oral anticoagulation therapy. The use of direct oral anticoagulants vs. vitamin K antagonists is also discussed with important implications for patient treatment and prognosis., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The frequent coexistence in daily clinical practice of chronic kidney disease (CKD) and atrial fibrillation (AF), especially in the elderly, represents a conundrum for physicians, mainly related to the management of anticoagulant therapy. The reduction of estimated glomerular filtration rate (eGFR) impairs anticoagulant clearance, increasing bleeding propensity. Moreover, dysfunctional responses of endothelial cells and inflammatory systems both trigger thromboembolic status. Those mechanisms pose an increased risk of adverse events for AF patients with CKD. While several data suggested the use of direct oral anticoagulants (DOACs) over warfarin as preferred anticoagulant strategy in patients with Stage 3A to Stage 4 CKD (eGFR range of 15-49 mL/min/1.73 m2), less is known about the optimal anticoagulation management in patients with end-stage renal disease (ESRD) or on renal replacement therapy (RRT). Furthermore, a pivotal feature to be considered when choosing the anticoagulant drug in CKD patients is represented by nephroprotective capability. Indeed, anticoagulant therapy with warfarin showed detrimental effects on kidney function, whereas DOACs demonstrated a beneficial effect on renal function preservation. Mounting data showed that, when pharmacological treatment cannot be pursued due to contraindication to anticoagulation, left atrial appendage occlusion (LAAO) may represent a valid alternative. This brief review outlines the current knowledge regarding anticoagulation therapy in ESRD/RRT patients, reporting new lines of evidence on the nephroprotective effect of oral anticoagulants and on the use of LAAO as a non-pharmacological alternative to oral anticoagulation., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Precision medicine, providing the right therapeutic strategy for the right patient, could revolutionize management and prognosis of patients affected by cardiovascular diseases. Big data and artificial intelligence are pivotal for the realization of this ambitious design. In the setting of pulmonary arterial hypertension (PAH), the use of computational models and data derived from ambulatory implantable hemodynamic monitors could provide useful information for tailored treatment, as requested by precision medicine.

Background: Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b - 4., Methods: This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b - 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months., Results: Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value <0.001)., Conclusions: Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function., (Copyright © 2021 Elsevier B.V. All rights reserved.)