Gabriele Castelli

University of Florence, Florens, Tuscany, Italy

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Publications (31)90.29 Total impact

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    ABSTRACT: Genes associated with hypertrophic cardiomyopathy (HC) are not uniformly expressed in the atrial myocardium. Whether this may impact susceptibility to atrial fibrillation (AF) is unresolved. To analyze the prevalence and clinical correlates of AF in relation to genotype in a large HC cohort. Prevalence and clinical profile of AF were assessed in 237 HC patients, followed for 14±10 years. Patients were divided into three genetic subgroups: a) MYBPC3 (58%), b) MYH7 (28%) and c) other genotypes (14%; comprising TNNT2, TNNI3, TPM1, MYL2, complex genotypes, Z-line and EC coupling genes).Left atrial size was similar in the three subsets. AF occurred in 74 HC patients (31%), with no difference among groups (31% in MYBPC3, 37 % in MYH7and 18% in other genotypes, p=0.15), paroxysmal/persistent AF (12%, 18% and 12%, respectively; p=0.53), paroxysmal/persistent evolved to permanent (12%, 12% and 3%, p=0.36) or permanent AF (7%, 7% and 3%, p=0.82). Age at AF onset was younger in the group with other genotypes (37±10 years) compared to the first two groups (53±14 and 51±17, respectively; p=0.05), due to early onset associated with complex genotypes and a specific JPH2 mutation associated with abnormal intracellular calcium handling. At multivariate analysis, independent predictors of AF were atrial diameter (p=<0.05) and age at diagnosis (p=0.09), but not genetic subtype (p=0.35). In conclusion, in HC patients, genetic testing cannot be used in clinical decision-making with regard to management strategies for AF. Genotype is not predictive of onset or severity of AF, which appears rather driven by hemodynamic determinants of atrial dilatation. Exceptions are represented by rare genes suggesting specific molecular pathways for AF in genetic cardiomyopathies.
    No preview · Article · Jan 2016
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    ABSTRACT: Background: -The clinical course of patients with hypertrophic cardiomyopathy (HCM) and advanced heart failure (HF) subtended by progressive left ventricular (LV) dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator (ICD) and heart transplantation (HT) in HCM patients evaluated at two Italian referral centers over 3 decades. Methods and results: -All-cause mortality and a combined end-point including death, HT or appropriate ICD shock was assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire HCM cohort) followed for 6.1±6.9 years after development of NYHA class III-IV symptoms. At enrollment, LV ejection fraction was <50% in 55 patients and >50% in 16; all had restrictive LV filling. During follow-up, 35 patients died (49%%; 5-year rate 49%) and 53 met the combined end-point (75%; 5-year rate 62%). Most events occurred in the three years after HF onset (17%/year, compared to only 3%/year subsequently). Appropriate ICD shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed and 13 excluded; two early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. Conclusions: -In HCM, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first three years following onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favourable but requires early consideration, as the window of opportunity may be short.
    No preview · Article · Oct 2015 · Circulation Heart Failure
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    ABSTRACT: Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi. In endemic areas (South and Central America), Chagas disease represents a relevant public health issue, and is the most frequent cause of cardiomyopathy. In nonendemic areas, such as Europe, Chagas disease represents an emerging problem following the establishment of sizeable communities from Brazil and Bolivia. Chagas cardiomyopathy represents the most frequent and serious complication of chronic Chagas disease, affecting about 20-30% of patients, potentially leading to heart failure, arrhythmias, thromboembolism, stroke and sudden death. Because late complications of Chagas disease may develop several years or even decades after the acute infection, it may be extremely challenging to reach the correct diagnosis in patients long removed from the countries of origin. We report two examples of Chagas cardiomyopathy in South American women permanently residing in Italy for more than 20 years, presenting with cardiac manifestations ranging from left ventricular dysfunction and heart failure to isolated ventricular arrhythmias. The present review emphasizes that Chagas disease should be considered as a potential diagnosis in patients from endemic areas presenting with 'idiopathic' cardiac manifestations, even when long removed from their country of origin, with potential implications for treatment and control of Chagas disease transmission.
    No preview · Article · Jul 2014 · Journal of Cardiovascular Medicine

  • No preview · Article · Aug 2013 · International journal of cardiology
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    ABSTRACT: Background: Chemotherapy-induced cardiomyopathy (CI-CM) is the most frequent complication of cytotoxic drugs cardiotoxicity and portends a poor prognosis: old studies on small populations, mainly treated with digoxin and diuretics, reported a 2-year mortality rate of about 60%. Recent data, however, show a fundamental role of an early treatment with the modern heart failure (HF) therapy as a determinant of recovery from CI-CM. Aim: To demonstrate the actual improving in survival of a cohort of CI-CM pts followed at our Center in the last two decades. Methods: From 1990 to 2012 we enrolled 62 consecutive pts (32,3% M, age 49±14 y) with CI-CM. Follow up was 70±62 months. At baseline mean left ventricular (LV) ejection fraction (EF) was 39.5±10%, LV end diastolic diameter index 32.1±5 mm/m2, NYHA class 2.6±1.2. Hypertension was present in 15%, diabetes in 7% and hypercholesterolemia in 10% of pts; 10% were smokers; 64% received chemotherapy due to non-Hodgkin's lymphoma, 12% for Hodgkin's disease, 10% for breast cancer while a minority of pts were treated because of leukemia, osteosarcoma, hepatocellular carcinoma and glioblastoma; 23% had a history of previous antineoplastic treatment for the same or other types of cancer; 41% received mediastinum radiotherapy (RT); 63% showed symptoms of HF. Two or more antineoplastic treatment/RT-related complications, beyond LV dilatation/dysfunction, were evident in 21% of pts. Mean time from last antineoplastic treatment dose and CI-CM diagnosis was 39±64 months. A late-onset cardiotoxicity was reported in the majority of pts with LV dilatation/dysfunction occurring even after 23 years. At the end of follow up 64,5% of pts were receiving ACE-inhibitors, 18% ARBs and 90% betablockers (BB): the mean dose was 67%, 75% and 39% of the HF guidelines recommended dosage, respectively. Mineral corticoid receptor antagonists (MRA) were administered in 45% of pts; 76% received ACEI/ARBs plus BB and 42% of them were also on MRA. Results: The combined end-point of all cause death/heart transplantation was reached in 25 pts (40,3%): 23.8% of deaths were due to refractory HF, 14.3% were non cardiac/cancer-related and 61.9% non cardiac/possibly cancer-related. Overall survival was 72,6% at 5 years, 47,7% at 10 years. Conclusions: Our data show an improvement in survival of CI-CM pts with respect to data available in current literature. This finding presumably reflects the impact of evidence-based treatment of HF over the years, confirming the relevance of a widespread use of such therapies in early phases of cardiotoxicity related LV dysfunction.
    Preview · Article · Aug 2013 · European Heart Journal
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    ABSTRACT: Purpose: To date, clinical studies on hypertrophic cardiomyopathy (HCM) have assessed outcome irrespective of genetic background. However, the large proportion of patients with no detectable sarcomere myofilament gene mutations, possibly including phenocopies, may confound our perception of the the natural history of HCM due to sarcomeric myofilament mutations. We therefore investigated the clinical features and outcome of 250 HCM patients followed 6±3 years after genetic identification of such mutations. The impact of the implantable cardioverter-defibrillator (ICD), both in terms of appropriate intervention rates and adverse effects, was specifically assessed. Results: Overall, 16 pts (6%; incidence 1% per year) died of cardiovascular causes, including progressive heart failure (n=7), SCD (n=5), ischemic stroke (n=1) and other non cardiac diseases (n=3). Of these, 9 (5%) occurred in the subset of patents without ICD (group 1) including 3 sudden deaths; while 7 (11%) occurred among pts with ICD (group 2), of whom 3 had prior appropriate interventions. Two of the deaths in group 2 were sudden, occurring despite the device: unfortunately, neither an autopsy nor an ICD interrogation was performed in these pts, and the exact causes of death could not be ascertained. At final evaluation, 6±3 years after genetic testing, 34 pts (14%) were in NYHA class III/IV and 25 (10%) had overt LV systolic dysfunction (LVEF <50%). Survival in the two groups was comparable (p=0.15) despite more severe clinical profile and greater prevalence of end-stage in group 2. No difference in survival was observed based on the affected gene. Among the 64 pts with ICD, only 7 (11%; 2 in primary and 5 in secondary prevention) experienced appropriate shocks for VT of VF, with an overall annual incidence of 2%. However, 16 pts (25% of the ICD subset, including 2 with appropriate shocks) experienced device-related complications such as inappropriate ICD interventions (n=10; including 4 with electric storms due to lead fracture), infections (n=4) and lead dislocation (n=6). Conclusions: In HCM patients due to sarcomere myofilament mutations, cardiovascular mortality and sudden cardiac death was low even in the presence of multiple risk factors. End-stage progression appeared to be common, supporting the hypothesis of long-term disease progression to heart failure. The ICD allowed favourable survival rates in a subset of high risk HCM patients, at the cost of considerable complication rates, even when no appropriate interventions were recorded. Sudden cardiac death may occur even after ICD implantation.
    Preview · Article · Aug 2013 · European Heart Journal
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    ABSTRACT: -Contemporary therapeutic options have led to substantial improvement in survival of heart failure (HF) patients. However, limited evidence is available specifically regarding idiopathic dilated cardiomyopathy (IDCM). We thus examined changes in prognosis of a large IDCM cohort systematically followed over the last thirty years. -From 1977 to 2011, 603 consecutive patients (age=53±12 years, 73%=male, LV ejection fraction=32±10%) fulfilling WHO criteria for IDCM, including negative coronary angiography, were followed for 8.8±6.3 years. Patients were subdivided in four enrollment periods based on HF treatment "eras": 1) 1977-1984(n=66); 2) 1985-1990(n=102); 3) 1991-2000(n=197); 4) 2001-2011(n=238). Rates of patients receiving ACEI/ARBs, beta-blockers and devices at final evaluation increased from 56%, 12%, 8% (period 1) to 97%, 86%, 17% (period 4), respectively (p<0.05). There was a trend towards enrollment of older patients with less severe LV dilatation and dysfunction over the years. During follow-up, 271 patients (45%) reached a combined end-point including death (HF-related, n=142; sudden death, n=71; non-cardiac, n=22) or cardiac transplant (n=36). A more recent enrollment period represented the most powerful independent predictor of favorable outcome [period 2 vs 1 (HR=0.64; p=0.04), period 3 vs 1 (HR=0.35; p<0.001), period 4 vs 1 (HR=0.14; p<001)]. Each period was associated with a 42% risk reduction vs the previous one (HR=0.58, 95%CI=0.50-0.67, p<0.001), reflecting marked decreases in HF-related mortality and sudden death (period 4 vs 1: HR=0.10; p<001, HR=0.13; p<0.0001, respectively). -Evidence-based treatment has led to dramatic improvement in the prognosis of IDCM over the last three decades. The benefits of controlled randomized trials can be replicated in the real world, emphasizing the importance of tailored follow-up and long-term continuity of care.
    Preview · Article · Jul 2013 · Circulation Heart Failure
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    ABSTRACT: In hypertrophic cardiomyopathy, the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) correlate with functional capacity. However, their prognostic relevance remains unresolved. We followed up 183 stable outpatients with hypertrophic cardiomyopathy (age 50 ± 17 years, 64% men) for 3.9 ± 2.8 years after NT-proBNP measurement. The primary end point included cardiovascular death, heart transplantation, resuscitated cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. The secondary end point (SE) included heart failure-related death or hospitalization, progression to end-stage disease, and stroke. The median NT-proBNP level was 615 pg/ml (intertertile range 310 to 1,025). The incidence of the primary end point in the lower, middle, and upper tertiles was 0%, 1.3%, and 2.1% annually, respectively (overall p = 0.01). On multivariate analysis, the only independent predictors of the primary end point were NT-proBNP (hazard ratio for log-transformed values 5.8, 95% confidence interval 1.07 to 31.6; p = 0.04) and a restrictive left ventricular filling pattern (hazard ratio 5.19, 95% confidence interval 1.3 to 21.9; p = 0.02). The NT-proBNP cutoff value of 810 pg/ml had the best sensitivity for the primary end point (88%), but the specificity was low (61%). The incidence of the SE in the lower, middle, and upper NT-proBNP tertiles was 4.6%, 12.0%, and 11.2% annually, respectively (overall p = 0.001). An NT-proBNP level of <310 pg/ml was associated with a 75% reduction in the rate of SE compared with a level of ≥310 pg/ml (hazard ratio 0.25, 95% confidence interval 0.11 to 0.57; p = 0.001), independent of age, left ventricular outflow tract obstruction, or atrial fibrillation. In conclusion, in stable outpatients with hypertrophic cardiomyopathy, plasma NT-proBNP proved a powerful independent predictor of death and heart failure-related events. Although the positive predictive accuracy of an elevated NT-proBNP level was modest, low values reflected true clinical stability, suggesting the possibility of avoiding or postponing aggressive treatment options.
    No preview · Article · Jul 2013 · The American journal of cardiology
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    ABSTRACT: Male patients with Anderson-Fabry disease (AFD) often exhibit cardiac involvement, characterized by LV hypertrophy (LVH), associated with severe coronary microvascular dysfunction (CMD). Whether CMD is present in patients without LVH, particularly when female, remains unresolved. The aim of the study was to investigate the presence of CMD by positron emission tomography (PET) in AFD patients of both genders, with and without evidence of LVH. We assessed myocardial blood flow following dipyridamole infusion (Dip-MBF) with (13)N-labelled ammonia by PET in 30 AFD patients (age 51 ± 13 years; 18 females) and in 24 healthy controls. LVH was defined as echocardiographic maximal LV wall thickness ≥13 mm. LVH was present in 67% of patients (n = 20; 10 males and 10 females). Dip-MBF was reduced in all patients compared with controls (1.8 ± 0.5 and 3.2 ± 0.5 mL/min/g, respectively, P < 0.001). For both genders, flow impairment was most severe in patients with LVH (1.4 ± 0.5 mL/min/g in males and 1.9 ± 0.5 mL/min/g in females), but was also evident in those without LVH (1.8 ± 0.3 mL/min/g in males and 2.1 ± 0.4 mL/min/g in females; overall P = 0.064 vs. patients with LVH). Analysis of variance (ANOVA) for the 17 LV segments showed marked regional heterogeneity of MBF in AFD (F = 4.46, P < 0.01), with prevalent hypoperfusion of the apical region. Conversely, controls showed homogeneous LV perfusion (F = 1.25, P = 0.23). Coronary microvascular function is markedly impaired in AFD patients irrespective of LVH and gender. CMD may represent the only sign of cardiac involvement in AFD patients, with potentially important implications for clinical management.
    No preview · Article · Jun 2013 · European Journal of Heart Failure
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    ABSTRACT: Heart failure and myocardial infarction result in considerable consumption of healthcare resources. Therefore, there is interest in the availability of drug therapies that can favorably modify their prognosis in the post-acute phase, reducing mortality and rehospitalization rates. Aldosterone antagonists represent a class of drugs which offer advantages in these settings, in addition to those obtained with beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, even though attention should be drawn to their potential adverse effects. In particular, eplerenone exhibits a better safety profile than spironolactone. Since it has very little affinity for glucocorticoid, androgen and progesterone receptors, eplerenone has less antiandrogenic and progestagenic effects, resulting in a lower incidence of gynecomastia. The EPHESUS study showed that eplerenone can reduce mortality in the short and long term and the rate of new hospitalizations after a myocardial infarction complicated by heart failure. In addition, in the EMPHASIS-HF study eplerenone reduced cardiovascular mortality and hospitalizations after mild heart failure (NYHA class IIa). Despite these important results, which confirmed those obtained with spironolactone in severe heart failure in the RALES study, aldosterone antagonists are still underutilized. In particular, eplerenone is not yet available in Italy, although it is recommended by the latest European Society of Cardiology guidelines.
    No preview · Article · Dec 2012 · Giornale italiano di cardiologia (2006)
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    ABSTRACT: Heart failure (HF) is one of the leading causes of hospitalization and medical expenditure, especially in elderly patients. Cooperation between specialists and general practitioners may improve outcomes. A 1-year hospital-territory disease management program was designed in collaboration with the Tuscany Region and the Ministry of Health involving specialists, general practitioners and nurses to investigate the impact of our model on healthcare organization and hospitalization rates in patients with HF. The program used a web-based clinical report form, and monitoring of patients from specialists and nurses was coordinated by the general practitioners. We enrolled 106 patients (78.3% male, mean age 74.6 years), with a mean left ventricular ejection fraction 49% and mean Charlson index 2.2. A statistically significant reduction was observed in the number of hospitalizations and emergency calls compared with the previous year. HF severity did not substantially changed in 69.8% of patients, whereas it improved in 17.0% and worsened in 13.2% (NYHA class). Our preliminary data suggest that cooperation between hospitals and medical systems in the territory by means of a web-based clinical report may result in better management of healthcare interventions in the territory with subsequent reduction of hospitalizations. An extension of this model is now ongoing for collecting data from different areas, both within and outside Tuscany.
    Full-text · Article · Sep 2012 · Giornale italiano di cardiologia (2006)
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    ABSTRACT: To evaluate the clinical, biohumoral, and haemodynamic effects of ultrafiltration vs. intravenous diuretics in patients with decompensated heart failure (HF). Signs and symptoms of volume overload are often present in these patients and standard therapy consists primarily of intravenous diuretics. Increasing evidence suggests that ultrafiltration can be an effective alternative treatment. Thirty patients with decompensated HF were randomly assigned to diuretics or ultrafiltration. Haemodynamic variables, including several novel parameters indicating the overall performance of the cardiovascular system, were continuously assessed with the Pressure Recording Analytical Method before, during, at the end of treatment (EoT) and 36 h after completing treatment. Aldosterone and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels were also measured. Patients treated with ultrafiltration had a more pronounced reduction in signs and symptoms of HF at EoT compared with baseline, and a significant decrease in plasma aldosterone (0.24 ± 0.25 vs. 0.86 ± 1.04 nmol/L; P < 0.001) and NT-proBNP levels (2823 ± 2474 vs. 5063 ± 3811 ng/L; P < 0.001) compared with the diuretic group. The ultrafiltration group showed a significant improvement (% of baseline) in a number of haemodynamic parameters, including stroke volume index (114.0 ± 11.7%; P < 0.001), cardiac index (123.0 ± 20.8%; P < 0.001), cardiac power output (114.0 ± 13.8%; P < 0.001), dP/dt(max) (129.5 ± 19.9%; P < 0.001), and cardiac cycle efficiency (0.24 ± 0.54 vs. -0.14 ± 0.50 units; P < 0.05), and a significant reduction in systemic vascular resistance 36 h after the treatment (88.0 ± 10.9%; P < 0.001), which was not observed in the diuretic group. In patients with advanced HF, ultrafiltration facilitates a greater clinical improvement compared with diuretic infusion by ameliorating haemodynamics (assessed using a minimally invasive methodology) without a marked increase in aldosterone or NT-proBNP levels.
    No preview · Article · Mar 2011 · European Journal of Heart Failure
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    ABSTRACT: The aim of this study was to investigate whether alterations in left ventricular (LV) twisting and untwisting motion could be induced by cardiac involvement in patients with immunoglobulin light-chain (AL) systemic amyloidosis. Forty-five patients with AL amyloidosis and 26 control subjects were evaluated. After standard echocardiographic measurement and two-dimensional (2D) speckle tracking echocardiography, LV rotation at both basal and apical planes, twisting, twisting rate, and longitudinal strain were measured. Tissue Doppler imaging (TDI) derived early diastolic peak velocity at septal mitral annulus (E') was also evaluated. Twenty-six of 45 patients with systemic amyloidosis were classified as having cardiac amyloidosis (CA) if the mean value of the LV wall thickness was ≥ 12 mm or not (NCA) if this value was not reached. In NCA patients, both LV twist and untwisting rate were increased while they were decreased in CA patients making them similar to the control group. Longitudinal strain was reduced only in CA patients. Impaired relaxation as indicated by E' values was progressively reduced in the course of the disease. Both twisting and untwisting motions are increased in patients with AL systemic amyloidosis with no evidence of cardiac involvement while they are reduced in patients with evident amyloidosis cardiac involvement. This finding suggests that impaired LV relaxation induces a compensatory mechanism in the early phase of the disease, which fails in more advanced stage when both twisting and untwisting rates are reduced. The increase in LV rotational mechanics could be a marker of subclinical cardiac involvement.
    No preview · Article · Oct 2010 · Echocardiography
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    ABSTRACT: Using traditional echocardiography, the diagnosis of cardiac amyloidosis (CA) is often only possible in advanced stage when recommended therapies may have adverse effects. The aim of our study was to evaluate whether additional information can be derived from Tissue and strain Doppler imaging (TDI and SDI). Forty patients with systemic amyloidosis and 24 healthy subjects underwent traditional, tissue and strain Doppler echocardiography. Patients were classified having CA if mean wall thickness (mT), was half of the sum septum and posterior wall thickness, was > or =12 mm. The following parameters were evaluated: peak early diastolic velocity (Em) as index of ventricular relaxation, mitral E-wave to Em ratio (E/Em) as index of left ventricular (LV) filling pressure and mean LV strain peak curves (mSt) as global long-axis contraction index. In non cardiac amyloidosis (NCA), both Em and mSt were lower than in age matched controls (p < 0.01, p < 0.05, respectively) and higher than in CA (p < 0.01 and p < 0.01, respectively). Both Em and mSt were related to mT (p < 0.001). A significant (p < 0.01) nonlinear relation was observed between plasma terminal of pro B-natriuretic peptide and mT, Em, E/Em and mSt. TDI and SDI are able to detect amyloid myocardial involvement in such an early stage that cannot be evidenced by using traditional echocardiography.
    No preview · Article · Jan 2009 · Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis

  • No preview · Article · Dec 2007 · Clinical Therapeutics
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    ABSTRACT: In patients with heart failure, poor ejection fraction and estimated severe aortic stenosis because of a reduced aortic valve area (AVA) and low gradients, dobutamine echocardiography (DE) was proposed to distinguish afterload mismatch from primary left ventricular dysfunction. In this setting the feasibility and safety of DE and the outcome following management based on DE results were investigated. Forty-eight patients (mean age 73 +/- 9 years; 79% males; AVA 0.7 +/- 0.2 cm2; mean aortic gradient 22 +/- 6 mmHg; ejection fraction 0.28 +/- 0.07; NYHA functional class 2.9 +/- 0.8) underwent DE and were followed up for 24 +/- 21 months. Aortic valve replacement (AVR) was offered to patients with left ventricular contractile reserve (ejection fraction increase > or = 30% at peak DE) and fixed aortic stenosis (AVA increase < or = 0.25 cm2). DE elicited a left ventricular contractile reserve in 38 patients (79%). Among these, fixed aortic stenosis was present in 28 patients, among whom 19 underwent AVR and 9 declined surgery. The 20 patients without contractile reserve or with relative stenosis (AVA increase > 0.25 cm2) were not considered eligible for surgery. During follow-up, 23 cardiovascular deaths occurred: 2/19 among operated patients, 7/9 among patients who declined surgery and 14/20 among non-eligible patients. Patients with AVR showed a significantly more favorable outcome and improved functional status as compared to the other two groups (NYHA class 1.2 +/- 0.4 vs 2.7 +/- 0.6 at baseline; p < 0.001). Conversely, non-surgical management was the strongest independent predictor of an adverse outcome (relative risk 3.6, 95% confidence interval 1.8-7.3; p < 0.0001). In patients with heart failure and estimated severe aortic stenosis, DE could identify a subgroup with a left ventricular contractile reserve and fixed aortic stenosis who gained great benefit from AVR. The clinical outcome of patients who were not operated upon was unfavorable.
    No preview · Article · Apr 2003 · Italian heart journal: official journal of the Italian Federation of Cardiology
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    ABSTRACT: Both beta-blockers as well as positive inotropic drugs may be indicated for the treatment of patients with advanced or refractory heart failure. When tolerated, beta-blocker therapy is able to counteract the adverse biologic effects produced by the chronic activation of the sympathetic nervous system and, therefore, to delay the progression of the disease. Conversely, although the long-term administration of positive inotropic agents is not recommended, these drugs may be required to face episodes of acute hemodynamic deterioration, which frequently occur in patients who are so severely impaired. Beta-blocker and positive inotropic therapies are currently viewed as alternative strategies for the management of severe heart failure patients. However, both the theoretical background and preliminary clinical evidences about the combined use of these two drug classes are suggestive of the potential for cumulative benefits and of the mutual attenuation of deleterious effects.
    No preview · Article · Sep 2002 · Italian heart journal. Supplement: official journal of the Italian Federation of Cardiology
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    ABSTRACT: Both beta-blockers as well as positive inotropic drugs may be indicated for the treatment of patients with advanced or refractory heart failure. When tolerated, beta-blocker therapy is able to counteract the adverse biologic effects produced by the chronic activation of the sympathetic nervous system and, therefore, to delay the progression of the disease. Conversely, although the long-term administration of positive inotropic agents is not recommended, these drugs may be required to face episodes of acute hemodynamic deterioration, which frequently occur in patients who are so severely impaired. Beta-blocker and positive inotropic therapies are currently viewed as alternative strategies for the management of severe heart failure patients. However, both the theoretical background and preliminary clinical evidences about the combined use of these two drug classes are suggestive of the potential for cumulative benefits and of the mutual attenuation of deleterious effects.
    No preview · Article · Aug 2002
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    ABSTRACT: The most frequent localization of amyloid in transthyretin (TTR) mutations is in the peripheral nerve, causing familial amyloidpolyneuropathy (FAP). It is generally accompanied by involvement of other organs such as the myocardium and kidney. To date, over 70 TTR point mutations have been reported in literature, with different phenotypes depending on the location of the mutation in the TTR gene. This paper deals with a point mutation in exon 2 position 47 of the TTR gene, encoding the substitution of glycine with glutamate. The mutation was found in an Italian family with 5 patients over 3 generations. The phenotype was characterised by peripheral neuropathy and autonomic dysfunction, associated in some patients with cardiomyopathy and renal involvement. The symptoms were very severe and the patients did not survive long, thus suggesting the aggressive nature of the pathological process. Moreover, in the succeeding generations of this family, there was genetic anticipation in the age of onset of the disease.
    No preview · Article · Apr 2002 · Amyloid
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    ABSTRACT: Sudden death frequently occurs in patients with idiopathic dilated cardiomyopathy. Ventricular arrhythmias are encountered in almost all cases. The prognostic significance of life-threatening arrhythmias such as successfully resuscitated ventricular fibrillation and sustained ventricular tachycardia is well known, while it is controversial for ventricular arrhythmias of a lower degree. Amiodarone has been used widely in these patients but its value in preventing sudden death is still uncertain. The aim of this study was to evaluate the prognostic significance of runs of nonsustained ventricular tachycardia (NSVT) as a hallmark for sudden death and the efficacy of amiodarone in preventing sudden death and reducing overall mortality in a large series of patients with dilated cardiomyopathy. Over the period between 1983 and 1994, a series of 151 consecutive patients with idiopathic dilated cardiomyopathy underwent ambulatory electrocardiographic monitoring for a mean period of 191 hours/patient. Seventy-nine patients (56 male, mean age 50.7 +/- 13.1 years) (group A) had ventricular arrhythmias of Lown class < or = 4A, while 72 (53 male, mean age 48.6 +/- 12.8 years) (group B) had one or more NSVT runs. The two groups were well matched in terms of clinical features. Mean follow-up period was 86.8 +/- 38.7 and 74.7 +/- 39.5 months, respectively. In group A no antiarrhythmic drug was administered, while in group B 54/72 patients were treated with amiodarone (mean dosage 300 mg/day) for a mean period of 69.7 +/- 37.8 months (group B1). The remaining 18 patients received class I antiarrhythmic drugs, mexiletine (12) and propaphenone (6) for a mean period of 46.1 +/- 29.4 months, because amiodarone was contraindicated (3) or serious side-effects occurred during amiodarone treatment (15), which was discontinued after a mean period of 3.8 +/- 3.1 months (group B2). The cumulative survival probability in the whole population was 86.6% at two years and 65.6% at five years. The rate of sudden death was 6.0% at two years and 18.3% at five years. No statistically significant difference was observed in terms of all-cause mortality or sudden death in the three groups (A, B1, B2). In group B1, amiodarone determined the disappearance of NSVT at Holter monitoring in 50% of patients (27), with no significant difference in the rate of sudden death between the two subgroups. In unselected patients with idiopathic dilated cardiomyopathy, cardiovascular mortality does not differ between those with NSVT on chronic amiodarone treatment and those without NSVT who have not undergone antiarrhythmic therapy. There was a trend towards a higher overall and sudden mortality rate in patients with NSVT treated with other antiarrhythmic drugs vs patients with NSVT treated with amiodarone, but due to the small size of the first group no significant difference could be calculated. Assuming NSVT as a potential prognostic marker for sudden death, amiodarone treatment may have exerted a beneficial effect in these patients, but this statement is only a presumption due to the limitations of our study. The disappearance of NSVT during amiodarone treatment is not predictive of a reduced rate in sudden death, so that the potential effect of the drug does not appear to be related to the suppression of NSVT at Holter monitoring.
    No preview · Article · May 1999 · Giornale italiano di cardiologia

Publication Stats

328 Citations
90.29 Total Impact Points

Institutions

  • 1996-2015
    • University of Florence
      • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      Florens, Tuscany, Italy
  • 2009-2013
    • Azienda Ospedaliero Universitaria Careggi
      Florens, Tuscany, Italy