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Biomedical subjects

Maria Frigerio

Publications and source records attributed to Maria Frigerio.

At least 19 recordsLinked to original sources

Blood glutathione as independent marker of lipid peroxidation in heart failure.

BACKGROUND: Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated. AIM: To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients. METHODS: Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I-III). RESULTS: MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56-1.60) microM vs. 0.70 (0.40-0.83) microM, p=0.006]. Blood reduced GSH concentrations were significantly higher [662 (327-867) microM vs. 416 (248-571) microM, p=0.016], while alpha-tocopherol levels were significantly lower [15 (13-19) microM vs. 21 (17-32) microM, p=0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by MDA levels > or = 1.00 microM, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p=0.008), ischemic (OR 20, 95% CI 2.6 to 155, p=0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p=0.026). CONCLUSIONS: Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.

Adult↗

Programme to improve the use of beta-blockers for heart failure in the elderly and in those with severe symptoms: results of the BRING-UP 2 Study.

BACKGROUND: Beta-blockers are underused in HF patients, thus strategies to implement their use are needed. OBJECTIVES: To improve beta-blocker use in elderly and/or patients with severe heart failure (HF) and to evaluate safety and outcome. METHODS: Patients with symptomatic HF and age>/=70 years or left ventricular EF<25% and symptoms at rest were enrolled, including those already on beta-blocker treatment. Patients who were not receiving a beta-blocker were considered for carvedilol treatment. All patients were followed up for 1-year. RESULTS: Of the 1518 elderly patients, 505 were already on beta-blockers, and carvedilol was newly prescribed in 419 patients. At 1-year, patients treated with carvedilol had a lower incidence of death [10.8% vs. 18.0% in already treated (adjusted RR 0.68; 95%CI 0.49-0.96) and 11.2% in newly treated patients (adjusted RR 0.68; 95%CI 0.48-0.97)]. Of the 709 patients with severe HF, 38.4% were already on beta-blockers, and carvedilol was newly prescribed in 189 patients. Patients not treated with carvedilol showed the worst clinical outcome. Total rate of discontinuation (including adverse reaction and non-compliance) was 14% and 9%, respectively, in elderly and severe patients. CONCLUSIONS: In a real world setting, beta-blocker treatment was not associated with an increased risk of adverse events in elderly and severe HF patients.

Adrenergic beta-Antagonists↗

Left ventricular mechanical support with the Impella Recover left direct microaxial blood pump: a single-center experience.

The Impella Recover left direct (LD) is a new intravascular microaxial blood pump, intended as a short-term mechanical support especially in case of acutely reduced left ventricular function. From September 2002 to October 2004, Impella was used to support 12 patients: six patients were supported as bridge-to-heart transplant (HTx); three patients were treated for fulminant acute myocarditis, and three patients for postcardiotomy low-output syndrome. Mean support time was 8.8 +/- 2.3 days. Overall mortality was 50%. Four patients were successfully HTxed; two patients supported as bridge-to-HTx died on left ventricular assist device. Two patients with myocarditis died of septic shock; two patients in the group of postcardiotomy died of multiorgan failure. The latter two patients were slowly weaned from the device, and at 3-months follow-up showed good improvement of the left ventricular function. Our initial experience with Impella Recover LD as mechanical support for patients in cardiogenic shock of various etiology is promising, yielding a good survival in a population of particularly compromised patients.

Adolescent↗

[Prognostic value of serial measurements of left ventricular function and exercise performance in chronic heart failure].

INTRODUCTION AND OBJECTIVES: The prognostic value of a single measurement of ejection fraction and peak oxygen uptake in chronic heart failure has been extensively investigated. The aim of our study was to evaluate the prognostic significance of serial changes in ejection fraction and exercise performance in moderate to severe chronic heart failure. METHODS: 182 patients (156 men, 53 [47-58] years) underwent echocardiography and cardiopulmonary exercise testing at baseline and after 10 [8-12] months. Most patients had idiopathic dilated cardiomyopathy (69%) and all patients presented left ventricular ejection fraction <45%. Median follow-up was 21 [14-34] months; cardiac death and heart transplantation were the end-points. Hazard ratio (HR, per unit) is presented with its 95% confidence interval (CI). RESULTS: During follow-up 18 patients (9.9%) died and 14 (7.7%) underwent heart transplantation. Baseline ejection fraction (HR, 0.94, 95% CI, 0.89-0.98 P=.006) and mitral regurgitation (HR, 4.22, 95% CI, 1.63-10.92, P=.003), and delta (second examination-baseline) ejection fraction (HR, 0.93, 95% CI, 0.88-0.98, P=.01) were the only significant variables at univariate analysis. Both ejection fraction and delta ejection fraction remained independently associated with events at multivariate analysis. The prognostic power significantly increased between a model including ejection fraction alone and another one including ejection fraction plus delta ejection fraction. CONCLUSIONS: In clinically stable patients with chronic heart failure, ejection fraction and its changes were independently associated with outcome; on the contrary, serial cardiopulmonary exercise testing did not provide significant prognostic value. Baseline plus changes in ejection fraction showed better prognostic performance than baseline ejection fraction alone.

Chronic Disease↗

Bridge to transplantation with the MicroMed DeBakey ventricular assist device axial pump: a single centre report.

OBJECTIVE: Left ventricular assist devices (VADs) are an accepted therapy to bridge patients with end-stage heart failure to heart transplantation. The DeBakey VAD, a continuous axial flow pump weighing 93 g, has been introduced into clinical practice as a bridge to transplant. METHODS: Starting from April 2000,17 patients (12 males, five females, mean age 44.3 +/- 12.8 years; 11 dilated idiopathic cardiomyopathy, five ischaemic cardiomyopathy, one pulsatile device failure) with end-stage heart failure were implanted with a DeBakey VAD as a bridge to transplantation at our institution. Before implant, all patients suffered from severe heart failure (New York Heart Association functional class IV) despite optimal medical therapy and were put on the waiting list for heart transplantation. Mean cardiac index was 1.59 +/- 0.51 l/min/m2. RESULTS: Fourteen patients were successfully transplanted after 99 +/- 117 days of assistance (range 11-443 days). Two patients died during assistance of multiorgan failure, one patient is still on VAD. No patient needed additional right ventricular mechanical support. Left ventricular/left VAD thrombosis occurred in one patient who was successfully treated conservatively. No clinical elevation of plasma free haemoglobin was detected. Neither device, driveline, abdominal pocket infection nor device failure occurred. CONCLUSIONS: In our experience with the continuous axial flow DeBakey VAD, a high success rate was obtained associated with a low risk of complications. All the patients tolerated continuous blood flow for extended periods that makes this device a valuable alternative to pulsatile VADs as a bridge to transplantation.

Adult↗

[Mechanical assist devices in advanced heart failure. Indications and perspectives].

Congestive heart failure is recognized as a major public health issue and is the leading cause of death in western countries. Heart transplantation currently remains the gold standard option for end-stage heart failure patients. Heart transplantation is also one of the most limited therapies, not only with regard to the lack of donor hearts but also because of the surgical limitations inherent to the clinical aspects of this severely ill patient population. Mechanical circulatory support systems have been developed as effective adjuvant therapeutic options in these terminally ill patients. Over the past two decades, mechanical circulatory support devices have steadily evolved in the clinical management of end-stage heart failure, and have emerged as a standard of care for the treatment of acute and chronic heart failure refractory to conventional medical therapy. Future blood pumps should be smaller and totally implantable, as well as more efficient, biocompatible, and reliable.

Heart Failure↗

Different clinical scenarios for circulatory mechanical support in acute and chronic heart failure.

Chronic heart failure (HF) is a leading cause of death in developed countries. Over the last 2 decades, mechanical circulatory support (MCS) devices have steadily evolved in the clinical management of end-stage HF and have emerged as a standard of care for the treatment of acute and chronic HF refractory to conventional medical therapy. Possible indications for using MCS are acute cardiogenic shock, as a bridge to transplantation, as a bridge to recovery, and more recently, as destination therapy in dilated cardiomyopathy, of either ischemic or idiopathic etiology. We reviewed the different clinical scenarios in which we think there are currently indications to implant different kinds of MCS systems.

Acute Disease↗

Drugs for left ventricular remodeling in heart failure.

Left ventricular (LV) remodeling (ie, enlargement and functional deterioration occurring over time) is among the main mechanisms of progression in heart failure (HF). LV dilatation and dysfunction are major negative prognostic markers in patients with HF. Treatments that are effective in limiting or even reversing this process can be expected to provide clinical benefit. Changes in LV dimensions rather than in ejection fraction should be used to monitor remodeling. Ejection fraction can be influenced by transient loading conditions and by agents that stimulate contractility at the expense of increased oxygen demand, whereas dimensional changes probably reflect structural modifications occurring in the myocardium. The neurohormonal antagonists that have been demonstrated to reduce mortality and morbidity in HF (angiotensin-converting enzyme inhibitors [ACE], beta-blockers, angiotensin receptor blockers, and aldosterone antagonists) are also able to inhibit or reverse remodeling. In reverse remodeling, beta-blockers appear to be superior to the other classes of drugs, with a stronger correlation between dose and effect, but it must be remembered that they have been tested as an addition to background therapy that may include ACE inhibitors. With regard to nonpharmacologic strategies, biventricular pacing is associated with functional improvement and reverse remodeling in patients with advanced HF and electromechanical dyssynchrony, and it recently has been demonstrated to improve survival in a randomized clinical trial.

Adrenergic beta-Antagonists↗

Different applications for left ventricular mechanical support with the Impella Recover 100 microaxial blood pump.

The "Impella Recover 100" (IR100) is a new intravascular microaxial blood pump for use as short-term mechanical support for cases of acutely reduced left ventricular function. From September 2002 to April 2003, we used the IR100 to support 5 patients: 2 patients were bridged to heart transplant; 2 were being treated for fulminant acute myocarditis; and 1 for post-cardiotomy low-output syndrome. Only 1 patient with myocarditis died of septic shock, 2 had successful heart transplants; and the latter 2 were slowly weaned from the device and, at 3-month follow-up, showed moderate improvement of left ventricular (LV) function. Our initial experience with the IR100 as mechanical support for patients in cardiogenic shock of varying etiology has been positive, yielding good survival in a population of particularly compromised patients.

Acute Disease↗

Blood glutathione as a marker of cardiac allograft vasculopathy in heart transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV. METHODS: Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis. RESULTS: CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008). CONCLUSIONS: In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.

Biomarkers↗

One-year clinical experience with the Acorn CorCap cardiac support device: results of a limited market release safety study in Italy and Sweden.

BACKGROUND: The Acorn CorCap cardiac support device (CSD) is a mesh-like device intended to provide end-diastolic support and reduce ventricular wall stress. Animal studies with the CorCap CSD have demonstrated beneficial reverse remodeling, and preliminary safety studies in patients with heart failure have shown that the device is safe and associated with improved left ventricular (LV) structure and function. The objective of the current study was to further evaluate the safety and efficacy of the CorCap CSD in patients with advanced heart failure. METHODS: Twenty-four patients with dilated cardiomyopathy, severe LV dysfunction, and advanced heart failure (NYHA class II-IV) were enrolled at four centers in Italy and Sweden. All patients underwent CorCap CSD implantation either alone (n = 3) or in combination with mitral valve repair/replacement (n = 13), coronary artery bypass surgery (n = 6), combined mitral valve repair/coronary artery bypass surgery (n = 1) or aneurysmectomy (n = 1). RESULTS: The LV end-diastolic diameter decreased from 69.3 +/- 7.2 to 60.1 +/- 9.0 mm at 3 months, 60.9 +/- 9.6 mm at 6 months, and 58.9 +/- 8.0 mm at 12 months (all p < 0.05). A trend toward an improved LV ejection fraction (28.8 +/- 10.5% at baseline and 32.4 +/- 12.7, 33.1 +/- 10.8, and 33.8 +/- 13.9% at 3, 6 and 12 months respectively) was also noted. The NYHA functional class, 6-min walking distance, and quality of life as measured using Uniscale were all improved. There were no differences in response among the patients submitted to the different types of concomitant surgery. CONCLUSIONS: In agreement with earlier safety studies, even the present investigation demonstrated improvements in cardiac structure and function as well as in patient functional status after Cor Cap CSD implantation. Randomized controlled trials are in progress.

Adult↗

[Use of imaging in the evaluation of heart transplant recipients].

Common complications after heart transplantation include acute rejection and coronary allograft vasculopathy. In order to detect the presence of rejection, tissue Doppler imaging echocardiography provides high accuracy and allows to optimize the timing of endomyocardial biopsies, which remain the cornerstone in rejection diagnosis. Coronary allograft vasculopathy is often a diffuse disease so that it is difficult to recognize by imaging modalities, such as myocardial perfusion scintigraphy, which are based on intra-patient comparison of different areas. Quantitative assessment of the myocardial blood flow by positron emission tomography overcomes this issue. Dobutamine stress echocardiography provides accurate diagnosis as well as useful prognostic information. Nevertheless, intracoronary ultrasound is nowadays considered the gold standard for vasculopathy assessment, since it is able to detect a minimum intimal thickening which represents the early feature of disease. Magnetic resonance represents the most attractive approach, though it has not yet gained widespread clinical use.

Acute Disease↗

Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.

Adult↗

Fulminant myocarditis during HIV seroconversion: recovery with temporary left ventricular mechanical assistance.

A 32-year-old male was admitted to our intensive care unit for low cardiac output syndrome. Echocardiography was suggestive of extensive hypokinesia and the ejection fraction was 0.22. Serological tests, including anti-HIV antibodies (ELISA), were negative. The patient was intubated and an intra-aortic balloon pump was inserted. Twenty-four hours after admission a paracorporeal left ventricular assist device (LVAD-MEDOS) was implanted. The left ventricular function showed progressive improvement with normalization of the ejection fraction on day 19. The device was removed on day 20. Before discharge, the patient admitted that he had had unprotected sex with numerous male acquaintances; anti-HIV testing turned positive. The final diagnosis was fulminant myocarditis during HIV seroconversion.

Adult↗

Diastolic heart failure.

Diastolic heart failure is characterized by the presence of heart failure with preserved left ventricular ejection fraction (LVEF): documentation of diastolic dysfunction, usually by Doppler echocardiography, is strongly recommended. Heart failure with preserved LVEF is a heterogeneous and common condition, especially in the elderly, among whom represents up to 50% of all heart failure patients. Mortality is generally lower than in patients with heart failure and low LVEF, and depends on etiology, patient conditions, and comorbidities. Anyway, morbidity is very high. So far, treatment of diastolic heart failure is empirical, and is aimed to maintain cardiac output, reduce filling pressure, control heart rate and rhythm, and antagonize disease progression with diuretics, inhibitors of the renin-angiotensin-aldosterone system, nitrates, and digoxin.

Diastole↗

Usefulness of chronotropic incompetence to dipyridamole in predicting myocardial perfusion defects in heart transplant recipients.

The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.

Case-Control Studies↗

Prevention and management of chronic heart failure in management of asymptomatic patients.

Symptomatic heart failure is preceded by a somewhat prolonged asymptomatic stage in many patients. The number of patients with asymptomatic heart dysfunction is about 4-fold greater than the number of patients with clinically overt heart failure. Pharmacologic treatment with angiotensin-converting enzyme inhibitors and beta-blockers (in particular carvedilol) of asymptomatic patients with systolic left ventricular (LV) dysfunction can prevent or delay the occurrence of symptoms and reduce mortality in the long term. Thus, it would be of utmost importance to recognize and appropriately treat these patients before they develop heart failure symptoms. The cost-effectiveness of screening for asymptomatic heart dysfunction in the general population and in cohorts at risk has not been extensively evaluated. A normal electrocardiogram has a high negative predictive value in patients at risk. Echocardiography is the best tool for diagnosis and characterization of heart dysfunction, but extensive use is limited by availability and cost. Natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) are very sensitive markers of heart dysfunction and volume overload, and their measurement has been proposed as a first-line test to select patients who need echocardiography. The definition of the etiology of LV dysfunction--in particular, of the ischemic etiology--has prognostic and therapeutic implications. In addition to revascularization, pharmacologic treatment with antiplatelets and statins is helpful in preventing new ischemic events and the development of heart failure. The prevention, or at least the delay, of clinical manifestations of heart failure is strongly related to an effective approach to the asymptomatic stage. Therefore, it is important to educate the entire medical community, particularly physicians in the primary care setting, about recognition and treatment of these patients.

Chronic Disease↗