Physical exercise in hypertensive heart disease: From the differential diagnosis to the complementary role of exercise.

Arterial hypertension (AH) is one of the most common pathologic conditions and represents an important cardiovascular risk factor. Uncontrolled AH is a leading risk factor for cardiovascular disease and mortality. AH chronically causes myocardial and arterial remodelling with hemodynamic changes affecting the heart and other organs, with potentially irreversible consequences leading to poor outcomes. Therefore, a proper and early treatment of AH is crucial after the diagnosis. Beyond medical treatment, physical exercise also plays a therapeutic role in reducing blood pressure, given its potential effects on sympathetic tone, renin-angiotensin-aldosterone system, and endothelial function. International scientific societies recommend physical exercise among lifestyle modifications to treat AH in the first stages of the disease. Moreover, some studies have also shown its usefulness in addition to drugs to reduce blood pressure further. Therefore, an accurate, personalized exercise prescription is recommended to optimize the prevention and treatment of hypertension. On the other hand, uncontrolled AH in athletes requires proper risk stratification and careful evaluation to practice competitive sports safely. Moreover, the differential diagnosis between hypertensive heart disease and athlete's heart is sometimes challenging and requires a careful and comprehensive interpretation in order not to misinterpret the clinical findings. The present review aims to discuss the relationship between hypertensive heart disease and physical exercise, from diagnostic tools to prevention and treatment strategies.

Evolocumab Treatment in Dyslipidemic Patients Undergoing Coronary Artery Bypass Grafting: One-Year Safety and Efficacy Results.

Background: The inhibition of PCSK9 lowered LDL cholesterol levels, reducing the risk of cardiovascular events. However, the effect on patients who have undergone surgical myocardial revascularization has not yet been evaluated. Methods: From January 2017 to December 2022, 180 dyslipidemic patients who underwent coronary artery bypass were included in the study. Until December 2019, 100 patients optimized therapy with statin ± ezetimibe (SG). Since January 2020, 80 matched patients added treatment with Evolocumab every 2 weeks (EG). All 180 patients were followed-up at 3 and 12 months, comparing outcomes. Results: The two groups are homogenous. At 3 months and 1 year, a significant decrease in the parameter mean levels of LDL cholesterol and total cholesterol is detected in the Evolocumab group compared to the standard group. No mortality was detected in either group. No complications or drug discontinuation were recorded. In the SG group, five patients (5%) suffered a myocardial infarction during the 1-year follow-up. In the EG group, two patients (2.5%) underwent PTCA due to myocardial infarction. There is no significant difference in overall survival according to the new treatment (p-value = 0.9), and the hazard ratio is equal to 0.94 (95% C.I.: [0.16-5.43]; p-value = 0.9397). Conclusions: The use of Evolocumab, which was started immediately after coronary artery bypass graft surgery, significantly reduced LDL cholesterol and total cholesterol levels compared to statin treatment alone and is completely safe. However, at one year of follow-up, this result did not have impact on the reduction in major clinical events.

The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods.

Histone deacetylases (HDACs) are crucial in gene transcription, removing acetyl groups from histones. They also influence the deacetylation of non-histone proteins, contributing to the regulation of various biological processes. Thus, HDACs play pivotal roles in various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions, highlighting their potential as therapeutic targets. This paper reviews the structure and function of the four classes of human HDACs. While four HDAC inhibitors are currently available for treating hematological malignancies, numerous others are undergoing clinical trials. However, their non-selective toxicity necessitates ongoing research into safer and more efficient class-selective or isoform-selective inhibitors. Computational methods have aided the discovery of HDAC inhibitors with the desired potency and/or selectivity. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, three-dimensional quantitative structure-activity relationships, and structure-based virtual screening (molecular docking). Moreover, recent developments in the field of molecular dynamics simulations, combined with Poisson-Boltzmann/molecular mechanics generalized Born surface area techniques, have improved the prediction of ligand binding affinity. In this review, we delve into the ways in which these methods have contributed to designing and identifying HDAC inhibitors.

Arrhythmic Mitral Valve Prolapse and Sports Activity: Pathophysiology, Risk Stratification, and Sports Eligibility Assessment.

Although mitral valve prolapse (MVP) is the most prevalent valvular abnormality in Western countries and generally carries a good prognosis, a small subset of patients is exposed to a significant risk of malignant ventricular arrhythmias (VAs) and sudden cardiac death (SCD), the so-called arrhythmic MVP (AMVP) syndrome. Recent work has emphasized phenotypical risk features of severe AMVP and clarified its pathophysiology. However, the appropriate assessment and risk stratification of patients with suspected AMVP remains a clinical conundrum, with the possibility of both overestimating and underestimating the risk of malignant VAs, with the inappropriate use of advanced imaging and invasive electrophysiology study on one hand, and the catastrophic occurrence of SCD on the other. Furthermore, the sports eligibility assessment of athletes with AMVP remains ill defined, especially in the grey zone of intermediate arrhythmic risk. The definition, epidemiology, pathophysiology, risk stratification, and treatment of AMVP are covered in the present review. Considering recent guidelines and expert consensus statements, we propose a comprehensive pathway to facilitate appropriate counseling concerning the practice of competitive/leisure-time sports, envisioning shared decision making and the multidisciplinary "sports heart team" evaluation of borderline cases. Our final aim is to encourage an active lifestyle without compromising patients' safety.

Idiopathic Premature Ventricular Contraction Catheter Ablation, Sedentary Population vs. Athlete's Populations: Outcomes and Resumption of Sports Activity.

There are no investigations about the outcomes of idiopathic PVC catheter ablation (CA) in athletes compared to the sedentary population. We conducted a prospective single-centre observational study. The primary and secondary procedural outcomes were the post-ablation reduction of premature ventricular contractions (PVCs) in an athletes vs. non-athletes group and in agonist vs. leisure-time athletes. The third was the evaluation of the resumption of physical activity and the improvement of symptoms in agonist and leisure-time athletes. From January 2020 to October 2022 we enrolled 79 patients with RVOT/LVOT/fascicular PVC presumed origin. The median percentage of decrease between the pre-procedure and post-procedure Holter monitoring in the non-athletes group was 96 (IQR 68-98) and 98 in the athletes group (IQR 92-99) (p = 0.08). Considering the athletes, the median percentage of decrease in the number of PVCs was 98 (IQR 93-99) and 98 (IQR 87-99), respectively, in leisure-time and agonistic athletes (p = 0.42). Sixteen (70%) leisure time and seventeen (90%) agonist athletes (p = 0.24) have resumed physical activity 3 months after PVC CA; among agonistic athletes, 59% have resumed competitive physical activity. Many leisure-time (88%) and agonist (70%) athletes experienced an improvement in symptoms after ablation. PVC CA was effective and safe in both groups, reducing symptoms and allowing a quick and safe return to sports activities in athletes.

Pathophysiology of Atrial Fibrillation and Approach to Therapy in Subjects Less than 60 Years Old.

Atrial fibrillation (AF) is an arrhythmia that affects the left atrium, cardiac function, and the patients' survival rate. Due to empowered diagnostics, it has become increasingly recognized among young individuals as well, in whom it is influenced by a complex interplay of autoimmune, inflammatory, and electrophysiological mechanisms. Deepening our understanding of these mechanisms could contribute to improving AF management and treatment. Inflammation is a complexly regulated process, with interactions among various immune cell types, signaling molecules, and complement components. Addressing circulating antibodies and designing specific autoantibodies are promising therapeutic options. In cardiomyopathies or channelopathies, the first manifestation could be paroxysmal AF; persistent forms tend not to respond to antiarrhythmic drugs in these conditions. Further research, both in vitro and in vivo, on the use of genomic biotechnology could lead to new therapeutic approaches. Additional triggers that can be encountered in AF patients below 60 years of age are systemic hypertension, overweight, diabetes, and alcohol abuse. The aims of this review are to briefly report evidence from basic science and results of clinical studies that might explain the juvenile burden of the most encountered sustained supraventricular tachyarrhythmias in the general population.

COMPArison of Multi-Point Pacing and ConvenTional Cardiac Resynchronization Therapy Through Noninvasive Hemodynamics Measurement: Short- and Long-Term Results of the COMPACT-MPP Study.

Invasive hemodynamic studies have shown improved left ventricular (LV) performances when cardiac resynchronization therapy/defibrillator is delivered through multipoint pacing (MPP). Nowadays, strategies have become available that allow studying the same hemodynamic parameters at a noninvasive level. The aim of the present study was to evaluate the clinical implication of using a patient-tailored approach for cardiac resynchronization therapy programming based on noninvasively assessed LV hemodynamics to identify the best biventricular pacing modality between standard single-site pacing (STD) and MPP for each patient. Therefore, 51 patients with heart failure (age 69 ± 9 years, 35 men, 27% ischemic etiology) implanted with cardiac resynchronization therapy/defibrillator underwent noninvasive LV function assessment through photoplethysmography before hospital discharge for addressing dP/dt and stroke volume in both pacing modalities (STD and MPP). The modality that performed better in terms of hemodynamic improvement was permanently programmed. Global longitudinal strain (GLS) was also assessed, and repeated at 3 months. Compared with intrinsic rhythm (928 ± 486 mm Hg/s), dP/dtmax showed a trend to increase in both biventricular pacing modes (1,000 ± 577 mm Hg/s in STD, 1,036 ± 530 mm Hg/s in MPP, p = NS). MPP was associated with a wider hemodynamic improvement than was STD and was the modality of choice in 34 of 51 patients (67%). GLS at predischarge did not differ between groups (-10.3 ± 3.8% vs -10.2 ± 3.5%), but significant improvement of ejection fraction at 1 month (34.4 ± 5.3%, p <0.001) and of GLS at 3 months (-12.9 ± 2.9%, p <0.005) was observed across the entire cohort. At 3 months, 77% of patients were classified as responders. Interestingly, long-term (3 years) follow-up unveiled a reduction in all-cause mortality in the MPP group compared with the STD group. In conclusion, cardiac resynchronization therapy programming guided by acute noninvasive hemodynamics favored MPP modality and caused short-term LV positive remodeling and improved long-term outcomes. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT04299360.

Cardiovascular Prognosis in Patients with Peripheral Artery Disease and Approach to Therapy.

Peripheral artery disease (PAD), the pathophysiologic narrowing of the arterial blood vessels of the lower limbs due to atherosclerosis, is estimated to affect more than 200 million people worldwide and its prevalence ranges from 0.9 to 31.3% in people aged ≥50 years. It is an established marker of systemic obstructive atherosclerosis, which depicts patients at higher risk of myocardial infarction and stroke, due to the involvement of coronary and cerebral arteries in the atherosclerotic process. Therefore, identifying PAD, particularly in patients with coronary artery disease, is important to assess the cardiovascular risk score and implement specific therapies and prevention strategies. Since PAD emerged as an important clinical cardiovascular predictor, even more than other typical cardiovascular risk factors, an aggressive strategy to identify and treat PAD patients should be pursued by general practitioners, cardiologists, and vascular surgeons; similarly, preventive strategies should be implemented to improve prognosis and outcomes, particularly in patients suffering from both coronary artery disease and PAD. In this review, we describe the pathophysiology, including limb vasoconstriction after coronary angioplasty, the diagnosis of PAD, prognosis according to cardiovascular events, coronary artery disease, and heart failure. Furthermore, a large section of this review is on management, which spans from risk factors' modification to antithrombotic therapy, and revascularization is provided. Finally, considerations about newer therapeutic options for the "desert foot" are discussed, including gene therapy.

Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers.

Cardiac myxoma (CM) is a potentially life-threatening disease because frequently asymptomatic or debuts with aspecific manifestations. Definitive diagnosis is established by histopathological assessment including tumor and endothelial cell markers. To derive a specific panel of circulating cells antigenically detectable, pre-surgery peripheral blood samples of CM patients were analyzed. Pre-surgery peripheral blood samples from patients with CM were simultaneously analyzed for Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) that were matched with tumor tissue profiles and with patient-derived xenografts (PDXs) distinguishing tumor regions. Moreover, CECs values in CM patients were further matched with CEC's levels in cardiovascular disease and control subjects. The blood-derived cytological specimens detected at least 1-3 CTCs/ml in 10 tested CM samples (p = 0.0001) showing specific CM features preserved in the central zones of the tumor. The central zone of the primary tumor, supported by a vessel density rate (55 ± 7%), with a proliferative profile of 32 ± 3% and a percentage of Calretininpos cells (p = 0.03), is the principal site of CTCs (r = 00) dissemination. The subsets of endothelial cells recognized in the blood were indifferent to their topological distribution within the tumor and corresponding PDXs. With further refinement and validation in large cohorts, multiparametric liquid biopsies can optimally integrate clinically informative datasets and maximize their utility in pre-surgery evaluation of CM patients. Blood-derived culture's protocol provides a versatile method capable of viable analysis of CTCs of non-hematological rare tumors which conventional antibody-mediated analytical platform is unable to perform. Distinctive blood- based cell phenotype contributes to differentiate CM from other differentials assuring its prompt surgical resection by combining blood-based cell biomarkers integrated with clinically informative datasets.

Integration of a Smartphone HF-Dedicated App in the Remote Monitoring of Heart Failure Patients with Cardiac Implantable Electronic Devices: Patient Access, Acceptance, and Adherence to Use.

(200 w) Introduction. Remote monitoring (RM) of cardiac implantable electronic device (CIED) diagnostics helps to identify patients potentially at risk of worsening heart failure (HF). Additionally, knowledge of patient HF-related symptoms is crucial for decision making. Patient smartphone applications may represent an ideal option to remotely collect this information. PURPOSE: To assess real-world HF patient access, acceptance, and adherence to use of an HF-dedicated smartphone application (HF app). METHODS: In this study, 10 Italian hospitals administered a survey on smartphone/app use to HF patients with CIED. The subgroup who accepted it downloaded the HF app. Mean 1-year adherence of the HF app use was evaluated. RESULTS: A total of 495 patients (67 ± 13 years, 79% males, 26% NYHA III-IV) completed the survey, of which 84% had access to smartphones and 85% were willing to use the HF app. In total, 311/495 (63%) downloaded the HF app. Patients who downloaded the HF app were younger and had higher school qualification. Patients who were ≥60 years old had higher mean 1-year adherence (54.1%) than their younger counterparts (42.7%; p < 0.001). Hospitals with RM-dedicated staff had higher mean 1-year patient adherence (64.0% vs. 33.5%; p < 0.001). Adherence to HF app decreased from 63.3% (weeks_1-13) to 42.2% (weeks_40-52, p < 0.001). CONCLUSIONS: High access and acceptance of smartphones/apps by HF patients with CIED allow HF app use for RM of patient signs/symptoms. Younger patients with higher school qualifications are more likely to accept HF app; however, older patients have higher long-term adherence.

Revascularization and Left Ventricular Dysfunction for ICD Eligibility.

Common triggers for sudden cardiac death (SCD) are transient ischemia, hemodynamic fluctuations, neurocardiovascular influences, and environmental factors. SCD occurs rapidly when sinus rhythm degenerates into ventricular tachycardia (VT) and/or ventricular fibrillation (VF), followed by asystole. Such progressive worsening of the cardiac rhythm is in most cases observed in the setting of ischemic heart disease and often associated with advanced left ventricular (LV) impairment. Revascularization prevents negative outcomes including SCD and heart failure (HF) due to LV dysfunction (LVD). The implantable cardioverter-defibrillator (ICD) on top of medical therapy is superior to antiarrhythmic drugs for patients with LVD and VT/VF. The beneficial effects of ICD have been demonstrated in primary prevention of SCD as well. However, yet debated is the temporal management for patients with LVD who are eligible to ICD prior to revascularization, either through percutaneous or surgical approach. Restoration of coronary blood flow has a dramatic impact on adverse LV remodeling, while it requires aggressive long-term antiplatelet therapy, which might increase complication for eventual ICD procedure when percutaneous strategy is pursued; on the other hand, when LV and/or multiorgan dysfunction is present and coronary artery bypass grafting is chosen, the overall risk is augmented, mostly in HF patients. The aims of this review are to describe the pathophysiologic benefits of revascularization, the studies addressing percutaneous, surgical or no revascularization and ICD implantation, as well as emerging defibrillation strategies for patients deemed at transient risk of SCD and/or at higher risk for transvenous ICD implantation.

Impact of Percutaneous Mitral Valve Repair on Left Atrial Strain and Atrial Fibrillation Progression.

Transcatheter edge-to-edge repair (TEER) currently represents a valuable therapeutic option for patients with severe mitral regurgitation (MR) considered at high surgical risk. Besides symptoms and left ventricular (LV) echocardiographic improvements upon TEER, it has been postulated that left atrial (LA) function plays a prognostic role. The aims of our study were to evaluate LA changes after TEER, measured by two-dimensional speckle-tracking echocardiography analysis (2D-STE), their association with atrial fibrillation (AF) occurrence, and relative arrhythmic burden. We considered in a single-center study 109 patients affected by symptomatic severe MR undergoing TEER from February 2015 to April 2022. By 2D-STE, LA reservoir (R_s), conduct (D_s), and contractile (C_s) strains were assessed along with four-chamber emptying fraction (LAEF-4CH) before, 1, 6, and 12 months following TEER. Statistical analysis for comparison among baseline, and follow-ups after TEER was carried out by ANOVA, MANOVA, and linear regression. Successful TEER significantly improved LV dimensions and LA performances, as indicated by all strain components, and LAEF-4CH after 1 year. Strikingly, a significant reduction in arrhythmic burden was observed, since only one case of subclinical AF detected by a previously implanted cardiac electronic device was found in the cohort of sinus rhythm patients (n = 48) undergone TEER; in addition, ventricular rate was reduced in the AF cohort (n = 61) compared to baseline, together with few episodes of nonsustained ventricular tachycardias (5/61, 8.2%) after MR improvement. Overall, TEER was associated with improved cardiac performance, LA function amelioration, and reduced arrhythmic burden.

Modern subcutaneous implantable defibrillator therapy in patients with cardiomyopathies and channelopathies: data from a large multicentre registry.

AIMS: Patients with cardiomyopathies and channelopathies are usually younger and have a predominantly arrhythmia-related prognosis; they have nearly normal life expectancy thanks to the protection against sudden cardiac death provided by the implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) is an effective alternative to the transvenous ICD and has evolved over the years. This study aimed to evaluate the rate of inappropriate shocks (IS), appropriate therapies, and device-related complications in patients with cardiomyopathies and channelopathies who underwent modern S-ICD implantation. METHODS AND RESULTS: We enrolled consecutive patients with cardiomyopathies and channelopathies who had undergone implantation of a modern S-ICD from January 2016 to December 2020 and who were followed up until December 2022. A total of 1338 S-ICD implantations were performed within the observation period. Of these patients, 628 had cardiomyopathies or channelopathies. The rate of IS at 12 months was 4.6% [95% confidence interval (CI): 2.8-6.9] in patients with cardiomyopathies and 1.1% (95% CI: 0.1-3.8) in patients with channelopathies (P = 0.032). No significant differences were noted over a median follow-up of 43 months [hazard ratio (HR): 0.76; 95% CI: 0.45-1.31; P = 0.351]. The rate of appropriate shocks at 12 months was 2.3% (95% CI: 1.1-4.1) in patients with cardiomyopathies and 2.1% (95% CI: 0.6-5.3) in patients with channelopathies (P = 1.0). The rate of device-related complications was 0.9% (95% CI: 0.3-2.3) and 3.2% (95% CI: 1.2-6.8), respectively (P = 0.074). No significant differences were noted over the entire follow-up. The need for pacing was low, occurring in 0.8% of patients. CONCLUSION: Modern S-ICDs may be a valuable alternative to transvenous ICDs in patients with cardiomyopathies and channelopathies. Our findings suggest that modern S-ICD therapy carries a low rate of IS. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/Identifier: NCT02275637.

Drug management of atrial fibrillation in light of guidelines and current evidence: an Italian Survey on behalf of Italian Association of Arrhythmology and Cardiac Pacing.

AIM: Atrial fibrillation is a multifaceted disease requiring personalized treatment, in accordance with current ESC guidelines. Despite a wide range of literature, we still have various aspects dividing the opinion of the experts in rate control, rhythm control and thromboembolic prophylaxis. The aim of this survey was to provide a country-wide picture of current practice regarding atrial fibrillation pharmacological management according to a patient's characteristics. METHODS: Data were collected using an in-person survey that was administered to members of the Italian Association of Arrhythmology and Cardiac Pacing. RESULTS: We collected data from 106 physicians, working in 72 Italian hospitals from 15 of 21 regions. Our work evidenced a high inhomogeneity in atrial fibrillation management regarding rhythm control, rate control and thromboembolic prophylaxis in both acute and chronic patients. This element was more pronounced in settings in which literature shows a lack of evidence and, consequently, the indications provided by the guidelines are weak or absent. CONCLUSION: This National survey evidenced a high inhomogeneity in current approaches adopted for atrial fibrillation management by a sample of Italian cardiologist experts in arrhythmia management. Further studies are needed to explore if these divergences are associated with different long-term outcomes.

The gray areas of oral anticoagulation for prevention of thromboembolic events in atrial fibrillation patients.

Thromboembolic events (TEE) associated with atrial fibrillation (AF) are highly recurrent and usually severe, causing permanent disability or, even, death. Previous data consistently showed significantly lower TEE in anticoagulated patients. While warfarin, a vitamin K antagonist, is still used worldwide, direct-acting oral anticoagulants (DOACs) have shown noninferiority to warfarin in the prevention of TEE, and represent, to date, the preferred treatment. DOACs present favorable pharmacokinetic, safety and efficacy profiles, especially among vulnerable patients including the elderly, those with renal dysfunction or previous TEE. Yet, regarding specific settings of AF patients it is unclear whether oral anticoagulation therapy is beneficial, or otherwise it is the maintenance of sinus rhythm, mostly achieved through a catheter ablation-based rhythm control strategy, that prevents the causal complications linked to AF. While it is known that low-risk patients [CHA2DS2-VASc 0 (males), or score of 1 (females)] present low ischemic stroke or mortality rates (<1%/year), it remains unclear whether they need any prophylaxis. Furthermore, the appropriate anticoagulation regimen for those individuals requiring cardioversion, either pharmacologic or electric, as well as peri-procedural anticoagulation in patients undergoing trans-catheter ablation that nowadays encompasses different energies, are still a matter of debate. In addition, AF concomitant with other clinical conditions is discussed and, lastly, the choice of prescribing anticoagulation to asymptomatic patients diagnosed with subclinical AF at either wearable or implanted devices. The aim of this review will be to provide an update on current strategies in the above-mentioned settings, and to suggest possible therapeutic options, finally focusing on AF-related cognitive decline.

The Italian Society of Cardiology and Working Group on Telecardiology and Informatics 2023 updated position paper on telemedicine and artificial intelligence in cardiovascular disease.

In 2015, the Italian Society of Cardiology and its Working Group on Telemedicine and Informatics issued a position paper on Telecardiology, resuming the most eminent evidence supporting the use of information and communication technology in principal areas of cardiovascular care, ranked by level of evidence. More than 5 years later and after the global shock inflicted by the SARS-CoV-2 pandemic, an update on the topic is warranted. Recent evidence and studies on principal areas of cardiovascular disease will be therefore reported and discussed, with particular focus on telemedicine for cardiovascular care in the COVID-19 context. Novel perspectives and opportunities disclosed by artificial intelligence and its applications in cardiovascular disease will also be discussed. Finally, modalities by which machine learning have realized remote patient monitoring and long-term care in recent years, mainly filtering critical clinical data requiring selective hospital admission, will be provided.

Corrigendum: Predictors of late arrhythmic events after generator replacement in Brugada syndrome treated with prophylactic ICD.

[This corrects the article DOI: 10.3389/fcvm.2022.964694.].

[Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part II: From preventive strategies to treatment of patients with cardio-renal damage]. / Documento di consenso Società Italiana di Cardiologia- Società Italiana di Nefrologia: Ruolo dell'asse cardio-renale nella prevenzione e trattamento delle patologie cardiovascolari ­ Parte II: Dalle strategie di prevenzione al trattamento del paziente con coinvolgimento cardio-renale.

Chronic kidney disease and cardiovascular disease are strictly connected each other with a bidirectional interaction. Thus, the prevention of cardio-renal damage, as its appropriate treatment, are essential steps for a correct management of long-term patients' prognosis. Several preventive and therapeutic strategies, pharmacological and not, are now available for cardio-renal damage prevention and treatment, and for the management of its complications. The second part of this consensus document focuses on the management and treatment of cardio-renal damage, directing the attention on the correct use of drugs that may slow renal disease progression, on the application of preventive strategies in case of invasive cardiac procedures with the use of contrast agents, and on the accurate use of cardiological drugs in patients with chronic kidney disease.

Predictors of late arrhythmic events after generator replacement in Brugada syndrome treated with prophylactic ICD.

Introduction: Predictors of late life-threatening arrhythmic events in Brugada syndrome (BrS) patients who received a prophylactic ICD implantation remain to be evaluated. The aim of the present long-term multicenter study was to assess the incidence and clinical-electrocardiographic predictors of late life-threatening arrhythmic events in BrS patients with a prophylactic implantable cardioverter defibrillator (ICD) and undergoing generator replacement (GR). Methods: The study population included 105 patients (75% males; mean age 45 ± 14years) who received a prophylactic ICD and had no arrhythmic event up to first GR. Results: The median period from first ICD implantation to last follow-up was 155 (128-181) months and from first ICD Implantation to the GR was 84 (61-102) months. During a median follow-up of 57 (38-102) months after GR, 10 patients (9%) received successful appropriate ICD intervention (1.6%/year). ICD interventions included shock on ventricular fibrillation (n = 8 patients), shock on ventricular tachycardia (n = 1 patient), and antitachycardia pacing on ventricular tachycardia (n = 1 patient). At survival analysis, history of atrial fibrillation (log-rank test; P = 0.02), conduction disturbances (log-rank test; P < 0.01), S wave in lead I (log-rank test; P = 0.01) and first-degree atrioventricular block (log-rank test; P = 0.04) were significantly associated with the occurrence of late appropriate ICD intervention. At Cox-regression multivariate analysis, S-wave in lead I was the only independent predictor of late appropriate ICD intervention (HR: 9.17; 95%CI: 1.15-73.07; P = 0.03). Conclusions: The present study indicates that BrS patient receiving a prophylactic ICD may experience late appropriate intervention after GR in a clinically relevant proportion of cases. S-wave in lead I at the time of first clinical evaluation was the only independent predictor of persistent risk of life-threatening arrhythmic events. These findings support the need for GR at the end of service regardless of previous appropriate intervention, mostly in BrS patients with conduction abnormalities.