Franco Cecchi

University of Florence, Florens, Tuscany, Italy

Are you Franco Cecchi?

Claim your profile

Publications (182)1010.19 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Post-Stroke Pain (PSP) is a common and disabling complication, difficult to treat, that often decreases patients' quality of life (QoL). The hypothesis is that PSP may negatively affect rehabilitation treatment. To quantify and characterize pain in a sample of post---stroke patients undergoing rehabilitation and to investigate the impact of pain in slowing down or discontinuing the rehabilitation program. Multicenter cross--sectional study. Inpatients and outpatients of rehabilitation department. One hundred and six subacute and chronic stroke patients. Pain intensity was measured with the NRS or the PAINAD (if cognitive/language impairment was present); pain characteristics were assessed with the DN4, and NPSI questionnaire. Qol was measured with the SF--36. A clinical assessment and a semi-structured questionnaire on pain occurrence, impact, and management was administered by the physiotherapist in charge of the patients and by the physician. About 1/3 of the patients (32.9%) with normal cognitive/language reported pain occurrence after stroke; 81.8% of them had NRS ≥3 and 31.8% DN4≥4 (meaning neuropathic origin of pain). In about 20% of the patients the PAINAD was used to measure pain; 17.4% of them presented a score ≥3. In 24.5% of our sample, pain influenced rehabilitation treatment. In 16% of the whole sample, pain influenced patients' attention during rehabilitation session. Patients with hypoesthesia presented significantly higher neuropathic pain scores than patients with normal sensory function. Regarding QoL, we found that patients with higher neuropathic pain showed more severe deterioration of mental aspects of QoL, where patients with higher nociceptive pain presented more severe deterioration of physical aspects of QoL. The results from this multicenter study showed that in about ¼ of the patients, pain negatively influenced the rehabilitation program delaying the recovery and likely increasing the cost of rehabilitation. Clinicians should pay more attention to pain, especially neuropathic pain, in post--stroke patients. Tailored pharmacological therapy, to treat and prevent pain, might improve patients' compliance during the rehabilitation process.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Contribuyente adicional: Constantinos O’Mahony (Reino Unido) Comité de la ESC para las Guías de Práctica Clínica (GPC): Jose Luis Zamorano (presidente) (España), Stephan Achenbach (Alemania), Helmut Baumgartner (Alemania), Jeroen J. Bax (Países Bajos), Héctor Bueno (España), Veronica Dean (Francia), Christi Deaton (Reino Unido), Çetin Erol (Turquía), Robert Fagard (Bélgica), Roberto Ferrari (Italia), David Hasdai (Israel), Arno W. Hoes (Países Bajos), Paulus Kirchhof (Alemania/Reino Unido), Juhani Knuuti (Finlandia), Philippe Kolh (Bélgica), Patrizio Lancellotti (Bélgica), Ales Linhart (República Checa), Petros Nihoyannopoulos (Reino Unido), Massimo F. Piepoli (Italia), Piotr Ponikowski (Polonia), Per Anton Sirnes (Noruega), Juan Luis Tamargo (España), Michal Tendera (Polonia), Adam Torbicki (Polonia), William Wijns (Bélgica) y Stephan Windecker (Suiza).
    Revista Espa de Cardiologia 01/2015; DOI:10.1016/j.recesp.2014.12.001 · 3.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. METHODS: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with >/=75% agreement and no disagreement. RESULTS: For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of >/=16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m2) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped. CONCLUSION: The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mild hypertrophy but increased arrhythmic risk characterizes the stereotypic phenotype proposed for hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations. However, whether such clinical profile is different from more prevalent thick-filament-associated disease is unresolved. This study aimed to assess clinical features and outcomes in a large cohort of patients with HCM associated with thin-filament mutations compared with thick-filament HCM. Adult HCM patients (age >18 years), 80 with thin-filament and 150 with thick-filament mutations, were followed for an average of 4.5 years. Compared with thick-filament HCM, patients with thin-filament mutations showed: 1) milder and atypically distributed left ventricular (LV) hypertrophy (maximal wall thickness 18 ± 5 mm vs. 24 ± 6 mm; p < 0.001) and less prevalent outflow tract obstruction (19% vs. 34%; p = 0.015); 2) higher rate of progression to New York Heart Association functional class III or IV (15% vs. 5%; p = 0.013); 3) higher prevalence of systolic dysfunction or restrictive LV filling at last evaluation (20% vs. 9%; p = 0.038); 4) 2.4-fold increase in prevalence of triphasic LV filling pattern (26% vs. 11%; p = 0.002); and 5) similar rates of malignant ventricular arrhythmias and sudden cardiac death (p = 0.593). In adult HCM patients, thin-filament mutations are associated with increased likelihood of advanced LV dysfunction and heart failure compared with thick-filament disease, whereas arrhythmic risk in both subsets is comparable. Triphasic LV filling is particularly common in thin-filament HCM, reflecting profound diastolic dysfunction. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 12/2014; 64(24):2589-600. DOI:10.1016/j.jacc.2014.09.059 · 15.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background-Next-generation sequencing might be particularly advantageous in genetically heterogeneous conditions, such as hypertrophic cardiomyopathy (HCM), in which a considerable proportion of patients remain undiagnosed after Sanger. In this study, we present an Italian family with atypical HCM in which a novel disease-causing variant in alpha-actinin 2 (ACTN2) was identified by next-generation sequencing. Methods and Results-A large family spanning 4 generations was examined, exhibiting an autosomal dominant cardiomyopathic trait comprising a variable spectrum of (1) midapical HCM with restrictive evolution with marked biatrial dilatation, (2) early-onset atrial fibrillation and atrioventricular block, and (3) left ventricular noncompaction. In the proband, 48 disease genes for HCM, selected on the basis of published reports, were analyzed by targeted resequencing with a customized enrichment system. After bioinformatics analysis, 4 likely pathogenic variants were identified: TTN c.21977G>A (p.Arg7326Gln); TTN c.8749A>C (p.Thr2917Pro); ACTN2 c.683T>C (p.Met228Thr); and OBSCN c.13475T>G (p.Leu4492Arg). The novel variant ACTN2 c.683T>C (p.Met228Thr), located in the actin-binding domain, proved to be the only mutation fully cosegregating with the cardiomyopathic trait in 18 additional family members (of whom 11 clinically affected). ACTN2 c.683T>C (p.Met228Thr) was absent in 570 alleles of healthy controls and in 1000 Genomes Project and was labeled as Damaging by in silico analysis using polymorphism phenotyping v2, as Deleterious by sorts intolerant from tolerant, and as Disease-Causing by Mutation Taster. Conclusions-A targeted next-generation sequencing approach allowed the identification of a novel ACTN2 variant associated with midapical HCM and juvenile onset of atrial fibrillation, emphasizing the potential of such approach in HCM diagnostic screening.
    Circulation Cardiovascular Genetics 08/2014; 7(6). DOI:10.1161/CIRCGENETICS.113.000486 · 6.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background-Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. Methods and Results-We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of >= 15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3-38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). Conclusions-Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.
    Circulation 08/2014; 130(6):484-95. DOI:10.1161/CIRCULATIONAHA.113.007094 · 14.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF) <50%. A comparison among mutated and negative ES-HC patients and a reference cohort of 181 HC patients with preserved LVEF was performed. Overall, 131 mutations (36 novel) were identified in 104 ES-HC patients (67%) predominantly affecting MYH7 and MYBPC3 (80%). Complex genotypes with double or triple mutations were present in 13% compared with 5% of the reference cohort (p = 0.013). The distribution of mutations was otherwise indistinguishable in the 2 groups. Among ES-HC patients, those presenting at first evaluation before the age of 20 had a 30% prevalence of complex genotypes compared with 19% and 21% in the subgroups aged 20 to 59 and ≥60 years (p = 0.003). MYBPC3 mutation carriers with ES-HC were older than patients with MYH7, other single mutations, or multiple mutations (median 41 vs 16, 26, and 28 years, p ≤0.001). Outcome of ES-HC patients was severe irrespective of genotype. In conclusion, the ES phase of HC is associated with a variable genetic substrate, not distinguishable from that of patients with HC and preserved EF, except for a higher frequency of complex genotypes with double or triple mutations of sarcomere genes.
    The American Journal of Cardiology 06/2014; 114(5). DOI:10.1016/j.amjcard.2014.05.065 · 3.43 Impact Factor
  • Molecular Genetics and Metabolism 02/2014; 111(2):S99. DOI:10.1016/j.ymgme.2013.12.242 · 2.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Low back pain (LBP) management is a critical public health issue in all developed countries. Most approaches show evidence of effects only in the short term. Aim: To identify predictors of functional outcome on discharge and at 1 year. Design: Prospective cohort study. Setting: Outpatient rehabilitation department. Population: Patients aged >18 addressed to exercise therapy for persisting LBP. Methods: The individually designed physiotherapy program provided 7 sessions (45'); patients were given advice to stay active and continue exercise program on discharge. Baseline (T0) assessment included: age, sex, time since onset, pain-related drug use, previous treatments, job, physical activity, pain (NRS) and Mental Health (SF36 sub-score); at follow-up (T2), we also enquired to on adherence to exercise prescription, physical activity, drugs. The primary outcome measure was the Roland and Morris Disability Questionnaire (RMDQ) patients scoring improvement >30% (minimal clinical important difference) were classified as respondent. Results: 211 completed follow-up (70% women; age 70.4±11.9). Average RMDQ score was reduced by 35% at T1 and by 31% at T2; NRS by 28% (T1) and 24% (T2); 125 patients (59%) were responders on discharge; 106 (50%) at follow-up. Only higher baseline NRS predicted poor response to treatment at T1 (OR=0.83, 95% CI: 0.71-0.95, P=0.012)). At T2, older age (OR=0.94, 95% CI: 0.91-0.98, P=0.003), drug use (OR=0.18, 95% CI: 0.08-4,69, P<0.001) and previous treatments (OR 0.33, 95% CI: 0.15 to 0.71, P=0.004) were significantly associated with poor response, while, baseline mental health (OR=1.1, 95% CI: 1.01-1.24, P=0.02) and adherence to exercises for LBP (OR=2.10, 95% CI: 1.03-4.42, P=0.04) predicted improved outcome. Conclusions: The individually designed exercise therapy program for chronic LBP was associated to clinically significant functional improvement both on discharge and at 1 year. Only severe pain intensity predicted poor treatment response on discharge. At one year, younger age and better mental health predicted improved outcome, while use of drugs and previous LBP treatments were associated with worse response. Adherence to the exercise program almost doubled the probability of a favorable outcome. Clinical Rehabilitation Impact: Adherence to an extensive individually designed exercise therapy program improves long term functional outcome of chronic low back pain.
    European journal of physical and rehabilitation medicine 01/2014; · 1.95 Impact Factor
  • Source
    Kardiologia polska 01/2014; 72(11):1054-126. DOI:10.5603/KP.2014.0212 · 0.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a complex cardiac condition characterized by variable degrees of asymmetric left ventricular (LV) hypertrophy, generally associated with mutations in sarcomere protein genes. While generally perceived as rare, HCM is the most common genetic heart disease with over one million affected individuals in Europe alone and represents a prevalent cause of sudden cardiac death in the young. To date, HCM remains an orphan disease, as recommended treatment strategies are based on the empirical use of old drugs with little evidence supporting their clinical benefit in this context. In the six decades since the original description of the disease, less than fifty pharmacological studies have been performed in HCM patients, enrolling little over 2,000 HCM patients, mostly comprising small non-randomized cohorts. No specific agent has been convincingly shown to affect outcome, and critical issues such as prevention of myocardial energy depletion, microvascular ischemia, progressive myocardial fibrosis and the peculiar mechanisms of arrhythmogenesis in HCM still need to be addressed in a systematic fashion. However, there is increasing evidence that a variety of drugs may counter the effects of sarcomere protein mutations and the resulting pathophysiological abnormalities at the molecular, cellular and organ level. Following major advances in our understanding of HCM and increasing opportunities for networking among large international referral centres, the opportunity now exists to identify potentially effective treatments and implement adequately designed pharmacological trials, with the ultimate aim to impact the natural course of the disease, alleviate symptoms and improve quality of life in our patients.
    09/2013; 2013(3):243-248. DOI:10.5339/gcsp.2013.31
  • [Show abstract] [Hide abstract]
    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.
    The American journal of cardiology 07/2013; 112(8). DOI:10.1016/j.amjcard.2013.06.018 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    European Journal of Heart Failure 06/2013; DOI:10.1093/eurjhf/hft104 · 6.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Whether uric acid (UA) serves as risk factor for cardiovascular diseases or as antioxidant defense has not yet been completely clarified. In this study we investigated the effects of UA on functional recovery in patients receiving cardiac rehabilitation. 306 patients, 209 men and 97 women, age range 25-87 years (mean 68 ± 11), performed the 6-min walk test (6mWT) before and after the rehabilitation, and the increase in walking distance was considered as the outcome measure of the study. Baseline UA serum levels ranged from 1.0 to 10.9 mg/dL (mean 5.2 ± 1.7). As there was a significant (p = 0.005) age*UA levels interaction, patients were divided into two subgroups, less then 65 years (n. 103, 68 men and 35 women, mean age 56 ± 9) and 65 years or more (n. 203, 141 men and 62 women, mean age 74 ± 5). After adjusting for relevant confounders, higher UA levels remained independent positive predictors of the increase in walking distance in older (p < 0.001) but not in younger patients (p = 0.807). Our findings show an independent association of higher UA levels with better functional recovery after cardiac rehabilitation selectively in elderly patients, suggesting that higher UA levels might reflect the decline in antioxidant defenses that occurs with advancing age. Future studies aimed at understanding the several contradictions concerning UA should, probably, address the issue within this perspective.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 06/2013; DOI:10.1016/j.numecd.2013.04.009 · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To assess the impact of body mass index (BMI) on cardiac phenotypic and clinical course in a multicenter HCM cohort. BACKGROUND: It is unresolved whether clinical variables promoting left ventricular (LV) hypertrophy in the general population, such as obesity, may influence cardiac phenotypic and clinical course in patients with hypertrophic cardiomyopathy (HCM). Therefore, we assessed the impact of body mass index (BMI) on disease expression in a multicenter HCM cohort. METHODS: In 275 adult HCM patients (age 48±14 years; 70% male), we assessed the relation of BMI to LV mass, determined by cardiovascular magnetic resonance (CMR) and heart failure progression. RESULTS: . At multivariate analysis, BMI proved independently associated with the magnitude of hypertrophy: pre-obese and obese HCM patients (BMI 25-30 and >30 kg/m(2), respectively) showed a 65% and 310% increased likelihood of an LV mass in the highest quartile (>120 g/m(2)), compared to normal weight patients (BMI <25; hazard ratio [HR] 1.65, 95%CI 0.73-3.74; p=0.22 and 3.1, 95%CI 1.42-6.86;p=0.004, respectively). Other features associated with LV mass >120 g/m(2) were LV outflow obstruction (HR 4.9; 95%CI 2.4-9.8; p<0.001), systemic hypertension (HR 2.2; 95%CI 1.1-4.5; p=0.026) and male gender (HR 2.1; 95%CI 0.9-4.7; p=0.083). During a median follow-up of 3.7 years (inter-quartile range 2.5-5.3), obese patients showed a 3.6 HR (95%CI 1.2-10.7; p=0.02) for developing NYHA class III-IV symptoms compared to non-obese patients, independent of outflow obstruction. Noticeably, the proportion of patients in NYHA class III at the end of follow-up was 13% among obese patients, compared to 6% among those of normal weight (p=0.03). CONCLUSIONS: In HCM patients, extrinsic factors such as obesity are independently associated with increase in LV mass and may dictate progression of heart failure symptoms.
    Journal of the American College of Cardiology 04/2013; 62(5). DOI:10.1016/j.jacc.2013.03.062 · 15.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac myosin binding protein-C (cMyBP-C) is a multi-domain (C0-C10) protein that regulates heart muscle contraction through interaction with myosin, actin and other sarcomeric proteins. Several mutations of this protein cause familial hypertrophic cardiomyopathy (HCM). Domain C1 of cMyBP-C plays a central role in protein interactions with actin and myosin. Here, we studied structure-function relationship of three disease causing mutations, Arg177His, Ala216Thr and Glu258Lys of the domain C1 using computational biology techniques with its available X-ray crystal structure. The results suggest that each mutation could affect structural properties of the domain C1, and hence it's structural integrity through modifying intra-molecular arrangements in a distinct mode. The mutations also change surface charge distributions, which could impact the binding of C1 with other sarcomeric proteins thereby affecting contractile function. These structural consequences of the C1 mutants could be valuable to understand the molecular mechanisms for the disease.
    PLoS ONE 03/2013; 8(3):e59206. DOI:10.1371/journal.pone.0059206 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The interruption of the manufacturing process of agalsidase beta has led to a worldwide shortage of this drug. In the EU, nearly all patients initially reduced their agalsidase beta dose, and many of these switched to agalsidase alfa (Replagal Shire HGT). The clinical consequences of this period of drug shortage need to be further evaluated. A gradual increase of agalsidase beta supply is now expected. This implies that patients could resume or even commence agalsidase beta treatment. Guidance for prioritization of patients is needed to support equitable distribution of agalsidase beta to EU member states. To achieve this, in absence of level I clinical evidence, a draft consensus proposal was initiated and distributed. No full consensus was achieved, as there is disagreement regarding the indications for switching patients from agalsidase alfa to agalsidase beta. Some physicians support the concept that the 1.0 mg/kg EOW dose of agalsidase beta is more effective than agalsidase alfa at 0.2 mg/kg EOW, while others believe that at recommended dose, the preparations are equivalent. In light of these difficulties and the uncertainties with respect to supply of agalsidase beta, recommendations were agreed upon by a subgroup of physicians. These current recommendations focus on prioritization of criteria indicative of disease progression.
    01/2013; 8:51-6. DOI:10.1007/8904_2012_160
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study comprised sarcomeric genotyping of the three most commonly involved sarcomeric genes: MYBPC3, MYH7, and TNNT2 in 192 unrelated Egyptian hypertrophic cardiomyopathy (HCM) index patients. Mutations were detected in 40 % of cases. Presence of positive family history was significantly (p = 0.002) associated with a higher genetic positive yield (49/78, 62.8 %). The majority of the detected mutations in the three sarcomeric genes were novel (40/62, 65 %) and mostly private (47/62, 77 %). Single nucleotide substitution was the most frequently detected mutation type (51/62, 82 %). Over three quarters of these substitutions (21/27, 78 %) involved CpG dinucleotide sites and resulted from C > T or G > A transition in the three analyzed genes, highlighting the significance of CpG high mutability within the sarcomeric genes examined. This study could aid in global comparative studies in different ethnic populations and constitutes an important step in the evolution of the integrated clinical, translational, and basic science HCM program.
    Journal of Cardiovascular Translational Research 12/2012; 6(4). DOI:10.1007/s12265-012-9425-0 · 2.69 Impact Factor
  • 12/2012; 2012(2):15. DOI:10.5339/gcsp.2012.15
  • Circulation Heart Failure 07/2012; 5(4):535-46. DOI:10.1161/CIRCHEARTFAILURE.112.967026 · 5.95 Impact Factor

Publication Stats

5k Citations
1,010.19 Total Impact Points


  • 2007–2014
    • University of Florence
      Florens, Tuscany, Italy
    • Tufts University
      Бостон, Georgia, United States
  • 2005–2014
    • Azienda Ospedaliero Universitaria Careggi
      Firenzuola, Tuscany, Italy
    • Istituto Superiore di Sanità
      Roma, Latium, Italy
  • 2008–2013
    • Fondazione Don Carlo Gnocchi
      Milano, Lombardy, Italy
    • Mayo Clinic - Rochester
      • Department of Cardiovascular Diseases
      Rochester, MN, United States
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom
  • 2012
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 2003–2009
    • Imperial College London
      Londinium, England, United Kingdom
    • Tufts Medical Center
      • Division of Cardiology
      Boston, Massachusetts, United States
  • 2000–2007
    • Minneapolis Heart Institute
      Minneapolis, Minnesota, United States
  • 2004
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • St George's, University of London
      Londinium, England, United Kingdom
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 1991–1996
    • Ospedale Pediatrico Meyer Firenze
      Florens, Tuscany, Italy
  • 1995
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
  • 1994
    • National Research Council
      Roma, Latium, Italy
  • 1993
    • Yale University
      New Haven, Connecticut, United States