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Piergiuseppe Agostoni,
Ugo Corrà,
Gaia Cattadori,
Fabrizio Veglia,
Rocco La Gioia,
Angela B Scardovi,
Michele Emdin,
Marco Metra,
Gianfranco Sinagra,
Giuseppe Limongelli, [......],
Annamaria Iorio,
Stefania Paolillo,
Pietro Palermo,
Mauro Contini,
Marco Confalonieri,
Pantaleo Giannuzzi,
Andrea Passantino,
Livio Dei Cas,
Massimo F Piepoli,
Claudio Passino
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ABSTRACT: OBJECTIVES: We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. BACKGROUND: HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. METHODS: Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. RESULTS: Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO(2) slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years. CONCLUSIONS: This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC.
International journal of cardiology 07/2012; · 7.08 Impact Factor
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ABSTRACT: AIMS: Most patients with hypertrophic cardiomyopathy (HCM) show a limited exercise capacity. A correlation between exercise tolerance and diastolic dysfunction has already been demonstrated. On the contrary, the role of rest-induced or exercise-induced obstruction as a determinant of exercise capacity is still open to debate. The aim of the present study was to analyse the exertional behaviour of patients with HCM presenting different left ventricle (LV) obstructive profiles. METHODS: Thirty-five consecutive patients with HCM (mean age 45 ± 14 years, 23 men) underwent echocardiography during cardiopulmonary exercise (CPX) testing. Non-invasive measurement of cardiac output was obtained with an inert gas rebreathing system at the beginning and at peak of exercise. RESULTS: Fifteen patients (43%) had neither resting nor provocable obstruction (group A: non-obstructive profile), 12 patients (34%) showed provocable obstruction during exercise (group B: latent-obstructive profile) and eight patients (23%) presented obstruction at rest (group C: rest-obstructive profile). Group A and B patients showed higher peak oxygen consumption in comparison with group C patients (24 ± 6 and 23 ± 6 vs. 17 ± 3 ml/kg per min; P = 0.016) and a greater increment of cardiac index during exercise (6.6 ± 1.3 and 6.0 ± 1.4 vs. 4.6 ± 0.8 l/min per m; P = 0.004). CONCLUSION: In comparison with the rest-obstructive profile, latent and non-obstructive HCM patients seem to share a similar exertional behaviour characterized by a greater increment of cardiac index during exercise and a minor impairment of exercise tolerance. Accordingly, in HCM patients not obstructive at rest, latent obstruction cannot be suspected based on exertional behaviour and functional capacity. Echocardiography performed during CPX test providing an important adjunct, may be valuable in guiding treatment in patients with substantial exercise limitation.
Journal of Cardiovascular Medicine 06/2012; · 1.51 Impact Factor
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Journal of Cardiovascular Electrophysiology 04/2012; 23(8):882-883. · 3.06 Impact Factor
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Katja Gehmlich,
Angeliki Asimaki,
Thomas J Cahill,
Elisabeth Ehler,
Petros Syrris,
Elisabetta Zachara, Federica Re,
Andrea Avella,
Lorenzo Monserrat,
Jeffrey E Saffitz,
William J McKenna
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ABSTRACT: The diagnosis of arrhythmogenic right ventricular cardiomyopathy can be challenging. Disease-causing mutations in desmosomal genes have been identified. A novel diagnostic feature, loss of immunoreactivity for plakoglobin from the intercalated disks, recently was proposed.
The purpose of this study was to identify two novel mutations in the intracellular cadherin segment of desmoglein-2 (G812S and C813R in exon 15). Co-segregation of the G812S mutation with disease expression was established in a large Caucasian family. Endomyocardial biopsies of two individuals showed reduced plakoglobin signal at the intercalated disk.
To understand the pathologic changes occurring in the diseased myocardium, functional studies on three mutations in exon 15 of desmoglein-2 (G812C, G812S, C813R) were performed.
Localization studies failed to detect any differences in targeting or stability of the mutant proteins, suggesting that they act via a dominant negative mechanism. Binding assays were performed to probe for altered binding affinities toward other desmosomal proteins, such as plakoglobin and plakophilin-2. Although no differences were observed for the mutated proteins in comparison to wild-type desmoglein-2, binding to plakophilin-2 depended on the expression system (i.e., bacterial vs mammalian protein expression). In addition, abnormal migration of the C813R mutant protein was observed in gel electrophoresis.
Loss of plakoglobin immunoreactivity from the intercalated disks appears to be the endpoint of complex pathologic changes, and our functional data suggest that yet unknown posttranslational modifications of desmoglein-2 might be involved.
Heart rhythm: the official journal of the Heart Rhythm Society 10/2010; 7(10):1446-53. · 4.56 Impact Factor
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Piergiuseppe Agostoni,
Michele Emdin,
Ugo Corrà,
Fabrizio Veglia,
Damiano Magrì,
Calogero C Tedesco,
Emanuela Berton,
Claudio Passino,
Erika Bertella, Federica Re, [......],
Rocco La Gioia,
Marco Vicenzi,
Alberto Giannoni,
Domenico Scrutinio,
Pantaleo Giannuzzi,
Claudio Tondo,
Andrea Di Lenarda,
Gianfranco Sinagra,
Massimo F Piepoli,
Marco Guazzi
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ABSTRACT: The influence of permanent atrial fibrillation on exercise tolerance and cardio-respiratory function during exercise in heart failure (HF) is unknown.
We retrospectively compared the results of 942 cardiopulmonary exercise tests, performed consecutively at seven Italian laboratories, in HF patients with atrial fibrillation (n = 180) and sinus rhythm (n = 762). By multivariable logistic regression analysis, peak VO(2) (OR 0.376, 95% CI 0.240-0.588, P < 0.0001), O(2)pulse (VO(2)/heart rate, HR) (OR 0.236, 95% CI 0.152-0.366, P < 0.0001), VCO(2) (OR 3.97, 95% CI 2.163-7.287, P < 0.0001), and ventilation (OR 1.38, 95% CI 1.045-1.821, P = 0.0231) were independently associated with atrial fibrillation. Anaerobic threshold (AT) was identified in 132 of 180 (73%) atrial fibrillation and in 649 of 762 (85%) sinus rhythm patients (P = 0.0002). By multivariable logistic regression analysis, only peak VO(2) (OR 0.214, 95% CI 0.155-0.296, P < 0.0001) was independently associated with unidentified AT. At AT, atrial fibrillation HF patients had higher HR (P < 0.0001) and higher VO(2) (P < 0.001) compared with sinus rhythm HF patients. Among AT variables, by multivariable logistic regression analysis, only HR was an independent predictor of atrial fibrillation.
In HF patients with permanent atrial fibrillation, exercise performance is reduced as reflected by reduced peak VO(2). The finding of unidentified AT is associated with a poor performance. In atrial fibrillation patients, VO(2) is higher at AT whereas lower at peak. This last observation raises uncertainties about the use of AT data to define performance and prognosis of HF patients with atrial fibrillation.
European Heart Journal 09/2008; 29(19):2367-72. · 10.48 Impact Factor
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Iacopo Olivotto,
Francesca Girolami,
Michael J Ackerman,
Stefano Nistri,
J Martijn Bos,
Elisabetta Zachara,
Steve R Ommen,
Jeanne L Theis,
Rachael A Vaubel, Federica Re,
Corinna Armentano,
Corrado Poggesi,
Francesca Torricelli,
Franco Cecchi
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ABSTRACT: To determine the influence of a positive genetic test for hypertrophic cardiomyopathy (HCM) on clinical outcome.
A cohort of 203 unrelated patients with HCM (mean +/- SD age, 50+/-18 years) was enrolled from January 1, 2002, through December 31, 2003. They were followed up for a mean +/- SD time of 4.0+/-1.7 years after genetic testing of the 8 HCM-susceptibility genes that encode key sarcomeric/myofilament proteins. The clinical phenotype of those with a positive genetic test (myofilament-positive HCM) was compared with those with a negative genetic test (myofilament-negative HCM).
In this cohort of 203 patients, 87 mutations were identified in 126 patients (myofilament-positive HCM, 62%); the remaining 77 patients (38%) were myofilament-negative. Despite similar baseline features, patients with myofilament-positive HCM showed increased risk of the combined end points of cardiovascular death, nonfatal stroke, or progression to New York Heart Association class III or IV compared with the patients with myofilament-negative HCM (25% vs 7%, respectively; independent hazard ratio, 4.27; P=.008). These end points occurred at any age among patients with myofilament-positive HCM (range, 14-86 years), but only in those aged 65 years and older among patients with myofilament-negative HCM. Moreover, patients with myofilament-positive HCM showed greater probability of severe left ventricular systolic and diastolic dysfunction, defined as an ejection fraction of less than 50% and a restrictive filling pattern (P=.02 and P<.02, respectively, vs myofilament-negative HCM).
Screening for sarcomere protein gene mutations in HCM identifies a broad subgroup of patients with increased propensity toward long-term impairment of left ventricular function and adverse outcome, irrespective of the myofilament (thick, intermediate, or thin) involved.
Mayo Clinic Proceedings 07/2008; 83(6):630-8. · 5.70 Impact Factor
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Andrea Avella,
Giulia d'Amati,
Augusto Pappalardo, Federica Re,
Paola Francesca Silenzi,
Francesco Laurenzi,
Piergiuseppe DE Girolamo,
Gemma Pelargonio,
Antonio Dello Russo,
Pasquale Baratta,
Giuseppe Messina,
Paolo Zecchi,
Elisabetta Zachara,
Claudio Tondo
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ABSTRACT: Voltage Mapping-Guided Biopsy in ARVC/D.
To improve the endomyocardial biopsy (EMB) diagnostic sensitivity for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), we hypothesized a biopsy sampling focused on selected right ventricle (RV) low-voltage areas identified by electroanatomic voltage mapping.
The study population (22 patients, 10 men; mean age 34 +/- 10 years) included 11 patients with overt ARVC/D (group A) and 11 patients with suspected ARVC/D (group B), according to both arrhythmic profile and standardized noninvasive diagnostic criteria. In all 22 patients, an RV bipolar voltage mapping was performed with CARTO system sampling multiple endocardial sites (262 +/- 61), during sinus rhythm, with a 0.5-1.5 mV color range setting of voltage display. All 11 (100%) group A patients and 8 of the 11 (73%) group B patients (P = nonsignificant [NS]) presented RV low-voltage areas (<0.5 mV). In 8 group A patients and in all 8 group B patients with a pathological RV voltage map, an EMB focused on the low-voltage areas was performed. In 6 (75%) group A patients and in 7 (87%) group B patients (P = NS), voltage mapping-guided EMB was diagnostic for ARVC/D. In the remaining 3 patients, only nonspecific histological findings were observed.
The results of our study (1) confirm the high diagnostic sensitivity of RV voltage mapping in patients with overt ARVC/D, (2) document a high prevalence of RV low-voltage areas even in patients with suspected ARVC/D, and (3) demonstrate that in patients with clinical evidence or suspicion for ARVC/D, presenting RV low-voltage areas, EMB guided by voltage mapping may provide ARVC/D diagnosis confirmation.
Journal of Cardiovascular Electrophysiology 06/2008; 19(11):1127-34. · 3.06 Impact Factor
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ABSTRACT: A positive endomyocardial biopsy (EMB) is a major diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC). Nevertheless, its sensitivity is low due to the focal nature of the disease. Moreover, myocardial samples are usually taken from the uncommonly involved interventricular septum to minimize the risk of perforation. In this report, we describe a novel bioptical approach for ARVC diagnosis guided by the identification of right ventricle (RV) affected regions by means of electroanatomical voltage mapping.
Journal of Cardiovascular Electrophysiology 09/2007; 18(9):991-3. · 3.06 Impact Factor
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ABSTRACT: Mutations causing hypertrophic cardiomyopathy (HCM) have been described in nine different genes of the sarcomere. Three genes account for most known mutations: beta-myosin heavy chain (MYH7), cardiac myosin binding protein C (MYBPC3) and cardiac troponin T (TNNT2). Their prevalence in Italian HCM patients is unknown. Thus, we prospectively assessed a molecular screening strategy of these three genes in a consecutive population with HCM from two Italian centres.
Comprehensive screening of MYBPC3, MYH7 and TNNT2 was performed in 88 unrelated HCM patients by denaturing high-performance liquid chromatography and automatic sequencing.
We identified 32 mutations in 50 patients (57%); 16 were novel. The prevalence rates for MYBPC3, MYH7 and TNNT2 were 32%, 17% and 2%, respectively. MYBPC3 mutations were 18, including two frameshift, five splice-site and two nonsense. All were 'private' except insC1065 and R502Q, present in three and two patients, respectively. Moreover, E258K was found in 14% of patients, suggesting a founder effect. MYH7 mutations were 12, all missense; seven were novel. In TNNT2, only two mutations were found. In addition, five patients had a complex genotype [i.e. carried a double MYBPC3 mutation (n = 2), or were double heterozygous for mutations in MYBPC3 and MYH7 (n = 3)].
The first comprehensive evaluation of MYBPC3, MYH7 and TNNT2 in an Italian HCM population allowed a genetic diagnosis in 57% of the patients. These data support a combined analysis of the three major sarcomeric genes as a rational and cost-effective initial approach to the molecular screening of HCM.
Journal of Cardiovascular Medicine 09/2006; 7(8):601-7. · 1.51 Impact Factor
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ABSTRACT: The aim of the study is to verify: 1) the trustworthiness level of the diagnosis of AMI defined in Emergency Department (ER); 2) the frequency and the effectiveness (length of staying in hospital, mortality rate) of the invasive or not invasive treatment which are implemented in the ER area.
We have studied the crowding of the patients suffering from chest pain (CP) who asked the ER for assistance during the year 2000 and that of the patients with AMI diagnosed in ER (diagnosis at the admittance and at the discharge from the hospital, therapeutic procedures, staying in hospital, mortality rate).
The patients suffering from CP have been the 5.4% of all the patients who reached the ER and were admitted to the hospital more than the patients who reached the ER for all the other causes (41.5% versus 22.1%). In 61.7% of the patients affected by AMI the disease was identified by the physicians of the ER; the invasive treatment has been developed in 67.7% of those patients and the not invasive in 32.3% of the same patients. The mean length of the staying in hospital for the patients who have been treated with PTCA was 10.3 days; on the contrary, the same value for the patients treated with thrombolysis was 13.8 days and the difference was significant at the 0.001 level. The mortality rate during the staying in Hospital was 5.9% in the patients treated with PTCA and 13% in the patients treated with thrombolysis but the difference was not significant because of the little number of the dead patients.
The sensitivity (62%) and the specificity (100%) of the diagnosis of AMI defined in the ER demonstrate the utility of a Cardiologic Service in ER.
Recenti progressi in medicina 11/2002; 93(10):523-8.
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ABSTRACT: Sudden cardiac death (SCD) is one of the most common causes of death in developed countries. In Italy, an annual incidence of 0.7 per 1000 inhabitants per year can be estimated. SCD represents the main cause of sudden death in children, adolescents and young adults and often occurs in young and previously asymptomatic patients. This issue has acquired even greater relevance since implantable cardioverter-defibrillators have proved to be highly effective in preventing sudden death in high-risk subjects. Autopsy findings of young SCD victims include inherited cardiac disorders with a defined morphologic substrate but also hearts without any identifiable structural abnormalities (sudden unexplained death). The potential heritability of the underlying disorder makes surviving relatives at risk of sudden death. A cardiological workup in these families may allow identification of cardiac disease and may unmask affected surviving relatives in whom the disease had remained unrecognized. Cardiological and genetic assessment of relatives of SCD victims based on current literature is reported in this review as well as our experience on SCD in young people in the Lazio Region (Italy) between 2001 and 2008.
Giornale italiano di cardiologia (2006) 11(7-8):557-65.
