[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis and Cardiovascular Disease in the Adult US Population.

Background: Cardiovascular disease (CVD) risk is higher in patients with nonalcoholic fatty liver disease (NAFLD). Aim: To evaluate whether this can be attributed to the link between NAFLD and known CVD risk factors or to an independent contribution of liver steatosis and fibrosis. Methods: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included participants older than 40 years with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. History of CVD was self-reported and defined as a composite of coronary artery disease and stroke/transient ischemic attacks. Results: Among the 2734 included participants, prevalence of NAFLD was 48.6% (95% CI 45.1-51.4), 316 participants (9.7%, 95% CI 8.1-11.6) had evidence of significant liver fibrosis and 371 (11.5%, 95% CI 9.5-13.9) had a history of CVD. In univariate analysis, patients with CVD had a higher prevalence of steatosis (59.6% vs 47.1%, p=0.013), but not fibrosis (12.9% vs 9.3%, p=0.123). After adjustment for potential confounders in a multivariable logistic regression model, neither steatosis nor significant fibrosis were independently associated with CVD and heart failure. Conclusions: In this population-based study, we did not identify an independent association between steatosis and fibrosis and CVD. Large prospective cohort studies are needed to provide a more definitive evidence on this topic.

[ANMCO position paper on sacubitril/valsartan in the management of patients with heart failure]. / Position paper ANMCO sull'utilizzo della terapia con sacubitril/valsartan nel paziente con scompenso cardiaco.

Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction (HFrEF) since the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin-aldosterone system activation through blockade of angiotensin II type 1 receptors and enhances the activity of vasoactive peptides including natriuretic peptides, through inhibition of neprilysin, the enzyme responsible for their degradation. In the landmark PARADIGM-HF trial, patients with HFrEF treated with sacubitril/valsartan had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, a 20% lower risk of cardiovascular death, a 21% to 20% lower risk of a first heart failure hospitalization, and a 16% to 20% lower risk of death from any cause, compared with subjects allocated to enalapril (all p<0.001).Following the trial, new international guidelines endorsed sacubitril/valsartan as a class I recommendation for the management of patients with HFrEF who remain symptomatic despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed by the National Health Service since March 2017 within criteria set by the Italian Medicines Agency subject to patient inclusion in a dedicated monitoring registry. Although numerous post-hoc analyses of the original trial suggested that the benefits of this innovative medication may extend across a variety of subgroups, many questions do not yet have an evidence-based answer.In this position paper, we discuss the current role of sacubitril/valsartan in the management of chronic HFrEF, treatment eligibility and the modulating role of patients' characteristics. Moreover, we address concerns elicited by the PARADIGM-HF study and shortcomings of this novel drug, to clarify the place of this new therapy in the context of global care of heart failure in Italy. Our aim is to provide clinical cardiologists with a concise and practical guidance on when and how to use sacubitril/valsartan, to assist clinicians in closing the gap between scientific innovation and real-world experience.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry.

BACKGROUND: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. METHODS: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. RESULTS: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). ß-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. CONCLUSIONS: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

Transaortic Chordal Cutting: Mitral Valve Repair for Obstructive Hypertrophic Cardiomyopathy With Mild Septal Hypertrophy.

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal hypertrophy, mitral valve (MV) abnormalities may play an important role in MV displacement into the left ventricular (LV) outflow tract. Therefore, isolated myectomy may not relieve outflow obstruction and symptoms, and MV replacement is often the surgical alternative. OBJECTIVES: This study sought to assess the clinical and hemodynamic results of cutting thickened secondary MV chordae combined with a shallow septal muscular resection in severely symptomatic patients with obstructive HCM and mild septal hypertrophy. METHODS: Clinical features were compared before surgery and at most recent clinical evaluation in 39 consecutive patients with obstructive HCM. RESULTS: Over a 23 ± 2 months follow-up, New York Heart Association functional class decreased from 2.9 ± 0.5 pre-operatively to 1.1 ± 1.1 post-operatively (p < 0.001), with no patient in class III at most recent evaluation. The resting outflow gradient decreased from 82 ± 43 mm Hg to 9 ± 5 mm Hg (p < 0.001) and septal thickness decreased from 17 ± 1 mm to 14 ± 2 mm (p < 0.001). No patient had MV prolapse or flail and 1 had residual moderate-to-severe MV regurgitation at most recent evaluation. MV geometry before and after surgery was compared with that of 25 consecutive patients with similar clinical profile and septal thickness that underwent isolated myectomy. After adjustment for differences in pre-operative values between the groups, the post-operative anterior MV leaflet-annulus ratio was 17% greater and tenting area 24% smaller in patients with chordal cutting, indicating that MV apparatus had moved to a more normal posterior position within the LV cavity, preventing MV systolic displacement into the outflow tract and outflow obstruction. CONCLUSIONS: This procedure relieves heart failure symptoms, abolishes LV outflow gradient, and avoids MV replacement in patients with obstructive HCM and mild septal thickness.

Neutrophil gelatinase-associated lipocalin predicts worsening of renal function in acute heart failure: methodological and clinical issues.

BACKGROUND: Worsening of renal function (WRF) in acute heart failure (AHF) strongly predicts adverse clinical outcome. Plasma neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as an earlier biomarker of tubular damage, but important methodological issues remain unsolved, particularly in AHF. METHODS AND RESULTS: In 30 consecutive patients admitted for AHF, 108 serum NGAL (Alere system) measurements were performed at entry and in the first days of recovery, and reproducibility within the same blood samples was very high (r = 0.98). NGAL at entry was related to kidney function [r = 0.51 vs. creatinine (Cr) and r = -0.49 vs. estimated glomerular filtration rate (eGFR), both P < 0.001], and weakly with hemoglobin (r = -0.36, P < 0.05) and C-reactive protein (CRP) (r = 0.26, P < 0.05). During hospitalization, WRF occurred in 26.7% of the patients. Baseline NGAL was only slightly higher in patients who developed WRF as compared to those who did not (151 ±â€Š90 vs. 119 ±â€Š75 ng/ml, NS), but it increased significantly in the following days, always preceding WRF occurrence (max. previous 24 h, average 95%, range 25-200%). The area under the Receiver Operating Characteristic (ROC) curve (AUC-ROC) was 0.69 for pathological NGAL at entry and 0.91 for delta NGAL changes during the first days. CONCLUSIONS: In patients with AHF, serum NGAL measurement is highly reproducible and at entry it is related to baseline Cr and eGFR, but does not predict WRF during subsequent hospitalization. On the contrary, serial measurements of NGAL in the first days of hospitalization can accurately predict WRF.

Long-term outcome and risk stratification in dilated cardiolaminopathies.

OBJECTIVES: The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. BACKGROUND: Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. METHODS: Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. RESULTS: Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. CONCLUSIONS: Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.