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Antonio Cittadini

Bio: Antonio Cittadini is an academic researcher from University of Naples Federico II. The author has contributed to research in topics: Heart failure & Medicine. The author has an hindex of 43, co-authored 164 publications receiving 7346 citations. Previous affiliations of Antonio Cittadini include Beth Israel Deaconess Medical Center & Seconda Università degli Studi di Napoli.


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Journal ArticleDOI
TL;DR: Evidence from laboratory models shows that GH induces mRNA expression for specific contractile proteins and myocyte hypertrophy, which provides plausible explanations for the cardiac abnormalities observed in clinical settings of excessive or defective GH production and support a role of GH in the maintenance of a normal cardiac structure and performance.
Abstract: GH exerts direct effects on myocardial growth and function. Evidence from laboratory models shows that GH (or IGF-I) induces mRNA expression for specific contractile proteins and myocyte hypertrophy. Furthermore, GH increases the force of contraction and determines myosin phenoconversion toward the low ATPase activity V3 isoform. These data provide plausible explanations for the cardiac abnormalities observed in clinical settings of excessive or defective GH production. In acromegaly, the functional consequences of GH excess initially prevail (hyperkinetic syndrome), followed by alterations of cardiac function when myocardial hypertrophy develops. This involves both ventricles and is purposeless because it occurs without increased wall stress. Hypertrophy also entails proliferation of the myocardial fibrous tissue that leads to interstitial remodeling. The functional consequence is an impaired ventricular relaxation that causes a diastolic dysfunction, followed by impairment of systolic function. In untreated disease, cardiac performance slowly but inexorably deteriorates and heart failure eventually develops. Several lines of evidence support the specificity of heart disease in acromegaly. Particularly demonstrative are the recent studies in which GH production was suppressed by octreotide, with a consequent significant regression of hypertrophy and improvement of cardiac dysfunction. It is not yet established whether full recovery of normal cardiac morphology and function is possible after correction of GH excess. The point is not a minor one since the possibility to revert, albeit partially, myocardial fibrosis is of great relevance to the control of cardiac hypertrophy in general. GHD leads to a reduced mass of both ventricles and to impaired cardiac performance with low heart rate (hypokinetic syndrome). These alterations are particularly evident during physical exercise and might provide an important contribution to the reduced exercise capacity of GHD patients, in addition to the reduced muscle mass and strength. The data also support a role of GH in the maintenance of a normal cardiac structure and performance. The hypokinetic syndrome is well documented in young patients in whom GHD began very early in their childhood. In contrast, the data in adult-onset GHD are less consistent. This suggests that the consequences of GHD are more relevant if the disorder starts during early heart development. As observed with other abnormalities associated with GHD, cardiac dysfunction is also susceptible to marked improvement by hrGH. This observation lends further support to the proposal to treat these patients with replacement therapy.

516 citations

Journal ArticleDOI
TL;DR: The results suggest that prolonged GH deficiency induces alterations in body composition and bone metabolism and density, and impairment of cardiac structure and function in adult life.
Abstract: The effects of recombinant GH doses (10 micrograms/kg.day, 3 times a week for 6 months) lower than those previously used in the treatment of GH-deficient adults (GHDA) on body composition, bone mineral content, and heart structure and function were investigated in seven (six males and one female, aged 25-27 yr) GHDA. They were studied before treatment, after treatment, and 6 months after stopping therapy, and findings were compared with those for 20 sex-, age-, and body mass index-matched healthy controls. Before treatment, GHDA showed a significant reduction in insulin-like growth factor-I levels, an increase in bioimpedance and fat mass percentage, a reduction of bone density at both distal and proximal sites, a decrease in bone Gla-protein and procollagen III levels, and significant cardiac impairment supported by a reduction of left ventricular mass index and left ventricular systolic function with decreased fractional shortening and rate-adjusted mean velocity of circumferential fiber shortening. GH treatment normalized insulin-like growth factor-I levels, body composition and echocardiographic findings, but not bone density. Six months after stopping therapy, all parameters investigated returned to the pretreatment conditions. Our results suggest that prolonged GH deficiency induces alterations in body composition and bone metabolism and density, and impairment of cardiac structure and function in adult life. GH replacement therapy for 6 months, despite the low doses used by us, is able to improve all previously impaired biochemical and clinical features, except for bone density. This improvement disappears 6 months after the withdrawal of therapy.

450 citations

Journal ArticleDOI
TL;DR: Echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease.
Abstract: Pulmonary arterial hypertension is most often diagnosed in its advanced stages because of the nonspecific nature of early symptoms and signs. Although clinical assessment is essential when evaluating patients with suspected pulmonary arterial hypertension, echocardiography is a key screening tool in the diagnostic algorithm. It provides an estimate of pulmonary artery pressure, either at rest or during exercise, and is useful in ruling out secondary causes of pulmonary hypertension. In addition, echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease.

394 citations

Journal ArticleDOI
TL;DR: It is indicated that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T4 substitutive therapy.
Abstract: Although subclinical hypothyroidism is frequently diagnosed, the decision to institute a substitutive therapy with L-T4 remains controversial. Because the cardiovascular system is considered a main target for the action of thyroid hormone, we investigated whether subclinical hypothyroidism induces cardiovascular abnormalities. Twenty-six patients (mean age, 36 +/- 12 yr) were evaluated by Doppler-echocardiography, whereas a subgroup of 10 patients, randomly selected, were reevaluated after 6 months of L-T4 substitutive therapy (mean dose, 68 microg daily). Thirty subjects (matched for age, sex, and body surface area) served as controls. Mean plasma TSH was significantly higher in patients (P < 0.001), whereas mean serum free T4 and free T3 concentrations, although in the normal range, were significantly lower (P < 0.001 and P < 0.005, respectively). Blood pressure and heart rate did not differ from control values. Echocardiogram examination showed no abnormalities of the left ventricular morphology and a slight, but not significant, reduction in the systolic function in the patient group. In contrast, Doppler-derived indices of diastolic function showed significant prolongation of the isovolumic relaxation time (94 +/- 13 vs. 84 +/- 8 msec; P < 0.001), increased A wave (55 +/- 13 vs. 48 +/- 9 cm/sec; P < 0.05), and reduced early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.4 +/- 0.3 vs. 1.7 +/- 0.3; P < 0.001). In the subgroup of 10 patients, thyroid hormone profile was normalized by 6 months of L-T4 substitutive therapy, whereas no changes were observed in the left ventricular morphology. Systolic function was significantly enhanced, as compared with pretreatment values (P < 0.01) but did not differ from control values. Also, systemic vascular resistance was significantly decreased by L-T4 replacement therapy. Assessment of diastolic function showed significant shortening of isovolumic relaxation time (77 +/- 15 vs. 91 +/- 8; P < 0.05), reduction of A wave (51 +/- 13 vs. 60 +/- 12; P < 0.01), and increase of early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.7 +/- 0.4 vs. 1.3 +/- 0.3; P < 0.001). These indices, however, were comparable with those of control subjects. These findings indicate that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T4 substitutive therapy.

322 citations

Journal ArticleDOI
TL;DR: Exogenous administration of GH and IGF-1 in the normal adult rat induces a cardiac hypertrophic response without development of significant fibrosis, and cardiac performance is increased both in vivo and in the isolated heart.
Abstract: Background Despite their increasing clinical use and recent evidence that growth hormone (GH) and insulin-like growth factor–1 (IGF-1) target the heart, there has been no systematic investigation of the effects of GH and IGF-1 on the cardiovascular system. Methods and Results Sixty normal but growing adult female rats were randomized to receive 4 weeks of treatment with GH (3.5 mg · kg−1 · d−1), IGF-1 (3 mg · kg−1 · d−1), a combination of the two, or placebo. Transthoracic echocardiograms were performed at baseline and at 2 weeks and 4 weeks of treatment. After the final echocardiography, rats underwent either closed-chest left ventricular (LV) catheterization or Langendorff perfusion studies. Myocyte diameter and interstitial tissue fraction were assessed by morphometric histology. Echocardiographic and ex vivo data demonstrated a LV hypertrophic response in all three groups of treated animals that was most marked in the GH group, which alone exhibited a concentric growth pattern (relative wall thickness...

286 citations


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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only and no commercial use is authorized.
Abstract: Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

4,285 citations

Journal ArticleDOI
TL;DR: The results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.
Abstract: Context: The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. Objective: To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. Design: Cross-sectional study.

2,525 citations

Journal ArticleDOI
TL;DR: It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how (poly)phenol molecules interact with human physiological and pathological processes.
Abstract: Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.

1,968 citations

Journal ArticleDOI
TL;DR: Changes in serum T( 3) levels in patients with chronic congestive heart failure are caused by alterations in thyroid hormone metabolism suggesting that patients may benefit from T(3) replacement in this setting.
Abstract: Thyroid hormone has many effects on the heart and vascular system.1 Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormone to alter cardiovascular hemodynamics.2 The hemodynamic effects of hypothyroidism are opposite to those of hyperthyroidism, although the clinical manifestations are less obvious. This review will integrate what is known about the mechanisms of thyroid hormone action on the heart2–5 with recent observations from both experimental and clinical studies of hyperthyroidism and hypothyroidism. We will also address the potential role of thyroid hormone treatment in patients with acute or chronic cardiac disease. Effects of . . .

1,862 citations