Italian Association of Hospital Cardiologists practical guidance for sodium-glucose cotransporter 2 inhibitors use in patients with heart failure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-is) have recently been included among the first-line drugs for the treatment of heart failure with reduced ejection fraction. International guidelines recommend SGLT2-i use in association with neuro-hormonal modulators (renin-angiotensin blockers, beta blockers, and aldosterone antagonists). Although SGLT2-is are well tolerated, it is important to know potential side effects and conditions that may lead to an increased risk of adverse events in order to maximize clinical benefits. The aim of this Italian Association of Hospital Cardiologists document is to briefly report clinical evidence that supports SGLT2-i use in patients with heart failure and provide practical indications for clinical implementation.

ANMCO position paper on vericiguat use in heart failure: from evidence to place in therapy.

In the growing therapeutic armamentarium for heart failure (HF) management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for HF. Indeed, vericiguat does not inhibit neuro-hormonal systems overactivated in HF or sodium-glucose co-transporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with HF. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with HF and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening HF. This ANMCO position paper summarises key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.

Tako-Tsubo syndrome in patients with COVID-19: a single centre retrospective case series.

Growing evidence shows that COVID-19 is associated with an increase in Tako-Tsubo syndrome (TTS) incidence. We collected data from patients hospitalized in our multidisciplinary COVID-19 department who had a diagnosis of TTS during the second and third wave of the pandemic in Italy. We reported four cases of TTS associated with COVID-19. No patient had any classical trigger for TTS except for COVID-19. Mean age was 72 years (67-81) and all patients had a SARS-CoV-2-related interstitial pneumonia confirmed by computed tomography. Typical apical ballooning and transitory reduction in left ventricle (LV) systolic function with a complete recovery before discharge were observed in all patients. The mean LV ejection fraction (LVEF) at TTS onset was 42% (40-48%). ECG showed ST-segment elevation in two cases, while an evolution with negative T waves and QTc prolongation was observed in all patients. Three patients underwent coronary angiography. Two patients had Alzheimer's disease. The time interval from hospital admission to TTS onset was 4 (2-6) days, and the time interval from COVID-19 symptom onset to TTS diagnosis was 10 (8-12) days.  COVID-19 may be a trigger for TTS, though TTS pathophysiology in COVID-19 patients remains unclear, likely due to its multifactorial nature.

Effect of fixed-rate vs. rate-RESPONSIve pacing on exercise capacity in patients with permanent, refractory atrial fibrillation and left ventricular dysfunction treated with atrioventricular junction aBLation and bivEntricular pacing (RESPONSIBLE): a prospective, multicentre, randomized, single-blind study.

AIMS: Atrioventricular junction (AVJ) ablation followed by biventricular pacing is an established strategy for improving symptoms and morbidity in patients with permanent atrial fibrillation (AF), reduced left ventricular ejection fraction (LVEF), and uncontrolled ventricular rate. There is no clear evidence that such patients benefit from rate-responsive (RR) pacing. METHODS AND RESULTS: This prospective, randomized, single-blind, multicentre study was designed as an intra-patient comparison and enrolled 60 patients (age 69.5 ± 11.8 years, males 63.3%, NYHA 3.0 ± 0.6) with refractory AF and reduced LVEF (mean 32.4 ± 8.3%) treated with AVJ ablation and biventricular pacing. Two 6-minute walking tests (6MWT) were performed 1 week apart: one during VVI 70/min biventricular pacing and the other during VVIR 70-130/min biventricular pacing; patients were randomly and blindly assigned to Group A (n = 29, first 6MWT in VVIR mode) or B (n = 31, first 6MWT in VVI mode). Rate-responsive activation determined an increase of 18.8 ± 24.4 m in the distance walked during the 6MWT (P < 0.001). The increase was similar in both groups (P = 0.571). A >5% increase in the distance walked was observed in 76.7% of patients. The increase in the distance walked was linearly correlated with the increase in heart rate recorded during the 6MWT in the VVIR mode (r = 0.54; P < 0.001). CONCLUSION: In permanent AF patients with uncontrolled rate and reduced LVEF who had undergone AVJ ablation and biventricular pacing, RR pacing yields a significant gain in exercise capacity, which seems to be related to the RR-induced frequency during effort.

Clinically guided pacemaker choice and setting: pacemaker expert programming study.

AIM: The aim of this multicentre, observational, transversal study was to evaluate pacemaker (PM) choice and setting in a large number of patients, in order to understand their relationship with the patients' clinical characteristics. METHODS AND RESULTS: The study enrolled a total of 1858 patients (71 ± 14 years, 54% male), consecutively evaluated during scheduled PM follow-up visits in 7 Italian cardiac arrhythmia centres. To evaluate the appropriateness of PM choice in relation to the patients' clinical characteristics, we analysed their rhythm disorders at the time of device implantation and the characteristics of the devices implanted. To evaluate the appropriateness of device setting, current rhythm disorders and device setting at the time of enrolment were analysed. In the overall study population, 64.3% of the patients received a PM with all of the features required for their rhythm disorder [80.8% in persistent atrioventricular (AV) block, 76.5% in atrial fibrillation needing pacing, 71.0% in sinus node disease, 58.7% in non-persistent atrioventricular block (AVB), 52.7% in neuro-mediated syncope]. The most frequent cause of inappropriate PM choice was the lack of an algorithm to promote intrinsic AV conduction in non-persistent AVB patients (38.1%). In 76.2% of the patients with an appropriate PM (n = 1301), the PM was optimally set for their rhythm disorder. CONCLUSIONS: In the present 'real-world' registry, a large number of patients (35.7%) did not receive an optimal PM for their rhythm disorders. Moreover, one-fourth of appropriate PMs were not programmed according to the patients' clinical characteristics.

Prevalence and predictor factors of severe venous obstruction after cardiovascular electronic device implantation.

AIMS: Despite not being uncommon, limited evidence exists about predisposing factors for venous obstruction in patients with implantable electronic devices. We aimed to assess the prevalence of severe venous obstruction in patients with intravenous devices and identify predictor factors. METHODS AND RESULTS: A total of 184 patients underwent venography to detect venous obstruction associated with the inserted lead. Vessel obstruction was graded as venous occlusion (complete flow interruption), severe obstruction (narrowing >90%), or mild-moderate obstruction (narrowing 50-90%). Severe venous obstruction/occlusion prevalence was 11.4% (n = 21) and was always asymptomatic. Collateral circulation was found in 80.9% of patients with severe obstruction/occlusion. Twelve patients (6.5%) had 3 leads. The rates of patients with secondary prevention of sudden cardiac death as indication for implantable devices and of those of patients with 3 leads were significantly greater in the group with severe obstruction/occlusion than in the non-severe obstruction/occlusion group (respectively, P = 0.004 and P = 0.03). Logistic analysis adjusted for venous thromboembolic risk factors confirmed that secondary prevention of sudden cardiac death as indication for implantable devices [odds ratio (OR), 7.1; 95% confidence interval (CI): 1.4-35.3; P = 0.017] and the presence of 3 leads (OR, 8.5; 95% CI: 1.75-41.35; P = 0.008) were predictors of severe obstruction/occlusion. CONCLUSION: In patients with implantable devices, severe venous obstruction prevalence is not negligible and the lack of symptoms does not exclude it. The presence of three leads and sudden cardiac death as indication for implantable devices seem to be associated with the presence of severe venous obstruction/occlusion.

[Adherence to pharmacological treatments: searching for new solutions]. / Aderenza ai trattamenti farmacologici: alla ricerca di nuove soluzioni.

Adherence to prescribed treatments is an essential prerequisite for a therapy to be effective. In cardiology, poor therapeutic adherence is a problem that affects 50% of patients in primary prevention and 44% in secondary prevention, with a consequent significant impact on prognosis and global health costs. In this review, we analyze the possible causes of poor adherence and discuss possible interventions to be implemented to address this problem. In detail, we briefly report the evidence supporting deprescribing, the use of the polypill, the innovative treatments with gene silencing, and digital technologies as potential approaches to improve adherence in the cardiovascular field.

Appropriate use of wearable defibrillators with multiparametric evaluation to avoid unnecessary defibrillator implantation.

INTRODUCTION: Wearable cardioverter-defibrillators (WCD) have emerged as a valuable tool in the management of patients at risk for life-threatening arrhythmias. These devices offer a non-invasive and temporary solution, providing continuous monitoring and the potential for prompt defibrillation when needed. In this study, we explore the use of WCD and evaluate arrhythmic events through comprehensive monitoring. METHODS: From November 2022 to May 2024, we conducted an outpatient follow-up of 41 patients receiving WCD. Regular check-ups, remote monitoring and comprehensive echocardiography were performed to optimise a tailored therapy. RESULTS: The average age of the patients was 59.2.4±16.5 years, with 78% being male. Among the cohort, 54% had hypertension, 41% were smokers and 66% had dyslipidaemia, while 27% were diabetic. WCD was assigned according to the Italian Association of Hospital Cardiologists position paper focussing on the appropriate use of WCD and European Society of Cardiology guidelines on ventricular arrhythmias and the prevention of sudden cardiac death: 24 (58%) patients had a de novo diagnosis of heart failure with reduced ejection fraction, 11 (27%) patients had a recent acute coronary syndrome and ejection fraction <35%, 3 (7%) patients had a cardiac electronic device extraction and 3 (7%) patients had myocarditis with features of electrical instability. The average follow-up was 62±38 days according to specific aetiology, with a daily wearing time of 22.7±1.3 hours. No device interventions were recorded. At the end of the follow-up period, 15 patients still required an implantable cardioverter-defibrillator (ICD). Among these, 12 patients (29%) underwent ICD implantation. Two patients (5%) declined the procedure. CONCLUSIONS: The use of WCD for patients at high risk of arrhythmias allowed to optimise therapy and limit the indications for ICD. Inappropriate implantation of ICD was avoided in 69% of patients who received WCD. The device showed a good safety profile, low incidence of device interventions and adequate patients' adherence to WCD use.

Prevention and Risk Assessment of Cardiac Device Infections in Clinical Practice.

The implantation of cardiac electronic devices (CIEDs), including pacemakers and defibrillators, has become increasingly prevalent in recent years and has been accompanied by a significant rise in cardiac device infections (CDIs), which pose a substantial clinical and economic burden. CDIs are associated with hospitalizations and prolonged antibiotic therapy and often necessitate device removal, leading to increased morbidity, mortality, and healthcare costs worldwide. Approximately 1-2% of CIED implants are associated with infections, making this a critical issue to address. In this contemporary review, we discuss the burden of CDIs with their risk factors, healthcare costs, prevention strategies, and clinical management.

[Low and very low cholesterol levels: what we need to know]. / Livelli di colesterolo bassi e molto bassi: cosa è necessario sapere.

Due to the growing evidence of clinical benefits conferred by the reduction of low-density lipoprotein cholesterol (LDL-C) levels, the availability of multiple effective lipid-lowering agents, and guideline recommendations, clinicians not infrequently have to manage patients with low or very low LDL-C levels. In clinical practice it is essential to consider that, when LDL-C plasma concentrations are low, the Friedewald formula commonly used for LDL-C level calculation is less accurate, hence risk assessment should be integrated by using different methods for LDL-C level quantification and other parameters, such as non-high-density lipoprotein cholesterol and, where possible, apolipoprotein B, should be measured. As regards the clinical impact of low LDL-C levels, genetically determined hypocholesterolemia forms provide reassuring data on the effects of this condition in the long term, except for the forms with extremely low or undetectable LDL-C levels. Evidence from clinical studies that used highly effective lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, goes in the same direction. In these studies, the incidence of non-cardiovascular adverse events in patients who reached very low LDL-C levels was similar to that in the placebo arm. Overall, the fear of adverse effects should not deter intensive lipid-lowering treatment when indicated to reduce the risk of cardiovascular events.

Emergency reversal of vitamin-K antagonists related over-anticoagulation: case report and brief overview on the role of prothrombin complex concentrate.

Oral anticoagulation is a widely used treatment and atrial fibrillation (AF) is the most frequent indication. We review the therapeutic options on an important clinical challenge: rapid reversal anticoagulation in the setting of an urgent invasive procedure. We report a case of a 71-year-old man treated with warfarin who was over-anticoagulated when presented to the emergency department for syncope due to severe bradiarrhythmia and needed temporary pacing. Intravenous infusion of vitamin-k was not adequate for rapid reversal over anticoagulation whereas the administration of a Prothrombin Complex Concentrate (PCC) was able to quickly reverse anticoagulant activity and allowed the performance of an urgent invasive procedure without hemorrhagic complication. The aim of this paper is to draw attention to possible therapeutic strategies to reduce the risk of bleeding related to over-anticoagulation with vitamin-K antagonists (VKAs) in case of urgent invasive procedure, emphasizing the role of PCC in keeping with national and international guidelines.

[ANMCO practical guide for sodium-glucose cotransporter 2 inhibitor use in patients with heart failure]. / Guida pratica ANMCO all'impiego degli inibitori del cotrasportatore sodio-glucosio di tipo 2 nei pazienti con scompenso cardiaco.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), initially developed as glucose-lowering agents for the treatment of type 2 diabetes, based on significant clinical benefits shown in patients with heart failure, have recently been included among the first-line drugs for the treatment of heart failure with reduced ejection fraction. International guidelines recommend SGLT2-i use in association with neuro-hormonal modulators (renin-angiotensin blockers, beta-blockers, and aldosterone antagonists). Although SGLT2-i are well tolerated, for an appropriate use and to maximize clinical benefits, it is important to know potential side effects and conditions that may lead to an increased risk of adverse events. The aim of this ANMCO document is to briefly report clinical evidence that support SGLT2-i use in patients with heart failure and provide practical indications for clinical implementation.

The polypill strategy in cardiovascular disease prevention: It's time for its implementation.

A polypill strategy has been demonstrated to improve treatment adherence in several cardiovascular disease (CVD) settings. However, data on the prognostic impact in the secondary prevention setting have been scarce. The Secondary Prevention of Cardiovascular Disease in the Elderly trial, the results of which have been recently published, has demonstrated a benefit in terms of major adverse CVD event reduction. This finding, in addition to previous evidence, should lead to a broader polypill implementation in CVD prevention.

[ANMCO Position paper: Colchicine as a therapeutic agent in coronary syndromes]. / Position paper ANMCO: La colchicina come agente terapeutico nelle sindromi coronariche.

With the growing knowledge about the role of inflammatory processes in the pathogenesis of atherosclerotic lesions, inflammation has been identified as a cardiovascular risk factor and therapeutic target to reduce the residual risk in patients with atherosclerotic disease. Several therapeutic agents with anti-inflammatory action have been tested to evaluate their efficacy and safety in the context of atherosclerotic cardiovascular diseases. Among these, colchicine, a drug with multiple therapeutic effects including anti-inflammatory action, in randomized clinical trials conducted in the setting of atherosclerotic cardiovascular disease secondary prevention, significantly reduced the risk of adverse cardiovascular events.This position paper of the Italian Association of Hospital Cardiologists (ANMCO) summarizes the main biological mechanisms through which colchicine contributes to the inhibition of inflammatory processes that increase the atherosclerotic cardiovascular risk. Furthermore, the document reports the available evidence on clinical impact of colchicine treatment in the reduction of residual cardiovascular risk in chronic and acute coronary syndromes. Finally, practical information is provided regarding the use of this drug in this specific clinical setting, emphasizing precautions and possible side effects.

[Gut microbiota as an atherosclerotic risk factor: from biological mechanisms to potential therapeutic interventions]. / Il microbiota intestinale come fattore di rischio aterosclerotico: dai meccanismi biologici ai possibili interventi terapeutici.

Gut microbiota impacts host health by mediating beneficial physiological processes. However, growing evidence supports the potential role of microbiota in disease development and progression. In this review, we report current knowledge on pathophysiologic processes mediated by gut microbiota that may be implicated in atherosclerosis development and progression. We also summarize findings provided by clinical studies that indicate an association between gut microbiota composition and/or function and atherosclerotic cardiovascular diseases. Finally, we discuss potential strategies to impact gut microbiota composition and/or function in order to reduce the atherosclerotic cardiovascular risk.

[ANMCO statement: Uric acid and cardiovascular disease: evidence and therapeutic approach]. / Statement ANMCO: Acido urico e malattie cardiovascolari: evidenze e approccio terapeutico.

Pathophysiologic processes promoted by uric acid, including inflammation and oxidative stress, play a key role in the pathogenesis of several cardiovascular diseases. Furthermore, a number of epidemiological studies have shown an association between uric acid plasma levels and multiple cardiovascular risk factors. This ANMCO statement provides an update on available evidence regarding the association between elevated plasma uric acid levels and cardiovascular disease risk and the safety and efficacy of uric acid lowering agents (allopurinol and febuxostat) used in patients with urate crystal deposits. In addition, it summarizes practical indications for the use of these drugs in at-risk patients or in patients with cardiovascular disease.

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]. / ANMCO Expert opinion: Posizionamento terapeutico dell'acido bempedoico nel trattamento dell'ipercolesterolemia.

Growing evidence supporting the central role of hypercholesterolemia in atherosclerotic disease pathogenesis and progression has led to the development of new therapeutic approaches. Bempedoic acid has recently been approved for marketing following several studies that demonstrated its efficacy and safety. This drug represents a new therapeutic option that, like statins, acts on the enzymatic cascade that is involved in cholesterol synthesis. However, its hepatic selectivity of action reduces the risk of muscle adverse effects. This ANMCO document highlights clinical settings in which bempedoic acid represents a particularly useful therapeutic option. Furthermore, the document discusses the possibilities of use based on both international recommendations and current national regulations. Finally, we report practical guidance on hypercholesterolemia management in light of the available therapeutic armamentarium.

[ANMCO Position paper: Inclisiran: an innovative therapeutic approach for the clinical management of hypercholesterolemia]. / Position paper ANMCO: Inclisiran: un approccio terapeutico innovativo per la gestione dell'ipercolesterolemia.

Research focused on lipid-lowering treatments has led to the development of new therapeutic options aimed at cardiovascular risk reduction. Gene silencing represents one of the most innovative approaches to reduce low-density lipoprotein cholesterol (LDL-C). Inclisiran is a small interfering RNA that inhibits proprotein convertase subtilisin/kexin type 9 synthesis and promotes LDL-C clearance by enhancing LDL-C receptor expression on hepatocyte cell surface. Several clinical studies have demonstrated inclisiran efficacy in terms of LDL-C reduction (~50%) with a dosage regimen of 300 mg administered twice a year after the first two doses administered at time 0 and after 90 days. Inclisiran use has recently been approved by the European and American drug regulatory agencies as a therapeutic option in addition to the maximum tolerated statin therapy in adults with primary hypercholesterolemia or mixed dyslipidemia who need further LDL-C reduction.

[The early use of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and high cardiovascular risk]. / L'impiego degli agonisti recettoriali del glucagon-like peptide 1 nel trattamento precoce e nel continuum cardiovascolare dei pazienti con diabete di tipo 2 ad alto rischio cardiovascolare.

Patients with type 2 diabetes mellitus are at an increased risk of cardiovascular disease and microvascular and macrovascular complications. Although multiple classes of antidiabetic drugs are currently available, cardiovascular complications of diabetes still cause considerable morbidity and premature cardiovascular mortality in diabetic patients. The development of new drugs represented a conceptual breakthrough in the treatment of patients with type 2 diabetes mellitus. In addition to improving glycemic homeostasis, these new treatments have consistently demonstrated relevant cardiovascular and renal benefits due to their multiple pleiotropic effects. The aim of this review is to analyze the direct and indirect mechanisms by which glucagon-like peptide 1 receptor agonists favorably impact cardiovascular outcome and report current indications for their implementation in clinical practice based on national and international guidelines.

[Degenerative aortic valve stenosis: looking for a pharmacological prevention]. / Stenosi valvolare aortica degenerativa: alla ricerca di una prevenzione farmacologica.

Degenerative calcific aortic valve stenosis (CAVS) is a chronic disease whose prevalence has increased over the last decade because of the aging of the general population. CAVS pathogenesis is characterized by complex molecular and cellular mechanisms that promote valve fibro-calcific remodeling. During the first phase, referred to as initiation, the valve undergoes collagen deposition and lipid and immune cell infiltration due to mechanical stress. Subsequently, during the progression phase, the aortic valve undergoes chronic remodeling through osteogenic and myofibroblastic differentiation of interstitial cells and matrix calcification. Knowledge of the mechanisms underlying CAVS development supports the resort to potential therapeutic strategies that interfere with fibro-calcific progression. Currently, no medical therapy has demonstrated the ability to significantly prevent CAVS development or slow its progression. The only treatment available in symptomatic severe stenosis is surgical or percutaneous aortic valve replacement. The aim of this review is to highlight the pathophysiological mechanisms involved in CAVS pathogenesis and progression and to discuss potential pharmacological treatments able to inhibit the main pathophysiological mechanisms of CAVS, including lipid-lowering treatment with lipoprotein(a) as emergent therapeutic target.