[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.

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.

[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.

[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.

[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.

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.

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.

[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.

[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 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.

Potential pathophysiologic mechanisms underlying the inherent risk of cancer in patients with atherosclerotic cardiovascular disease.

Emerging evidence demonstrates an intimate interplay between cardiovascular disease and cancer pathophysiology. The aim of this review is to shed light on the common biological pathways underlying cardiovascular disease and cancer. These common pathways form the basis of "reverse cardio-oncology". We focus on the role of inflammation, stress response, cell proliferation, angiogenesis and tissue remodeling, neurohormonal system activation, and genomic instability as pathogenic pathways shared by cardiovascular disease and cancer. We also discuss shared mediators that may have a potential role as biomarkers for risk prediction in both diseases. Furthermore, we highlight current knowledge on biological pathways and mediators that are upregulated in diabetes and myocardial infarction and may be involved in tumorigenesis. On the basis of the shared pathophysiologic mechanisms, we also suggest an integrated approach to reduce the global burden of both cardiovascular disease and cancer.

[Importance of the individualized care process in a patient with recurrent acute coronary syndrome, multiple comorbidities and depressive syndrome]. / Importanza del processo assistenziale individualizzato nel paziente con sindrome coronarica acuta ricorrente, comorbilità multiple e sindrome depressiva. Descrizione di un caso clinico.

Statins have pleiotropic effects, including anti-inflammatory action, which is class-specific and contributes to a reduction in cardiovascular events. Statins also have a potential antidepressant effect. We report the case of a patient with depressive disorder and very high cardiovascular risk, in whom idiopathic myelofibrosis was also diagnosed. Due to the potential interaction of the antitumor drug (ruxolitinib) with atorvastatin and sertraline at the level of cytochrome P450, the latter two drugs were discontinued. The patient was referred for cognitive-behavioral treatment and the combination of rosuvastatin/ezetimibe was prescribed. This drug combination led to the achievement of optimal cholesterol targets in the absence of metabolic interference with ruxolitinib and adverse events. This strategy allowed the continuation of antitumor therapy and led to a hematological improvement. The antidepressant effect of statins, in addition to cognitive-behavioral treatment, may have contributed to the improvement in the patient's psychological status.

Impact of Working from Home on Cardiovascular Health: An Emerging Issue with the COVID-19 Pandemic.

Mandatory working from home is one of the consequences of the COVID-19 pandemic for a large number of workers. Transition to working from home may significantly impact lifestyle, psychosocial status, and the overall health of workers. This review summarizes available data about the effects of lockdown measures, particularly working from home, on cardiovascular risk factors including sedentary lifestyle, unhealthy diet pattern, psychological distress, smoking, alcohol misuse, and cardiometabolic parameters. Finally, we suggest countermeasures that can attenuate the negative health impact of working from home. Indeed, timely and tailored interventions implemented by companies in cooperation with the health care system could allow workers to benefit more from some of the advantages associated with working from home.

Do Pathophysiologic Mechanisms Linking Unhealthy Lifestyle to Cardiovascular Disease and Cancer Imply Shared Preventive Measures?　- A Critical Narrative Review.

Growing evidence has shown a bidirectional link between the cardiologic and oncologic fields. Several investigations support the role of unhealthy behaviors as pathogenic factors of both cardiovascular disease and cancer. We report epidemiological and research findings on the pathophysiological mechanisms linking unhealthy lifestyle to cardiovascular disease and cancer. For each unhealthy behavior, we also discuss the role of preventive measures able to affect both cardiovascular disease and cancer occurrence and progression.

The Malone antegrade continence enema adapting a transanal irrigation system in patients with neurogenic bowel dysfunction.

INTRODUCTION: Patients with severe neurogenic bowel dysfunction (NBD) may undergo the Malone antegrade continence enema (MACE) surgery to perform antegrade bowel irrigation (ABI). The standard approach may be prevented by a previous appendectomy or complicated by appendicular stenoses and/or stomal leakages. We present the experience by our tertiary referral center for NBD, adopting a modified surgical technique, based on a neoappendix with the terminal ileum to preserve the natural anti-reflux mechanism of the ileocecal valve and avoid stool leakage, and a largely available transanal irrigation (TAI) system to catheterize the neoappendix and perform ABI. CASE PRESENTATION: Three individuals with NBD successfully underwent our modified MACE program. Case 1 had cauda equina syndrome. He underwent surgery at 40. Case 2 was a man who suffered from spinal cord dysfunction due to acute disseminated encephalomyelitis, functionally T12 AIS B, at 57. Case 3 was a man with traumatic L1 AIS B paraplegia. At 60 he underwent surgery after 29 years since the injury. He needed a surgical revision due to a postoperative subcutaneous infection. After 121, 84 and 14 months from surgery, the three individuals performed ABI every 2 days, presented functional stomas, had no fecal incontinence, and reported an NBD score of 6, compared to 40, 33 and 35 pre-operatively. DISCUSSION: To our knowledge, this is the first report of MACE combining a tapered terminal ileum conduit and an adapted TAI system. Our approach proved to be a safe and effective strategy for severe NBD avoiding a colostomy.

T-wave alternans in apparently healthy subjects and in different subsets of patients with ischaemic heart disease.

AIMS: Microvolt T-wave alternans (TWA) predicts arrhythmic risk in patients with ischaemic heart disease (IHD). While TWA has widely been assessed by the spectral method, it has been poorly characterized in healthy people as well as in IHD patients by the modified moving average (MMA) method. METHODS AND RESULTS: We enrolled 729 consecutive subjects, referred for exercise stress test (EST). T-wave alternans was assessed by the MMA method, considering all 12 electrocardiogram (ECG) leads (TWA_tot) or the 6 ECG pre-cordial leads only (TWA_prec). Patients were divided into five groups: (i) no history of IHD and normal EST (Group 1); (ii) no history of IHD but positive EST (Group 2); (iii) ischaemic heart disease without any acute myocardial infarction [AMI (Group 3)]; (iv) old AMI (Group 4); (v) recent AMI (Group 5). T-wave alternans values >95th percentile of those measured in Group 1 were considered 'abnormal'. The 95th percentile of TWA values in Group 1 was 75 µV for TWA_tot and 65 µV for TWA_prec. T-wave alternans values and prevalence of abnormal TWA increased from Groups 1-2 to Group 5 (P< 0.00001 for both). Group 4 and Group 5, compared with Group 1, showed a significant higher prevalence of abnormal values of TWA_tot [odds ratio (OR) 1.70 (P= 0.002), and 2.07 (P= 0.01), respectively] and TWA_prec [OR 1.51 (P= 0.02) and 2.37 (P= 0.003), respectively] at multivariable analysis. In IHD patients EST-induced ischaemia did not influence TWA; in AMI patients, impaired left ventricular function was associated with higher TWA values. CONCLUSIONS: In healthy people, TWA_tot and TWA_prec were ≤75 and ≤65 µV, respectively, in 95% of subjects. In IHD patients TWA values were higher compared with healthy individuals; a history of AMI was independently associated with abnormal TWA values.

Electrical and autonomic cardiac function in patients with Dravet syndrome.

Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24-h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age- and sex-matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no-AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no-AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow-up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.

Long-term prognosis of patients with cardiac syndrome X.

BACKGROUND: Previous follow-up studies of patients with cardiac syndrome X (CSX) reported good prognosis. However, some recent reports challenged this finding by showing appreciable mortality rates in patients with angina and normal coronary arteries admitted for acute coronary syndromes. METHODS: We performed clinical follow-up of 155 patients (mean age 58.9+/-10 years, 40 men) with typical CSX. The occurrence of major cardiac events (cardiac death, acute myocardial infarction), readmission for chest pain, revascularization procedures, angina status, and non cardiac events during follow-up were collected for each patient. RESULTS: At a mean follow-up time of 137+/-78 months (range 24-372) from the onset of symptoms, 4 patients died, 3 for cancers and 1 for acute pancreatitis. No patient died from cardiovascular causes or had any major cardiovascular event. Hospital readmission for recurrent chest pain was reported by 89 patients (58%), and 33 (22%) underwent at least one more coronary angiography. During follow-up, chest pain had remained unchanged in 33% of patients and had worsened in 14% of patients. CONCLUSION: Our data show that patients with CSX have excellent long-term clinical prognosis. A significant number of patients, however, shows persistence or worsening of symptoms, as well as further recurrence to medical evaluation.

Effect of spinal cord stimulation on cardiac adrenergic nerve function in patients with cardiac syndrome X.

BACKGROUND: In patients with cardiac syndrome X (CSX) who present with refractory angina episodes, spinal cord stimulation (SCS) has beneficial effects. The mechanisms of SCS, however, remain speculative. We assessed the effects of SCS on cardiac sympathetic function in these patients. METHODS AND RESULTS: We studied 11 CSX patients treated by SCS for refractory angina (mean age, 60 +/- 9 years; 5 men and 6 women), both during SCS therapy (SCS-ON) and after withdrawal of SCS therapy (SCS-OFF), using a randomized crossover design. Planar and single photon emission computed tomography iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and technetium 99m sestamibi (MIBI) bicycle exercise stress testing were performed at the end of each period. Compared with 10 healthy control subjects, CSX patients showed a lower heart-mediastinum ratio for MIBG uptake (2.19 +/- 0.3 vs 1.69 +/- 0.3, P = .001) and a higher cardiac MIBG uptake score (4.0 +/- 2.5 vs 19.7 +/- 27, P = .08). There were no differences in CSX patients during the SCS-ON and SCS-OFF phases of the study in heart-mediastinum ratio (1.74 +/- 0.3 vs 1.69 +/- 0.3, P = .13), cardiac washout rate of MIBG (42.9% +/- 14% vs 43.3% +/- 14%, P = .08), or MIBG defect score (18.7 +/- 25 vs 19.7 +/- 27, P = .22). Reversible perfusion defects during the SCS-OFF phase were detected in 8 patients; an improvement in perfusion defects was observed in 2 patients (25%) during the SCS-ON phase. CONCLUSIONS: Our data confirm the presence of abnormal cardiac adrenergic nerve function in CSX patients. SCS was unable to result in significant improvement of cardiac MIBG uptake abnormalities, suggesting that its therapeutic effects are unlikely to be mediated by modulation of cardiac adrenergic nerve activity.

Long-term follow-up of patients with cardiac syndrome X treated by spinal cord stimulation.

OBJECTIVE: To assess the long-term effect of spinal cord stimulation (SCS) in patients with refractory cardiac syndrome X (CSX). METHODS: A prospective, controlled, long-term follow-up was performed of 19 patients with CSX with refractory angina who underwent SCS (SCS group, 5 men, mean (SD) age 60.9 (8.5) years); 9 comparable patients with CSX who refused SCS treatment (3 men, mean (SD) age 60.9 (8.8) years) constituted the control group. Clinical and functional status were assessed at the time of screening for SCS indication (basal evaluation) and at a median (range) follow-up of 36 (15-82) months. RESULTS: The two groups at baseline did not show any difference in clinical characteristics and angina status. All indicators of angina status (angina episode frequency, duration and short-acting nitrate use) improved significantly at follow-up in the SCS group (p<0.001) but not in controls. Functional status, as assessed by the Seattle Angina Questionnaire and a visual analogue scale for quality of life, improved at follow-up in the SCS group (p<0.001 for all scales) but not in controls. Exercise tolerance, exercise-induced angina and ST segment changes also significantly improved in the SCS group but not in controls. CONCLUSIONS: Data show that SCS can be a valid form of treatment for long-term control of angina episodes in patients with refractory CSX.