Multiple hormone deficiency syndrome: a novel topic in chronic heart failure.

[First paragraph] Heart failure (HF) is described as a clinical syndrome characterized by typical symptoms (e.g., ankle swelling, fatigue or dyspnea) or signs (e.g., peripheral edema, pulmonary crackles or elevated jugular venous pressure), in which structural and/or functional cardiac abnormalities induce an impairment of cardiac output or an increase of intracardiac pressures at rest and/or during stress [1,2]. Importantly, due to different underlying etiologies, demographics, co-morbidities, and response to therapies, the main terminology used to describe HF is based on measurement of left ventricle ejection fraction (EF). Classically, patients with normal EF (typically considered as ≥50%) are said to have HF with preserved EF (HFpEF), with those with reduced EF (typically considered as <40%) termed as HF with reduced EF (HFrEF). In the latest European Society of Cardiology guidelines, cases where EF lies between 40 and 49%, previously considered as a ‘gray area’, are now defined as HF with mid-range EF (HFmEF) [1]

Heart failure and trimethylamine N-oxide: time to transform a ‘gut feeling’ in a fact?

In the last few years, in the context of a growing interest in investigating novel pathways involved in heart failure (HF) pathophysiology, the association between the gastrointestinal (GI) system and HF represents an important model of attention, the so called ‘gut hypothesis’.Despite being classically identified as a ‘simple’ intestinal dysfunction, the main hypothesis is currently focused on the role of inflammation and oxidative stress as a consequence of the intestinal wall ischaemia and/or congestion induced by HF, determining a gut barrier dysfunction and resulting in an increased gut bacterial translocation.With this in mind, two main mechanisms have been proposed to link gut dysfunction and HF; (i) metabolism dependent, via gut-derived metabolites entering the systemic circulation and exerting pro-atherogenic effects and pro-inflammatory effects and (ii) metabolism independent, via bacterial components (e.g. lipopolysaccharides and endotoxins) translocating in the systemic circulation and contributing to the systemic inflammatory state with its well-known negative effects on HF. </p

The Tosca Registry: An Ongoing, Observational, Multicenter Registry for Chronic Heart Failure.

The ageing of the population in western countries, the continuous increase of the prevalence of chronic diseases, the frequent coexistence of several morbid conditions (comorbidity) requires health professionals and Institutions to face difficult challenges, including increasing costs, need for more effective and sustainable therapies, and organizational issues. The European Innovation Partnership on Active and Healthy Ageing aims at enabling European citizens to lead healthy, active and independent lives while ageing. We herein discuss some key concepts bearing a special significance in the light of the Partnership aims, and present research and educational projects active in our local environment. Among these, the multicentre project TOSCA (Trattamento Ormonale nello Scompenso CArdiaco) that, although primarily focused on the understanding of the interactions between hormones and chronic heart failure (CHF), is also aimed at developing more effective models of clinical care. We provide the scientific background and current stage of the project. In the context of a growing complexity of the patients' clinical management, the polipharmacy is a new arising challenge for clinicians, bearing direct economic, organizational and clinical implications. A better understanding, characterization and management of this issue represent an additional target of the TOSCA network

Biomarkers in Heart Failure: Clinical Insights

Heart failure (HF) is a clinical syndrome caused by structural and/or functional cardiac abnormalities and resulting from impaired cardiac output or an in-crease of intracardiac pressures at rest and/or during stress. Typical signs and symptoms of HF include ankle swelling, fatigue, dyspnea and peripheral edema, pulmonary crackles, or increased jugular venous pressure. Usually, patients with ejection fraction (EF) greater than or equal to 50% are defined as HF with preserved EF, where as those with EF less than 40% have HF with reduced EF. Patients with EF between 40% and 49% are now classified as HF with midrange EF

Presenting Systolic Blood Pressure and Outcomes in Patients With Acute Aortic Dissection

Background: Presenting systolic blood pressure (SBP) is a powerful predictor of mortality in many cardiovascular settings, including acute coronary syndromes, cardiogenic shock, and acute heart failure. Objectives: This study evaluated the association of presenting SBP with in-hospital outcomes, specifically all-cause mortality, in acute aortic dissection (AAD). Methods: The study included 6,238 consecutive patients (4,167 with type A and 2,071 with type B AAD) enrolled in the International Registry of Acute Aortic Dissection. Patients were stratified in 4 groups according to presenting SBP: SBP >150, SBP 101 to 150, SBP 81 to 100, or SBP ≤80 mm Hg. Results: The relationship between presenting SBP and in-hospital mortality displayed a J-curve association, with significantly higher mortality rates in patients with very high SBP (26.3% for SBP >180 mm Hg in type A AAD, 13.3% for SBP >200 mm Hg in type B AAD; p = 0.005 and p = 0.018, respectively) as well as in those with SBP ≤100 mm Hg (29.9% in type A, 22.4% in type B; p = 0.033 and p = 0.015, respectively). This relationship was mainly from increased rates of in-hospital complications (acute renal failure, coma, and mesenteric ischemia/infarction in patients with SBP >150 mm Hg; stroke, coma, cardiac tamponade, myocardial ischemia/infarction, and acute renal failure in patients with SBP ≤80 mm Hg). Notably, presenting SBP ≤80 mm Hg was independently associated with in-hospital mortality in both type A (p = 0.001) and type B AAD (p = 0.003). Conclusions: Presenting SBP showed a clear J-curve relationship with in-hospital mortality in patients with AAD. Although this association was related to increased rates of comorbid conditions at the edges of the curve, SBP ≤80 mm Hg was an independent correlate of in-hospital mortality

Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the T.O.S.CA. GHD Study.

BACKGROUND: Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD. METHODS: One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6±1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6±1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay. RESULTS: GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p = .008 and -24%, p = .015, respectively), lower LV end-systolic wall stress (-21%, p = .03), higher RV performance (+18% in RV area change, p = .03), lower estimated systolic pulmonary artery pressure (-11%, p = .04), higher peak VO2 (+20%, p = .001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p = .002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (β = -1.92, SE = 1.67, p = .03), VE/VCO2 slope (β = 2.23, SE = 1.20, p = .02) and NT-proBNP (β = 2.48, SE = 1.02, p = .016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p < .001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF. CONCLUSIONS: GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry

Background: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. Methods: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. Results: Compared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2). Conclusion: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT02335801

Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry

Aims Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. Methods The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid and Results hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37–2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28–3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01). Conclusion MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target