Franco Cecchi

Azienda Ospedaliero Universitaria Careggi, Florens, Tuscany, Italy

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Publications (205)1165.04 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: Background: Subcutaneous ICD (S-ICD) is a promising option for hypertrophic cardiomyopathy (HCM) patients. HCM patients can present markedly abnormal electrocardiograms (ECG) and there are no data regarding which percentage of HCM patients fail the prerequisite S-ICD vector screening. Objectives: To determine the failure rate of the prerequisite vector screening using one or two acceptable vectors stratified for risk profile for SCD and predictors of failure. Methods: ECG recordings from consecutive HCM patients simulating the S-ICD sensing vectors were analyzed with the S-ICD screening tool. Eligibility was defined by 1 or 2 appropriate vectors. Medical history, ultrasound and 12 lead ECG characteristics were analyzed and the individual arrhythmic risk at 5 year was determined, to study potential predictors for failure. Results: One hundred sixty-five (118 males, age 51±16 years) were analyzed. Twenty-two (13%) patients had a high risk of SCD, 33 (20%) had intermediate to high risk and 110 (67%) were low risk. A total of 26 (16%) patients had no suitable vector, including 8/22 (36%) high risk patients. The primary cause of failure was high T-wave voltages in 25% of vectors analyzed. T wave inversions in more than two leads on surface 12-lead ECG (OR 15.6; p<0.001; CI 4.9-50.3) and prior myectomy (OR 8.4; p=0.002; CI 2.1-33.1) were significantly associated with screening failure in a multivariable model. Conclusions: Current available pre-implant screening algorithms recommended by the manufacturer are associated with a significant failure rate in HCM patients, particularly in the high-risk subgroup.
    Full-text · Article · Sep 2015 · Heart rhythm: the official journal of the Heart Rhythm Society
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    ABSTRACT: Transmural abnormalities in myocardial blood flow (MBF) are important causes of ischaemia in patients with left ventricular (LV) hypertrophy. The study aimed to test whether pixel-wise parametric mapping of (13)NH3 MBF can reveal transmural abnormalities in patients with hypertrophic cardiomyopathy (HCM). We submitted 11 HCM patients and 9 age-matched controls with physiological LV hypertrophy to rest and stress (dipyridamole) (13)NH3 PET. We measured MBF using a compartmental model, and obtained rest and stress parametric maps. Pixel MBF values were reorganized to obtain subendocardial and subepicardial MBF of LV segments. MBF at rest was higher in the subendocardial than in the subepicardial layer: 0.78 ± 0.19 vs. 0.60 ± 0.18 mL/min/g in HCM patients; 0.92 ± 0.24 vs. 0.75 ± 0.24 mL/min/g in controls (both p < 0.0001). Transmural perfusion gradient (TPG = subendocardial MBF/subepicardial MBF) at rest was similar: 1.35 ± 0.31 in HCM patients; 1.28 ± 0.27 in controls (NS). During stress, controls maintained higher subendocardial MBF: 2.44 ± 0.54 vs. 1.96 ± 0.67 mL/min/g tissue (p < 0.0001), with a TPG of 1.33 ± 0.35 (NS vs. rest). In HCM patients, the difference between subendocardial and subepicardial MBF was reduced (1.46 ± 0.48 vs. 1.36 ± 0.48 mL/min/g tissue, p < 0.01) and TPG decreased to 1.11 ± 0.34 (p < 0.0001 vs. rest and vs. controls). In HCM patients 8 of 176 segments had subendocardial MBF less than -2 × SD of the mean, versus none of 144 segments in controls (p < 0.01). Pixel-wise parametric mapping of (13)NH3 MBF enables the identification of transmural abnormalities in patients with HCM.
    No preview · Article · Jun 2015 · European Journal of Nuclear Medicine
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    ABSTRACT: Mutations in the gene coding for cardiac myosin binding protein-C (cMyBP-C), a multi-domain (C0-C10) protein, are a major causative factor for inherited hypertrophic cardiomyopathy. Patients carrying mutations in this gene have an extremely heterogeneous clinical course, with some progressing to end-stage heart failure. The cause of this variability is unknown. We here describe molecular modeling of a double mutation in domains C1 (E258K) and C2 (E441K) in a patient with severe HCM phenotype. The three-dimensional structure for the C1-motif-C2 complex was constructed with double and single mutations being introduced. Molecular dynamic simulations were performed for 10 ns under physiological conditions. The results showed that both E258K and E441K in isolation can predominantly affect the native domain as well as the nearby motif via conformational changes and result in an additive effect when they coexist. These changes involve important regions of the motif such as phosphorylation and potential actin-binding sites. Moreover, the charge reversal mutations altered the surface electrostatic properties of the complex. In addition, we studied protein expression, which showed that the mutant proteins were expressed and we can suppose that the severe phenotype was not due to haploinsufficiency. However, additional studies on human gene expression will need to confirm this hypothesis. The double mutation affecting the regulatory N-terminal of cMyBP-C have the potential of synergistically interfering with the binding to neighbouring domains and other sarcomeric proteins. These effects may account for the severe phenotype and clinical course observed in the complex cMyBP-C genotypes.
    No preview · Article · May 2015 · Journal of Cardiovascular Translational Research
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    ABSTRACT: 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. 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. 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. 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.
    Full-text · Article · Mar 2015 · Orphanet Journal of Rare Diseases
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    I G Aprile · C Briani · C Pazzaglia · F Cecchi · S Negrini · L Padua
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    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.
    Full-text · Article · Feb 2015 · European journal of physical and rehabilitation medicine
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    Full-text · Article · Feb 2015 · Journal of Cardiovascular Magnetic Resonance
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    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).
    No preview · Article · Jan 2015 · Revista Espa de Cardiologia

  • No preview · Article · Jan 2015
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    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.
    Preview · Article · Dec 2014 · Journal of the American College of Cardiology
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    Full-text · Article · Dec 2014 · Kardiologia polska
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    ABSTRACT: Background: Screening in subjects with left ventricular hypertrophy (LVH) reveals a high prevalence of Fabry disease (FD). Often, a diagnosis is uncertain because characteristic clinical features are absent and genetic variants of unknown significance (GVUS) in the α-galactosidase A (GLA) gene are identified. This carries a risk of misdiagnosis, inappropriate counselling and extremely expensive treatment. We developed a diagnostic algorithm for adults with LVH (maximal wall thickness (MWT) of >12 mm), GLA GVUS and an uncertain diagnosis of FD. Methods: A Delphi method was used to reach a consensus between FD experts. We performed a systematic review selecting criteria on electrocardiogram, MRI and echocardiography to confirm or exclude FD. Criteria for a definite or uncertain diagnosis and a gold standard were defined. Results: A definite diagnosis of FD was defined as follows: a GLA mutation with ≤ 5% GLA activity (leucocytes, mean of reference value, males only) with ≥ 1 characteristic FD symptom or sign (neuropathic pain, cornea verticillata, angiokeratoma) or increased plasma (lyso)Gb3 (classical male range) or family members with definite FD. Subjects with LVH failing these criteria have a GVUS and an uncertain diagnosis. The gold standard was defined as characteristic storage in an endomyocardial biopsy on electron microscopy. Abnormally low voltages on ECG and severe LVH (MWT>15 mm) <20 years exclude FD. Other criteria were rejected due to insufficient evidence. Conclusions: In adults with unexplained LVH and a GLA GVUS, severe LVH at young age and low voltages on ECG exclude FD. If absent, an endomyocardial biopsy with electron microscopy should be performed.
    Full-text · Article · Dec 2014 · International Journal of Cardiology

  • No preview · Conference Paper · Oct 2014
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    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 α-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.
    Preview · Article · Aug 2014 · Circulation Cardiovascular Genetics
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    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.
    Full-text · Article · Aug 2014 · Circulation
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    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.
    Full-text · Article · Jun 2014 · The American Journal of Cardiology

  • No preview · Article · Feb 2014 · Molecular Genetics and Metabolism
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    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.
    No preview · Article · Jan 2014 · European journal of physical and rehabilitation medicine
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    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.
    Full-text · Article · Sep 2013

Publication Stats

6k Citations
1,165.04 Total Impact Points


  • 2005-2015
    • Azienda Ospedaliero Universitaria Careggi
      • Department of Nuclear Medicine
      Florens, Tuscany, Italy
  • 1984-2015
    • University of Florence
      • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      Florens, Tuscany, Italy
  • 2008-2014
    • Fondazione Don Carlo Gnocchi
      Milano, Lombardy, Italy
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom
  • 2012
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 2004-2009
    • Imperial College London
      Londinium, England, United Kingdom
  • 1999-2007
    • Minneapolis Heart Institute
      Minneapolis, Minnesota, United States
  • 1996
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      Ancona, The Marches, Italy
  • 1992-1996
    • 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
      • Section of Cardiovascular Medicine
      New Haven, Connecticut, United States