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Stress ossidativo ed infiammazione: basi fisiopatologiche per un nuovo approccio terapeutico nello scompenso cardiaco. Risultati di due trials randomizzati, controllati con placebo.
No full textIntroduzione: Lo scompenso cardiaco (SC) si definisce come una complessa condizione fisiopatologica di cronico deterioramento dei meccanismi ossidativi. In pazienti con SC cronico le concentrazioni sieriche di acido urico sono frequentemente elevate e l’iperuricemia riflette un’alterazione del metabolismo ossidativo ed iperattivazione dell’enzima xantina ossidasi (XO). Uno studio clinico recente evidenzia una forte correlazione tra acido urico e parametri ecocardiografici di disfunzione diastolica, condizione di frequente riscontro in pazienti con cardiomiopatia dilatativa e associata a prognosi peggiore. Lo SC, inoltre, rappresenta uno stato infiammatorio caratterizzato da iperproduzione di citochine pro-infiammatorie implicate nella patogenesi di alcuni aspetti tipici dello SC, quali l’edema polmonare acuto. Pregressi studi hanno evidenziato effetti benefici del trattamento con statine in fase di stabilità clinica di questa patologia.
Scopo: valutare se l’inibizione della XO con allopurinolo possa influire sulle proprietà diastoliche del miocardio e sui livelli sierici di NT-proBNP in un gruppo di pazienti con SC cronico (Studio di SC cronico); valutare l’effetto del trattamento precoce con statine sul rimodellamento ventricolare sinistro e sui sintomi in un gruppo di pazienti con SC acuto (Studio di SC acuto).
Metodi: (Studio di SC cronico): sono stati arruolati 53 pazienti con scompenso cardiaco secondario a cardiomiopatia dilatativa in condizioni cliniche stabili e terapia medica ottimale da almeno 3 mesi e randomizzati in doppio cieco ad allopurinolo 300 mg/die (A), o placebo (P) per 3 mesi. I pazienti sono stati sottoposti ad una valutazione clinica ed ecocardiografico completa all’inizio ed al termine del periodo di trattamento. (Studio di SC acuto): 61 pazienti con disfunzione ventricolare sinistra, ricoverati per episodio di SC acuto, sono stati randomizzati in doppio cieco ad atorvastatina 20mg/die (A), o placebo (P) per 3 mesi. Ciascun paziente è stato sottoposto a prelievo per ematochimici, valutazione clinica ed esame ecocardiografico completo all’inizio, ad una settimana ed al termine del periodo di studio.
Risultati: (Studio di SC cronico): l’età media era 66±10; la classe NYHA era 2.2±0.6; i livelli sierici medi di acido urico erano 400±100mmol/L. Al termine del trimestre di trattamento i livelli sierici di NT-proBNP si sono ridotti nel gruppo A (-191±583 mmol/L, p=0.0004), con un significativo effetto terapeutico (p=0.0033), mentre non si sono modificati nel gruppo P. E’ stata riscontrata un riduzione significativa della velocità dell’onda E mitralica nel gruppo A (0.6±0.2 vs. 07±0.2 m/s, p=0.01), ma non nel gruppo P ed il rapporto E/E’ è migliorato nel gruppo A (10.7±6.7 vs. 15.1±11.8), mentre è rimasto stabile nel gruppo P, con un significativo effetto terapeutico per entrambi (p=0.01 and p=0.02 rispettivamente). (Studio di SC acuto): all’inizio dello studio le caratteristiche cliniche ed ecocardiografiche non differivano nei 2 gruppi di pazienti (età media 72±7 anni gruppo P; 68±12 anni gruppo A; Colesterolo 3.6±1 mmol/L gruppo P; 3.5±1.3 mmol/L gruppo A; FE 29±7 % gruppo P; 25±6 % gruppo A). Al follow up la classe NYHA e lo score di congestione sono migliorati in entrambi i gruppi, tuttavia maggiormente ed in assenza di un peggioramento della funzione renale nel gruppo A. Si è evidenziata una riduzione dei volumi ventricolari, in particolare del volume tele-sistolico ( 3 mesi 26 ml; p=0.001) e la FE ( 3 mesi: -5; p=0.0005) è migliorata solamente nel gruppo A. Infine nello stesso gruppo è emersa una riduzione significativa del volume atriale sinistro ( 3 mesi: 12.7 ml; p=0.05) ed i parametri di funzione diastolica sono migliorati.
Conclusioni: in pazienti con SC il trattamento con allopurinolo in aggiunta alla terapia medica ottimale per tre mesi, apporta un beneficio significativo sui parametri di funzione diastolica ventricolare ed il suo utilizzo correla con una riduzione statisticamente significativa del NT-proBNP. Il trattamento precoce con statina in pazienti con SC acuto migliora i sintomi e influisce sul processo di rimodellamento ventricolare sinistro migliorando FE e riducendo i volumi.Background: Heart failure (HF) is a complex pathophysiological condition of chronic deterioration of oxidative mechanisms. Hyperuricemia, a common finding in this context, reflects the degree of oxidative stress. It has been previously shown that diastolic dysfunction, which is frequently observed in patients with dilated cardiomyopathy and is associated with poor prognosis, relates to serum uric acid levels. Furthermore, HF represents an inflammatory state characterized by overproduction of pro-inflammatory cytokines involved in the pathogenesis of some typical aspects of HF, such as pulmonary oedema. Previous studies showed positive effects of statin treatment in a stable phase of the disease.
Aim of the project: to determine whether inhibition of XO with allopurinol might affect diastolic function and NT-proBNP levels in a group of patients with chronic HF (Chronic HF Study); to evaluate the effects of statin therapy on left ventricular (LV) remodeling and symptoms in a group of subjects in the early stage of acute HF (Acute HF Study).
Methods: Chronic HF study: 53 stable chronic HF outpatients with LV systolic dysfunction on optimal background therapy and clinically stable for at least three months, were randomly assigned to receive allopurinol (A), 300 mg/day, or placebo (P) for three months, in a double-blind trial. Every patient underwent a complete clinical and echocardiographic evaluation at baseline and at the end of the study. Acute HF study: 61 patients, admitted to our clinic for acute HF episode, with left ventricular dysfunction, were randomized to receive Atorvastatin (A) 20 mg/day or placebo (P) for three months, in a double-blind trial. A biochemical and clinical examination and a complete echocardiogram was performed for each patient at baseline, at one week and at the end of the study period.
Results: Chronic HF study: mean age was 66±10 years and mean NYHA class was 2.2±0.6; mean serum uric acid levels were 400±100 mmol/L. At follow-up, in the allopurinol group there was a significant reduction in NT-proBNP levels compared with baseline (-191±583 mmol/L, p=0.0004), while no significant difference was observed in the placebo group, with a significant treatment effect (p=0.0033). In the allopurinol group there was a significant reduction of mitral E wave velocity (E) (0.6±0.2 vs. 07±0.2 m/s, p=0.01), and of the ratio between E and the velocity of early myocardial lengthening (E’) (10.7±6.7 vs. 15.1±11.8), but no significant changes of these two parameters in the placebo group, with a significant treatment effect for both (p=0.01 and p=0.02, respectively). Acute HF study: the two groups did not differ in clinical and echocardiographic baseline characteristics (mean age 72±7 years group P; 68±12 years group A; Colesterol 3.6±1 mmol/L group P; 3.5±1.3 mmol/L group A; EF 29±7 % group P; 25±6 % group A). At follow up NYHA class and congestion score improved in both groups, however more and without worsening of renal function in group A. There was a reduction in LV volumes, in particular in end-systolic volume ( 3 months 26 ml; p=0.001) and EF improved ( 3 months: -5; p=0.0005) only in the Atovarstatin group. Furthermore, in the same group there was a reduction of left atrium volume ( 3 months: 12.7 ml; p=0.05) and diastolic parameters improved.
Conclusions: in CHF patients, the addition of allopurinol on top of optimal medical therapy for three months significantly improves echocardiographic parameters of diastolic function and lowers NT-proBNP levels. Early statin treatment in acute HF patients improves symptoms and affects cardiac remodeling by improving EF and reducing LV volumes
Irreversible left atrium dilatation preceding left ventricular dysfunction during trastuzumab therapy
No full textIrreversible left atrium dilatation preceding left ventricular dysfunction during trastuzumab therap
American Diabetes Association - 75th Scientific Meeting; Section: Epidemiology/Genetics; Poster n. 1581-P: "Nonalcoholic Fatty Liver Disease Is Associated with Heart Valve Calcification in Type 2 Diabetes"
No full textAortic valve sclerosis (AVS) and mitral annulus calcifi cation (MAC) are powerfulpredictors of adverse cardiovascular outcomes in patients with type 2diabetes (T2D), but the aetiology of valvular calcifi cation is uncertain. Nonalcoholicfatty liver disease (NAFLD) is an emerging cardiovascular risk factorcommonly present in T2D patients, but its association with valvular calcifi -cation is unknown. We sought to investigate whether NAFLD is associatedwith AVS and/or MAC in T2D patients. We conducted a cross-sectional studyby performing a conventional echocardiography and liver ultrasonography ina sample of 247 consecutive outpatients with T2D (179 men; mean age 68years) free of known liver diseases, prior history of chronic heart failure andmoderate-to-severe valvular heart disease. Overall, 139 (56.3%) patients hadno calcifi cation at both aortic and mitral valve (HVC-0), 65 (26.3%) had onevalve affected (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). NAFLD was present in 175 (70.8%) patients and its prevalence markedlyincreased in patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1%vs. 83.1% vs. 60.4%, respectively; p<0.001). NAFLD was associated with AVSand/or MAC (unadjusted-odds ratio [OR] 3.51, 95% CI 1.89-6.51, p<0.001). Adjustmentsfor age, sex, smoking history, alcohol consumption, diastolic bloodpressure, hemoglobin A1c, LDL-cholesterol, estimated glomerular fi ltrationrate, use of hypoglycemic, lipid-lowering and anti-hypertensive medicationsand echocardiographic variables did not substantially attenuate the strong associationof NAFLD with AVS and/or MAC (adjusted-OR 2.97, 95% CI 1.31-6.70,p<0.01). In conclusion, these results show for the fi rst time that NAFLD is astrong and independent predictor of cardiac calcifi cation in both aortic andmitral valves in patients affected by T2D. Further research is needed to betterelucidate the mechanisms underlying this association
Hyperuricemia is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes
No full textHyperuricemia/gout and atrial fibrillation (AF) are two pathological conditions that are highly prevalent in type 2 diabetes and share multiple cardiovascular risk factors. However, the relationship between elevated levels of serum uric acid and risk of AF in type 2 diabetes is currently poorly known
Early functional and structural changes of the left atrium in a patient with trastuzumab: related cardiotoxicity
No full textbreast cancercancer, growthcancer, therapy cardiotoxicity, cardiovascular parameters, dyspnea, Echocardiography, heart failure, heart left ventricle ejection fraction , heart left ventricle mass, heart ventricle remodeling, hemodynamics ,human, left atrial volume, Letter, mastectomy, metastasis, mitral valve regurgitation, overall survival, peak atrial longitudinal, progression free survival, speckle tracking echocardiography, survival rat
Influence of Myocardial Fibrosis on Left Ventricular Hypertrophy in Patients with Symptomatic Severe Aortic Stenosis
Full text linkAim: It was the aim of our study to determine whether myocardial fibrosis influences physiologic or non-physiologic left ventricular (LV) hypertrophy in severe aortic stenosis. Methods: Myocardial fibrosis was evaluated using specimens taken from the ventricular septum in 79 patients submitted to aortic valve replacement because of symptomatic aortic stenosis. Patients were considered to have physiologic LV hypertrophy if end-systolic wall stress, evaluated by echocardiography, was 90 kdyn/cm(2) were considered to have non-physiologic hypertrophy. Results: Fibrosis tissue mass index was significantly inversely related with LV fractional shortening and directly related with LV diastolic and systolic diameter and LV mass index (LVMI). Patients with non-physiologic hypertrophy (n = 24) had a higher LVMI due to larger LV diastolic and systolic diameters with thinner wall, resulting in lower relative wall thickness. These patients had a higher fibrosis tissue mass index and impaired LV systolic and diastolic functions, as suggested by lower LV fractional shortening and higher mean wedge pressure. At follow-up of 7.4 ± 2.1 months, the LVMI and New York Heart Association class remained higher in patients with non-physiologic hypertrophy. Conclusions: Our study suggests a different quality of hypertrophies in patients with aortic stenosis, where myocardial fibrosis seems to be the critical abnormality that differentiates adaptive from maladaptive response to increased afterload
Impaired Aortic Valve Growth in Type 1 Diabetes Mellitus
No full textThe study have evaluated the differences in aortic valve dimensione between type 1 diabetic patients and control subjects. As reported in Table 1, females affected by type 1 diabetes showed an aortic annulus diameter of 9.9 0.9 mm/m2 compared with 11.7 1.1 mm/m2 in female controls (P < 0.01), whereas diabetic males presented a diameter of 10.1 1.1 mm/m2 compared with 11.9 1.4 mm/m2 (P < 0.01) in male controls. Interestingly, men with type 1 diabetes showed a significantly lower aortic annulus diameter than female controls. Moreover, when we compared subjects with the onset of diabetes earlier than 10 years of age (n 1⁄4 31) and then compared them with those with the onset of the disease later than 22 years of age (n 1⁄4 19), a tendency towards a lower annulus diameter in patients with an early onset of diabetes (9.8 0.9 vs 10.6 1.1 mm/m2 , respectively; P 1⁄4 0.07) was observed
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Role of Speckle Tracking Echocardiography in the Evaluation of Breast Cancer Patients Undergoing Chemotherapy: Review and Meta-analysis of the Literature
No full textDiagnosis and management of Cancer therapeutics-related cardiac dysfunction is of crucial importance in breast cancer (BC) patients. The role of advanced echocardiographic techniques, such as deformation imaging, in the diagnosis and characterization of patients receiving cancer therapy has so far involved relatively small studies in the research setting. Therefore, we conducted a meta-analysis and systematic review of observational studies evaluating myocardial changes during chemotherapy detected through conventional echocardiographic parameters, such as 2D left ventricular ejection fraction (2D LVEF), and 2D Speckle tracking echocardiography (STE). The literature search retrieved 487 research works, articles, of which 17 were found to be pertinent with this topic. After full article review, 16 studies were considered suitable for the present analysis. Two separate analyses, one for the anthracyclines-based therapeutic regimen and one for the trastuzumab based therapeutic regimen, were performed. A significant reduction in 2D LVEF and 2D STE parameters during cancer therapy was found in both the investigations. Peak systolic global longitudinal strain demonstrated to be the most consistent 2D STE parameter in detecting early myocardial changes among all the studies. Thus, we confirmed the role of 2D STE for the early detection of myocardial damage, suggesting its crucial role in monitoring BC patients and eventually driving the introduction of cardioprotective treatment
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