Carlo Campana - Academia.edu (original) (raw)

Papers by Carlo Campana

Research paper thumbnail of Clinically Significant Drug Interactions with Cyclosporin

Clinical Pharmacokinetics, 1996

Research paper thumbnail of In-hospital Heart Rate Reduction With Beta Blockers and Ivabradine Early After Recovery in Patients With Acute Decompensated Heart Failure Reduces Short-Term Mortality and Rehospitalization

Frontiers in Cardiovascular Medicine, 2021

Objective: In the past years, heart rate (HR) has emerged as a highly relevant modifiable risk fa... more Objective: In the past years, heart rate (HR) has emerged as a highly relevant modifiable risk factor for heart failure (HF) patients. However, most of the clinical trials so far evaluated the role of HR in stable chronic HF cohorts. The aim of this multi-center, prospective observational study was to assess the association between HR and therapy with HR modulators (beta blockers, ivabradine, or a combination of ivabradine and beta blockers) at hospital discharge with patients' cardiovascular mortality and re-hospitalization at 6 months in acutely decompensated HF patients.Materials and Methods: We recruited 289 HF patients discharged alive after admission for HF decompensation from 10 centers in northern Italy over 9 months (from April 2017 to January 2018). The primary endpoint was the combination of cardiovascular mortality or re-hospitalizations for HF at 6 months.Results: At 6 months after discharge, 64 patients were readmitted (32%), and 39 patients died (16%). Multivariat...

Research paper thumbnail of Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry

Circulation, Jan 15, 2018

Background-There is controversy regarding outcome of patients with acute myocarditis (AM), and la... more Background-There is controversy regarding outcome of patients with acute myocarditis (AM), and lack of data 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 multi-center 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 and those older than 50 years without coronary angiography were excluded. The final study population comprised 443 patients (median age 34 years, 19.4% female) with AM diagnosed either by endomyocardial biopsy (EMB) or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance (CMR). Results-At presentation, 118 patients (26.6%) had either left ventricular (LV) ejection fraction (EF) <50%, sustained ventricular arrhythmias (VA) or a low cardiac output syndrome (LCOS) whilst 325 (73.4%) had no such complications. EMB was performed in 56/443 (12.6%), and a baseline CMR was performed in 415/443 (93.7%) of patients. Cardiac mortality plus heart transplant (HTx) at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus HTx 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 (post-discharge death and HTx, sustained VA treated with electrical shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at 5-year follow up, with a higher incidence in patients with complicated forms (10.8% vs. 0% in uncomplicated AM, Log-rank p<0.0001). Beta adrenoceptor blockers were the most frequently employed 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 CMR and 8/55 (14.5%) with complications at presentation had LVEF<50% compared with 1/145 (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 LVEF<50%, VA or LCOS at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent LV systolic dysfunction.

Research paper thumbnail of Pulmonary hypertension: classification and diagnostic algorithm

Italian heart journal : official journal of the Italian Federation of Cardiology, 2005

Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progre... more Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and premature death. Recently, the diagnostic approach has been more clearly defined according to the new clinical classification and with consensus reached on algorithms of various investigative tests and procedures that exclude other causes and ensure an accurate diagnosis of PAH. The diagnostic procedures include clinical history and physical examination, ECG, chest X-ray, transthoracic Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, ventilation and perfusion lung scan, high-resolution computed tomography of the lungs, contrast-enhanced spiral computed tomography of the lungs and pulmonary angiography, blood tests and immunology, abdominal ultrasound scan, exercise capacity assessment, and hemodynamic evaluation. Invasive and non-invasive markers of disease severity, e...

Research paper thumbnail of Infusion therapy in severe heart failure. A reappraisal

Italian heart journal : official journal of the Italian Federation of Cardiology, 2003

Decompensated heart failure is associated with high rates of morbidity and mortality and it is re... more Decompensated heart failure is associated with high rates of morbidity and mortality and it is responsible for numerous hospitalizations. The current approach to acute exacerbations is based on diuretics, vasodilators and inotropes. Compared with the impressive development of new therapeutic agents designed for other cardiovascular diseases, little progress has been observed in developing new drugs for the treatment of decompensated heart failure. Moreover, a series of controlled clinical trials failed to show a better outcome or a reduction in morbidity during treatment with inotropes, even though promising results were recently observed in controlled clinical trials with new classes of drugs, such as calcium sensitizers and nesiritide; these agents will probably modify the treatment options of decompensated heart failure in the coming years.

Research paper thumbnail of Coexistence of mitochondrial DNA and beta  myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure

Heart, 1998

Objective-To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patie... more Objective-To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with myosin heavy chain (MHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. Design-Molecular analysis of MHC and mtDNA gene defects in patients with HCM. Setting-Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy. Patients-Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional aVected patients and 27 unaVected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included an additional 27 patients with HCM and 102 with dilated cardiomyopathy. Intervention-Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens. Main outcome measures-Screening for mutations in MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing. Results-One proband (kindred A) (plus seven aVected relatives) had arginine 249 glutamine (Arg249Gln) MHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel MHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and B) were identical, but diVerent from those of the two patients with Lys450Glu plus T9957C(Phe->Leu) mutations (kindred C). Cytochrome C oxidase activity and histoenzymatic staining were severely decreased in the two patients in kindreds A and B, but were unaVected in the two in kindred C. Conclusions-MHC gene and mtDNA mutations may coexist in patients with HCM and end stage congestive heart failure. Although MHC gene mutations seem to be the true determinants of HCM, both mtDNA mutations in these patients have known prerequisites for pathogenicity. Coexistence of other genetic abnormalities in MHC linked HCM, such as mtDNA mutations, may contribute to variable phenotypic expression and explain the heterogeneous behaviour of HCM.

Research paper thumbnail of Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy

Cardiovascular ultrasound, Jan 25, 2003

It has been suggested that an extensive contractile reserve identified recognised by means of dob... more It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. We studied 26 patients (21 males and five females) with a mean age of 58 PlusMinus; 10 years: 11 were not receiving beta-blockers...

Research paper thumbnail of Design of the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study to assess the ability of remote monitoring to treat and triage patients more effectively

Trials, 2009

Background: Heart failure patients with implantable defibrillators (ICD) frequently visit the cli... more Background: Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier. Methods: The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink ® monitor for remote transmission or the conventional method of inperson evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations.

Research paper thumbnail of Intermittent haemodiafiltration in refractory congestive heart failure: BNP and balance of inflammatory cytokines

Nephrology Dialysis Transplantation, 2007

Background. Elevated plasma levels of cytokines have been associated with an increased risk of co... more Background. Elevated plasma levels of cytokines have been associated with an increased risk of congestive heart failure (CHF) even in people without history of myocardial infarction. Here we have tested the hypothesis that effective removal of pro-inflammatory cytokines in patients with advanced CHF unresponsive to diuretic treatment is associated with diuresis restoration and with a significant reduction of B-type natriuretic peptide (BNP) circulating levels. Methods. We prospectively enrolled 10 patients with decompensated CHF (NYHA classes III-IV). Five patients unresponsive to diuretic treatment underwent a short course of intermittent haemodiafiltration (iHDF), whereas five patients responsive to diuretics were treated with intravenous boluses of furosemide. Renal function was similar between the two groups. Results. Excess body fluids were removed in both groups always resulting in a reduction of pulmonary congestion and peripheral oedema. NYHA class improved in all patients, but one treated by intravenous boluses of furosemide. Only patients treated with iHDF showed a significant reduction of circulating interleukin-8 and monocyte chemoattractant protein-1. After the end of iHDF treatment, patients showed consistent restoration of diuretic responsiveness to significantly lower doses of oral furosemide up to one month of follow-up. Plasma levels of BNP before treatment were significantly higher in the iHDF group, lowering significantly in both groups after treatment. Conclusions. Our results suggest that HDF is an effective treatment for patients with advanced CHF when cytokines have to be cleared and diuretic responsiveness needs to be restored. In our experience, iHDF is a cost-effective option when compared with continuous ultrafiltration methods because it can be performed in a routine dialysis unit without adjunctive costs for machinery or personnel training.

Research paper thumbnail of Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure

Journal of the American College of Cardiology, 2001

We sought a better understanding of the coupling between right ventricular ejection fraction (RVE... more We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS During a median follow-up period of 17 Ϯ 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r ϭ 0.66, p Ͻ 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p Ͻ 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.

Research paper thumbnail of Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

Journal of the American College of Cardiology, 2008

The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. Back... more 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 Ն10 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.

Research paper thumbnail of Clinical significance of exercise-induced silent myocardial ischemia in patients with coronary artery disease

Journal of the American College of Cardiology, 1987

Research paper thumbnail of Restrictive Cardiomyopathy, Atrioventricular Block and Mild to Subclinical Myopathy in Patients With Desmin-Immunoreactive Material Deposits

Journal of the American College of Cardiology, 1998

Objectives. We present clinical data and heart and skeletal muscle biopsy findings from a series ... more Objectives. We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. Background. Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. Methods. Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. Results. Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin-one of normal and another of lower molecular weight-in cardiac and skeletal muscle of the familial cases. Conclusions. Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin.

Research paper thumbnail of Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease

Journal of the American College of Cardiology, 2002

We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated ... more We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated cardiomyopathies (DCM) associated with atrioventricular block (AVB) or increased serum creatine-phosphokinase (sCPK), and the corresponding changes in myocardial and protein expression. BACKGROUND It has been reported that familial DCM, associated with conduction disturbances or variable myopathies, is causally linked to LMNA gene defects. METHODS The LMNA gene and myocardial ultrastructural and immunochemical changes were analyzed in 73 cases of DCM (49 pure, 15 with AVB [seven familial, eight sporadic], 9 with increased sCPK), four cases of familial AVB and 19 non-DCM heart diseases. The normal controls included eight heart donor biopsies for tissue studies and 107 subjects for LMNA gene studies. RESULTS Five novel LMNA mutations (K97E, E111X, R190W, E317K, four base pair insertion at 1,713 cDNA) were identified in five cases of familial autosomal dominant DCM with AVB (5/15: 33%). The LMNA expression of the myocyte nuclei was reduced or absent. Western blot protein analyses of three hearts with different mutations showed an additional 30-kDa band, suggesting a degrading effect of mutated on wild-type protein. Focal disruptions, bleb formation and nuclear pore clustering were documented by electron microscopy of the myocyte nuclear membranes. None of these changes and no mutations were found in the nine patients with DCM and increased sCPK or in the disease and normal controls. CONCLUSIONS The LMNA gene mutations account for 33% of the DCMs with AVB, all familial autosomal dominant. Increased sCPK in patients with DCM without AVB is not a useful predictor of LMNA mutation.

Research paper thumbnail of Long-term carvedilol treatment in idiopathic dilated cardiomyopathy: biological effects beyond pharmacological activity

Journal of the American College of Cardiology, 2002

Major Depressive Disorder (MDD) is a common entity in patients with cardiovascular (CAD) disease.... more Major Depressive Disorder (MDD) is a common entity in patients with cardiovascular (CAD) disease. Studies have previously demonstrated that MDD is present in 20%-45%

Research paper thumbnail of Optimal Pharmacologic and Non-pharmacologic Management of Cardiac Transplant Candidates: Approaches to Be Considered Prior to Transplant Evaluation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates—2006

The Journal of Heart and Lung Transplantation, 2006

10 mg qd Candesartan ARB 4-8 mg qd 32 mg qd Losartan ARB 12.5 mg qd 50 mg qd Valsartan ARB 20 mg ... more 10 mg qd Candesartan ARB 4-8 mg qd 32 mg qd Losartan ARB 12.5 mg qd 50 mg qd Valsartan ARB 20 mg bid 160 mg bid Eplerenone Selective aldosterone receptor blocker 25 mg qd 50 mg qd Spironolactone Aldosterone receptor blocker 12.5-25 mg qd 25-50 mg qd ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; bid, twice daily; d, day; qd, once daily; tid, three times daily. 1004 Jessup et al.

Research paper thumbnail of Haemodynamic effects of glyceryl trinitrate during continuous 24 hour infusion in patients with heart failure

Heart, 1994

Objective-To investigate whether the susceptibility to tolerance to glyceryl trinitrate is simila... more Objective-To investigate whether the susceptibility to tolerance to glyceryl trinitrate is similar in different vascular beds in patients with chronic heart failure.

Research paper thumbnail of Importance of the echocardiographic evaluation of right ventricular function in patients with AL amyloidosis

European Journal of Heart Failure, 2007

Patients with AL amyloidosis often present with signs of congestive heart failure. This study was... more Patients with AL amyloidosis often present with signs of congestive heart failure. This study was prospectively designed to assess the significance of RV dysfunction in AL amyloidosis. Seventy-four patients with biopsy proven AL amyloidosis underwent a thorough echocardiographic evaluation. A tricuspid annular plane systolic excursion (TAPSE)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;17 mm was taken as marker of RV dysfunction. Plasma NT-proBNP determinations were performed in all cases. RV function was normal in 60 patients and reduced in 14 patients. Patients with RV dysfunction had thicker left ventricular (LV) walls (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), lower LV end-diastolic volumes (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), lower LV ejection fraction (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) and more frequently a restrictive LV filling pattern (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). RV dimensions and RV free wall thickness were not significantly different in the two groups. A thick interventricular septum and a reduced TAPSE were associated with high NT-proBNP levels (both p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Seven patients died during a median follow-up period of 19 months; TAPSE&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;17 mm was the only echocardiographic parameter associated with poor survival. In patients with AL amyloidosis, RV dysfunction is associated with more severe involvement of the left ventricle, higher plasma levels of NT-proBNP and with poor prognosis.

Research paper thumbnail of Rescreening of ?healthy? relatives of patients with dilated cardiomyopathy identifies subgroups at risk of developing the disease

European Heart Journal Supplements, 2004

Objectives To test the diagnostic impact of the non-invasive rescreening of relatives of index pa... more Objectives To test the diagnostic impact of the non-invasive rescreening of relatives of index patients consecutively diagnosed as having dilated cardiomyopathy. Background The aim of rescreening asymptomatic healthy relatives of DCM patients is to diagnose newly affected subjects and evaluate the predictive significance of the instrumental abnormalities found at the first screening. Methods and results Two hundred and three healthy relatives of 73 consecutive index patients with DCM (18 with familial disease at first screening) underwent rescreening involving a clinical examination, electro-and echocardiography, and biochemical tests a median of 29.3 months after the first screening. Seven relatives had developed the diagnostic criteria for DCM during the screeningrescreening interval. Of the 24 healthy relatives with left ventricular end-diastolic diameter enlargement and normal function at the first screening, nine had normalised, seven showed persistent enlargement, three had worsened, and five had developed the disease criteria at rescreening. Of the three relatives with atrioventricular block at the first screening, one had developed DCM. Finally, one of the relatives with normal echocardiographic and electrocardiographic results at the first screening, had developed the disease. Three of the newly diagnosed subjects came from families with evidence-based familial DCM, and four from families with what was defined as sporadic DCM at the first screening. Conclusions Medium-term rescreening of the relatives of DCM patients can identify a significant number of newly affected patients (3.5%).

Research paper thumbnail of Cardiomyology: an attempt to link structural cardiac and skeletal muscle damage in patients with dilated cardiomyopathy

European Heart Journal Supplements, 2004

Background Patients with chronic heart failure syndrome may develop a myopathy contributing to mu... more Background Patients with chronic heart failure syndrome may develop a myopathy contributing to muscle wasting and exercise intolerance. Little is known about skeletal muscle pathology in patients with dilated cardiomyopathy (DCM). Aims To correlate skeletal muscle biopsy (SMB) findings with endomyocardial biopsy (EMB) and clinical/functional data in DCM patients. Methods and results SMBs and EMBs were morphometrically and morphologically analysed in 30 consecutive patients aged 40.7 ± 14 years (16-63), including 25 in NYHA classes I and II. Four had familial DCM. Serum creatine-phosphokinase (sCPK) was normal in 23 and slightly increased in seven. All the SMBs showed morphological (including non-recurrent changes different from those in the EMBs) and morphometric changes, with atrophic fibres in all cases (atrophy factor >150 in six NYHA II patients) and necrotic fibres in three. The SMBs of two patients with EMB-proven myocarditis showed inflammation. Plotting the morphometric factors against age at symptom onset, age at diagnosis, follow-up, clinical outcome, ejection fraction and sCPK levels showed that only sCPK >180 mU/ml correlated with atrophy factor. Conclusions The use of SMB in DCM patients documents some aspecific subclinical muscle damage that is unrelated to the functional class and duration of the DCM. However, this information does not contribute to identify the aetiology or managing the disease.

Research paper thumbnail of Clinically Significant Drug Interactions with Cyclosporin

Clinical Pharmacokinetics, 1996

Research paper thumbnail of In-hospital Heart Rate Reduction With Beta Blockers and Ivabradine Early After Recovery in Patients With Acute Decompensated Heart Failure Reduces Short-Term Mortality and Rehospitalization

Frontiers in Cardiovascular Medicine, 2021

Objective: In the past years, heart rate (HR) has emerged as a highly relevant modifiable risk fa... more Objective: In the past years, heart rate (HR) has emerged as a highly relevant modifiable risk factor for heart failure (HF) patients. However, most of the clinical trials so far evaluated the role of HR in stable chronic HF cohorts. The aim of this multi-center, prospective observational study was to assess the association between HR and therapy with HR modulators (beta blockers, ivabradine, or a combination of ivabradine and beta blockers) at hospital discharge with patients' cardiovascular mortality and re-hospitalization at 6 months in acutely decompensated HF patients.Materials and Methods: We recruited 289 HF patients discharged alive after admission for HF decompensation from 10 centers in northern Italy over 9 months (from April 2017 to January 2018). The primary endpoint was the combination of cardiovascular mortality or re-hospitalizations for HF at 6 months.Results: At 6 months after discharge, 64 patients were readmitted (32%), and 39 patients died (16%). Multivariat...

Research paper thumbnail of Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry

Circulation, Jan 15, 2018

Background-There is controversy regarding outcome of patients with acute myocarditis (AM), and la... more Background-There is controversy regarding outcome of patients with acute myocarditis (AM), and lack of data 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 multi-center 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 and those older than 50 years without coronary angiography were excluded. The final study population comprised 443 patients (median age 34 years, 19.4% female) with AM diagnosed either by endomyocardial biopsy (EMB) or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance (CMR). Results-At presentation, 118 patients (26.6%) had either left ventricular (LV) ejection fraction (EF) <50%, sustained ventricular arrhythmias (VA) or a low cardiac output syndrome (LCOS) whilst 325 (73.4%) had no such complications. EMB was performed in 56/443 (12.6%), and a baseline CMR was performed in 415/443 (93.7%) of patients. Cardiac mortality plus heart transplant (HTx) at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus HTx 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 (post-discharge death and HTx, sustained VA treated with electrical shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at 5-year follow up, with a higher incidence in patients with complicated forms (10.8% vs. 0% in uncomplicated AM, Log-rank p<0.0001). Beta adrenoceptor blockers were the most frequently employed 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 CMR and 8/55 (14.5%) with complications at presentation had LVEF<50% compared with 1/145 (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 LVEF<50%, VA or LCOS at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent LV systolic dysfunction.

Research paper thumbnail of Pulmonary hypertension: classification and diagnostic algorithm

Italian heart journal : official journal of the Italian Federation of Cardiology, 2005

Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progre... more Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and premature death. Recently, the diagnostic approach has been more clearly defined according to the new clinical classification and with consensus reached on algorithms of various investigative tests and procedures that exclude other causes and ensure an accurate diagnosis of PAH. The diagnostic procedures include clinical history and physical examination, ECG, chest X-ray, transthoracic Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, ventilation and perfusion lung scan, high-resolution computed tomography of the lungs, contrast-enhanced spiral computed tomography of the lungs and pulmonary angiography, blood tests and immunology, abdominal ultrasound scan, exercise capacity assessment, and hemodynamic evaluation. Invasive and non-invasive markers of disease severity, e...

Research paper thumbnail of Infusion therapy in severe heart failure. A reappraisal

Italian heart journal : official journal of the Italian Federation of Cardiology, 2003

Decompensated heart failure is associated with high rates of morbidity and mortality and it is re... more Decompensated heart failure is associated with high rates of morbidity and mortality and it is responsible for numerous hospitalizations. The current approach to acute exacerbations is based on diuretics, vasodilators and inotropes. Compared with the impressive development of new therapeutic agents designed for other cardiovascular diseases, little progress has been observed in developing new drugs for the treatment of decompensated heart failure. Moreover, a series of controlled clinical trials failed to show a better outcome or a reduction in morbidity during treatment with inotropes, even though promising results were recently observed in controlled clinical trials with new classes of drugs, such as calcium sensitizers and nesiritide; these agents will probably modify the treatment options of decompensated heart failure in the coming years.

Research paper thumbnail of Coexistence of mitochondrial DNA and beta  myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure

Heart, 1998

Objective-To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patie... more Objective-To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with myosin heavy chain (MHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. Design-Molecular analysis of MHC and mtDNA gene defects in patients with HCM. Setting-Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy. Patients-Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional aVected patients and 27 unaVected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included an additional 27 patients with HCM and 102 with dilated cardiomyopathy. Intervention-Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens. Main outcome measures-Screening for mutations in MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing. Results-One proband (kindred A) (plus seven aVected relatives) had arginine 249 glutamine (Arg249Gln) MHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel MHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and B) were identical, but diVerent from those of the two patients with Lys450Glu plus T9957C(Phe->Leu) mutations (kindred C). Cytochrome C oxidase activity and histoenzymatic staining were severely decreased in the two patients in kindreds A and B, but were unaVected in the two in kindred C. Conclusions-MHC gene and mtDNA mutations may coexist in patients with HCM and end stage congestive heart failure. Although MHC gene mutations seem to be the true determinants of HCM, both mtDNA mutations in these patients have known prerequisites for pathogenicity. Coexistence of other genetic abnormalities in MHC linked HCM, such as mtDNA mutations, may contribute to variable phenotypic expression and explain the heterogeneous behaviour of HCM.

Research paper thumbnail of Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy

Cardiovascular ultrasound, Jan 25, 2003

It has been suggested that an extensive contractile reserve identified recognised by means of dob... more It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. We studied 26 patients (21 males and five females) with a mean age of 58 PlusMinus; 10 years: 11 were not receiving beta-blockers...

Research paper thumbnail of Design of the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study to assess the ability of remote monitoring to treat and triage patients more effectively

Trials, 2009

Background: Heart failure patients with implantable defibrillators (ICD) frequently visit the cli... more Background: Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier. Methods: The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink ® monitor for remote transmission or the conventional method of inperson evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations.

Research paper thumbnail of Intermittent haemodiafiltration in refractory congestive heart failure: BNP and balance of inflammatory cytokines

Nephrology Dialysis Transplantation, 2007

Background. Elevated plasma levels of cytokines have been associated with an increased risk of co... more Background. Elevated plasma levels of cytokines have been associated with an increased risk of congestive heart failure (CHF) even in people without history of myocardial infarction. Here we have tested the hypothesis that effective removal of pro-inflammatory cytokines in patients with advanced CHF unresponsive to diuretic treatment is associated with diuresis restoration and with a significant reduction of B-type natriuretic peptide (BNP) circulating levels. Methods. We prospectively enrolled 10 patients with decompensated CHF (NYHA classes III-IV). Five patients unresponsive to diuretic treatment underwent a short course of intermittent haemodiafiltration (iHDF), whereas five patients responsive to diuretics were treated with intravenous boluses of furosemide. Renal function was similar between the two groups. Results. Excess body fluids were removed in both groups always resulting in a reduction of pulmonary congestion and peripheral oedema. NYHA class improved in all patients, but one treated by intravenous boluses of furosemide. Only patients treated with iHDF showed a significant reduction of circulating interleukin-8 and monocyte chemoattractant protein-1. After the end of iHDF treatment, patients showed consistent restoration of diuretic responsiveness to significantly lower doses of oral furosemide up to one month of follow-up. Plasma levels of BNP before treatment were significantly higher in the iHDF group, lowering significantly in both groups after treatment. Conclusions. Our results suggest that HDF is an effective treatment for patients with advanced CHF when cytokines have to be cleared and diuretic responsiveness needs to be restored. In our experience, iHDF is a cost-effective option when compared with continuous ultrafiltration methods because it can be performed in a routine dialysis unit without adjunctive costs for machinery or personnel training.

Research paper thumbnail of Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure

Journal of the American College of Cardiology, 2001

We sought a better understanding of the coupling between right ventricular ejection fraction (RVE... more We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS During a median follow-up period of 17 Ϯ 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r ϭ 0.66, p Ͻ 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p Ͻ 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.

Research paper thumbnail of Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

Journal of the American College of Cardiology, 2008

The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. Back... more 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 Ն10 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.

Research paper thumbnail of Clinical significance of exercise-induced silent myocardial ischemia in patients with coronary artery disease

Journal of the American College of Cardiology, 1987

Research paper thumbnail of Restrictive Cardiomyopathy, Atrioventricular Block and Mild to Subclinical Myopathy in Patients With Desmin-Immunoreactive Material Deposits

Journal of the American College of Cardiology, 1998

Objectives. We present clinical data and heart and skeletal muscle biopsy findings from a series ... more Objectives. We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. Background. Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. Methods. Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. Results. Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin-one of normal and another of lower molecular weight-in cardiac and skeletal muscle of the familial cases. Conclusions. Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin.

Research paper thumbnail of Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease

Journal of the American College of Cardiology, 2002

We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated ... more We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated cardiomyopathies (DCM) associated with atrioventricular block (AVB) or increased serum creatine-phosphokinase (sCPK), and the corresponding changes in myocardial and protein expression. BACKGROUND It has been reported that familial DCM, associated with conduction disturbances or variable myopathies, is causally linked to LMNA gene defects. METHODS The LMNA gene and myocardial ultrastructural and immunochemical changes were analyzed in 73 cases of DCM (49 pure, 15 with AVB [seven familial, eight sporadic], 9 with increased sCPK), four cases of familial AVB and 19 non-DCM heart diseases. The normal controls included eight heart donor biopsies for tissue studies and 107 subjects for LMNA gene studies. RESULTS Five novel LMNA mutations (K97E, E111X, R190W, E317K, four base pair insertion at 1,713 cDNA) were identified in five cases of familial autosomal dominant DCM with AVB (5/15: 33%). The LMNA expression of the myocyte nuclei was reduced or absent. Western blot protein analyses of three hearts with different mutations showed an additional 30-kDa band, suggesting a degrading effect of mutated on wild-type protein. Focal disruptions, bleb formation and nuclear pore clustering were documented by electron microscopy of the myocyte nuclear membranes. None of these changes and no mutations were found in the nine patients with DCM and increased sCPK or in the disease and normal controls. CONCLUSIONS The LMNA gene mutations account for 33% of the DCMs with AVB, all familial autosomal dominant. Increased sCPK in patients with DCM without AVB is not a useful predictor of LMNA mutation.

Research paper thumbnail of Long-term carvedilol treatment in idiopathic dilated cardiomyopathy: biological effects beyond pharmacological activity

Journal of the American College of Cardiology, 2002

Major Depressive Disorder (MDD) is a common entity in patients with cardiovascular (CAD) disease.... more Major Depressive Disorder (MDD) is a common entity in patients with cardiovascular (CAD) disease. Studies have previously demonstrated that MDD is present in 20%-45%

Research paper thumbnail of Optimal Pharmacologic and Non-pharmacologic Management of Cardiac Transplant Candidates: Approaches to Be Considered Prior to Transplant Evaluation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates—2006

The Journal of Heart and Lung Transplantation, 2006

10 mg qd Candesartan ARB 4-8 mg qd 32 mg qd Losartan ARB 12.5 mg qd 50 mg qd Valsartan ARB 20 mg ... more 10 mg qd Candesartan ARB 4-8 mg qd 32 mg qd Losartan ARB 12.5 mg qd 50 mg qd Valsartan ARB 20 mg bid 160 mg bid Eplerenone Selective aldosterone receptor blocker 25 mg qd 50 mg qd Spironolactone Aldosterone receptor blocker 12.5-25 mg qd 25-50 mg qd ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; bid, twice daily; d, day; qd, once daily; tid, three times daily. 1004 Jessup et al.

Research paper thumbnail of Haemodynamic effects of glyceryl trinitrate during continuous 24 hour infusion in patients with heart failure

Heart, 1994

Objective-To investigate whether the susceptibility to tolerance to glyceryl trinitrate is simila... more Objective-To investigate whether the susceptibility to tolerance to glyceryl trinitrate is similar in different vascular beds in patients with chronic heart failure.

Research paper thumbnail of Importance of the echocardiographic evaluation of right ventricular function in patients with AL amyloidosis

European Journal of Heart Failure, 2007

Patients with AL amyloidosis often present with signs of congestive heart failure. This study was... more Patients with AL amyloidosis often present with signs of congestive heart failure. This study was prospectively designed to assess the significance of RV dysfunction in AL amyloidosis. Seventy-four patients with biopsy proven AL amyloidosis underwent a thorough echocardiographic evaluation. A tricuspid annular plane systolic excursion (TAPSE)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;17 mm was taken as marker of RV dysfunction. Plasma NT-proBNP determinations were performed in all cases. RV function was normal in 60 patients and reduced in 14 patients. Patients with RV dysfunction had thicker left ventricular (LV) walls (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), lower LV end-diastolic volumes (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), lower LV ejection fraction (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) and more frequently a restrictive LV filling pattern (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). RV dimensions and RV free wall thickness were not significantly different in the two groups. A thick interventricular septum and a reduced TAPSE were associated with high NT-proBNP levels (both p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Seven patients died during a median follow-up period of 19 months; TAPSE&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;17 mm was the only echocardiographic parameter associated with poor survival. In patients with AL amyloidosis, RV dysfunction is associated with more severe involvement of the left ventricle, higher plasma levels of NT-proBNP and with poor prognosis.

Research paper thumbnail of Rescreening of ?healthy? relatives of patients with dilated cardiomyopathy identifies subgroups at risk of developing the disease

European Heart Journal Supplements, 2004

Objectives To test the diagnostic impact of the non-invasive rescreening of relatives of index pa... more Objectives To test the diagnostic impact of the non-invasive rescreening of relatives of index patients consecutively diagnosed as having dilated cardiomyopathy. Background The aim of rescreening asymptomatic healthy relatives of DCM patients is to diagnose newly affected subjects and evaluate the predictive significance of the instrumental abnormalities found at the first screening. Methods and results Two hundred and three healthy relatives of 73 consecutive index patients with DCM (18 with familial disease at first screening) underwent rescreening involving a clinical examination, electro-and echocardiography, and biochemical tests a median of 29.3 months after the first screening. Seven relatives had developed the diagnostic criteria for DCM during the screeningrescreening interval. Of the 24 healthy relatives with left ventricular end-diastolic diameter enlargement and normal function at the first screening, nine had normalised, seven showed persistent enlargement, three had worsened, and five had developed the disease criteria at rescreening. Of the three relatives with atrioventricular block at the first screening, one had developed DCM. Finally, one of the relatives with normal echocardiographic and electrocardiographic results at the first screening, had developed the disease. Three of the newly diagnosed subjects came from families with evidence-based familial DCM, and four from families with what was defined as sporadic DCM at the first screening. Conclusions Medium-term rescreening of the relatives of DCM patients can identify a significant number of newly affected patients (3.5%).

Research paper thumbnail of Cardiomyology: an attempt to link structural cardiac and skeletal muscle damage in patients with dilated cardiomyopathy

European Heart Journal Supplements, 2004

Background Patients with chronic heart failure syndrome may develop a myopathy contributing to mu... more Background Patients with chronic heart failure syndrome may develop a myopathy contributing to muscle wasting and exercise intolerance. Little is known about skeletal muscle pathology in patients with dilated cardiomyopathy (DCM). Aims To correlate skeletal muscle biopsy (SMB) findings with endomyocardial biopsy (EMB) and clinical/functional data in DCM patients. Methods and results SMBs and EMBs were morphometrically and morphologically analysed in 30 consecutive patients aged 40.7 ± 14 years (16-63), including 25 in NYHA classes I and II. Four had familial DCM. Serum creatine-phosphokinase (sCPK) was normal in 23 and slightly increased in seven. All the SMBs showed morphological (including non-recurrent changes different from those in the EMBs) and morphometric changes, with atrophic fibres in all cases (atrophy factor >150 in six NYHA II patients) and necrotic fibres in three. The SMBs of two patients with EMB-proven myocarditis showed inflammation. Plotting the morphometric factors against age at symptom onset, age at diagnosis, follow-up, clinical outcome, ejection fraction and sCPK levels showed that only sCPK >180 mU/ml correlated with atrophy factor. Conclusions The use of SMB in DCM patients documents some aspecific subclinical muscle damage that is unrelated to the functional class and duration of the DCM. However, this information does not contribute to identify the aetiology or managing the disease.