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Marcello Disertori,
Maria Grazia Franzosi,
Simona Barlera,
Franco Cosmi,
Silvia Quintarelli,
Chiara Favero,
Glauco Cappellini,
Gianna Fabbri,
Aldo Pietro Maggioni,
Lidia Staszewsky,
Luigi Andrea Moroni,
Roberto Latini
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ABSTRACT: BACKGROUND: Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. METHODS: We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences -- where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. RESULTS: Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41+/-0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). CONCLUSIONS: TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF.Trial registration: GISSI-AF study: Clinical Trials.gov Identifier: NCT00376272.
BMC Cardiovascular Disorders 04/2013; 13(1):28. · 1.52 Impact Factor
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Antonio Raviele, Marcello Disertori,
Paolo Alboni,
Emanuele Bertaglia,
Gianluca Botto,
Michele Brignole,
Riccardo Cappato,
Alessandro Capucci,
Maurizio Del Greco,
Roberto De Ponti,
Matteo Di Biase,
Giuseppe Di Pasquale,
Michele Gulizia,
Federico Lombardi,
Sakis Themistoclakis,
Massimo Tritto
Giornale italiano di cardiologia (2006) 03/2013; 14(3):215-40.
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ABSTRACT: Atrial fibrillation (AF) is the commonest sustained arrhythmia in clinical practice, but its treatment is still a challenge for modern cardiology. During the last decade new insights regarding AF genetic background have been achieved. Familial aggregation suggesting a potential heritability was well known in the pre-molecular era. Now, research on the molecular basis of the disease is providing evidence that familial AF is mostly autosomal, both dominant and recessive, and genetically heterogeneous. Mutations in several disease genes with different functional effects may be associated with AF. Early results encourage family studies and monitoring. In addition, genome-wide association studies have recently identified common polymorphisms associated with an increased risk of AF in different large populations. These studies are contributing to provide early answers, but also raise new questions. In this review we analyze existing knowledge on genetics of AF and related potential clinical impact.
Giornale italiano di cardiologia (2006) 01/2013; 14(1):46-54.
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Marcello Disertori,
Silvia Quintarelli,
Maurizia Grasso,
Andrea Pilotto,
Nupoor Narula,
Valentina Favalli,
Camilla Canclini,
Marta Diegoli,
Silvia Mazzola,
Massimiliano Marini,
Maurizio Del Greco,
Roberto Bonmassari,
Michela Masè,
Flavia Ravelli,
Claudia Specchia,
Eloisa Arbustini
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ABSTRACT: BACKGROUND: -Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983 we described 8-years follow-up of idiopathic atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from a same geographic area in the North-East Italy. METHODS AND RESULTS: -We followed-up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives and investigated the genetic basis of the disease. The disease was characterized by: 1) clinical onset in adulthood; 2) bi-atrial dilatation up to giant size; 3) early supraventricular arrhythmias with progressive loss of atrial electrical activity to atrial standstill; 4) thromboembolic complications; 5) stable, normal left ventricular function and NYHA functional class during the long-term course of the disease. By linkage analysis we mapped a locus at 1p36.22 containing the natriuretic precursor A (NPPA) gene. By sequencing NPPA we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of Atrial Natriuretic Peptide (ANP). Heterozygous mutation carriers were healthy and demonstrated normal levels of ANP. CONCLUSIONS: -Autosomal recessive Atrial Dilated Cardiomyopathy is a rare disease associated with homozygous mutation of the NPPA gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function and severely decreased levels of ANP.
Circulation Cardiovascular Genetics 12/2012; · 6.11 Impact Factor
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ABSTRACT: The aim of this study was to investigate the anatomic distribution of critical sources in patients with atrial fibrillation (AF) by fusion of biatrial computed tomography (CT) images with cycle length (CL) and wave similarity (WS) maps.
Experimental and clinical studies show that atrial fibrillation (AF) may originate from rapid and repetitive (RR) sources of activation. Localization of RR sources may be crucial for an effective ablation treatment. Atrial electrograms showing rapid and repetitive activations can be identified by combining WS and CL analysis.
Patients with persistent AF underwent biatrial electroanatomic mapping and pre-procedural CT cardiac imaging. WS and CL maps were constructed in 17 patients by calculating the degree of repetitiveness of activation waveforms (similarity index [S]) and the cycle length at each atrial site. WS/CL maps were then integrated with biatrial 3-dimensional CT reconstructions by a stochastic approach.
Repetitive sources of activation (S ≥0.5) were present in most patients with persistent AF (94%) and were mainly located at the pulmonary veins (82% of patients), at the superior caval vein (41%), on the anterior wall of the right atrium (23%), and at the left atrial appendage (23%). Potential driver sources showing both rapid and repetitive activations (CL = 140.7 ± 25.1 ms, S = 0.65 ± 0.15) were present only in a subset of patients (65%) and were confined to the pulmonary vein region (47% of patients) and left atrial appendage (12%). Differently, the repetitive activity of the superior caval vein was characterized by a slow activation rate (CL = 184.7 ± 14.6 ms).
The identification and localization of RR sources is feasible by fusion of biatrial anatomic images with WS/CL maps. Potential driver sources are present only in a subset of patients with persistent AF and are mainly located in the pulmonary vein region.
JACC. Cardiovascular imaging 12/2012; 5(12):1211-20. · 14.29 Impact Factor
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Giornale italiano di cardiologia (2006) 05/2012; 13(5):309-13.
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ABSTRACT: To analyze the published data on the role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs) in secondary prevention of AF. Some post-hoc analyses from trials in different clinical scenarios suggested the efficacy of ACEIs and ARBs in the prevention of new onset atrial fibrillation (AF), while their efficacy in preventing AF recurrences is notably controversial.
The authors reviewed all published prospective, randomized vs. placebo or no-treatment studies, concerning the effect of ACEIs and ARBs in the prevention of AF recurrences. Four ACEIs studies accounting for a total of 355 patients and six ARBs studies comprising 4.040 patients were analyzed.
The pooled ACEIs data showed a statistical significant effect in preventing AF recurrences. However, the studies did not have a robust follow-up algorithm to recognize AF episodes, and were individually very small. On the contrary, pooled ARBs data did not show any effect in preventing AF recurrences (RR 0.90; 95% CI, 0.75-1.08; p = 0.24). The ARBs analyzed population was much larger in three large prospective, randomized, double-blind, placebo-control trials with transtelephoning monitoring of AF recurrences and neutral results. The meta-analysis of ACEIs and ARBs trials together could suggest a publication bias that may result in an overestimation of the treatment effect.
Currently there is no role for ARBs in secondary prevention of AF. With regard to ACEIs, the data are not strong enough for a conclusion, although the efficacy is expected to be the same as that of ARBs.
Cardiovascular Drugs and Therapy 02/2012; 26(1):47-54. · 3.13 Impact Factor
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Lidia Staszewsky,
Maylene Wong,
Serge Masson,
Elena Raimondi,
Silvana Gramenzi,
Gianni Proietti,
Dario Bicego,
Carlo Emanuelli,
Giancarlo Pulitanò,
Filippo Taddei,
Enrico B Nicolis,
Ernesto Correale,
Gianna Fabbri,
Federico Bertocchi,
Maria Grazia Franzosi,
Aldo P Maggioni,
Gianni Tognoni, Marcello Disertori,
Roberto Latini
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ABSTRACT: Left atrial (LA) dilation precedes or appears early after the onset of atrial fibrillation (AF) and factors in perpetuating the arrhythmia. Angiotensin receptor blockers were proposed for reversing LA remodeling. We evaluated the effect of valsartan on LA remodeling in patients with a recent episode of AF and the effect of LA size on AF recurrence (AFr).
LA and left ventricular (LV) echocardiographic variables were measured at baseline and 6 and 12 months in 340 patients from GISSI-AF, a trial testing valsartan prevention of AFr. Reversal of remodeling was considered as a decrease in LA size over 12 months. Changes in patients with and without recurrence and the relationship to duration of AFr were analyzed. Patients were 68.4±8.8 years old, with history of hypertension (85.3%) and cardioversion in the previous 2 weeks (87.4%) or ≥2 AFr in the previous 6 months (40.4%). Baseline LA maximal volume (LAVmax) was severely increased (>40 mL/m(2)); LV dimensions and function were relatively normal. Over 12 months, 54.4% of patients had AFr. LAVmax was unchanged by rhythm, time, or randomized treatment. Higher baseline LAVmax and lower LA emptying fraction were linearly related to increasing AFr duration during follow-up.
GISSI-AF patients in sinus rhythm and history of AF showed severely increased LAVmax with mostly normal LV volume, mass, and systolic and diastolic function. Valsartan for 1 year did not reverse LA remodeling or prevent AFr. Half of the patients without AFr had severe LA dilation; therefore, mechanisms other than structural remodeling triggered recurrence.
Circulation Cardiovascular Imaging 09/2011; 4(6):721-8. · 5.94 Impact Factor
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Marcello Disertori,
Federico Lombardi,
Simona Barlera,
Aldo Pietro Maggioni,
Chiara Favero,
Maria Grazia Franzosi,
Donata Lucci,
Lidia Staszewsky,
Gianna Fabbri,
Silvia Quintarelli,
Leopoldo Bianconi,
Roberto Latini
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ABSTRACT: Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm. In a consistent percentage of cases, AF recurrences are asymptomatic, thus making its clinical management difficult in relation to both therapeutic efficacy and thromboembolic risk.
The GISSI-AF trial enrolled 1,442 patients in sinus rhythm with previous AF episodes. Patients were randomized to valsartan or placebo and followed for 12 months. To improve the likelihood of detecting arrhythmic recurrences, arrhythmic follow-up was based on both programmed or symptom-related control visits and transtelephonic electrocardiographic transmissions. The present post hoc analysis was performed on 1,638 arrhythmic episodes that occurred in 623 patients.
Asymptomatic AF recurrences were present in 49.5% of patients. In multivariable analysis, asymptomatic AF recurrences were significantly associated with a longer duration of qualifying arrhythmias (odds ratio [95% CI] 1.57 (1.26-1.97), P < .0001). A lower ventricular response (P < .001) and a longer duration of the arrhythmic recurrence (P < .001) characterized asymptomatic episodes. Patients with asymptomatic events were more likely to be in AF at the time of electrocardiographic control at the end of the 12-month follow-up (adjusted odds ratio [95% CI] 4.9 (2.8-8.4), P < .001). Moreover, a higher CHADS(2) (Congestive heart failure, history of Hypertension, Age≥75 years, Diabetes mellitus, and past history of Stroke or TIA doubled) score and a more frequent use of amiodarone, calcium-channel blockers, and digitalis characterized patients with asymptomatic, whereas 1C drugs were more often used in subjects with symptomatic recurrences.
Asymptomatic AF recurrences were frequent in the GISSI-AF study population in patients who were more likely to develop persistent-permanent AF and were characterized by an increased thromboembolic risk.
American heart journal 08/2011; 162(2):382-9. · 4.65 Impact Factor
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Journal of Cardiovascular Medicine 05/2011; 12(5):374; author reply 375. · 1.51 Impact Factor
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Marcello Disertori
Giornale italiano di cardiologia (2006) 05/2011; 12(5):374-8; discussion 378.
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Antonio Raviele, Marcello Disertori,
Paolo Alboni,
Emanuele Bertaglia,
Gianluca Botto,
Michele Brignole,
Riccardo Cappato,
Alessandro Capucci,
Maurizio Del Greco,
Roberto De Ponti,
Matteo Di Biase,
Giuseppe Di Pasquale,
Michele Gulizia,
Federico Lombardi,
Sakis Themistoclakis,
Massimo Tritto
Giornale italiano di cardiologia (2006) 01/2011; 12(1 Suppl 1):7-69.
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Giornale italiano di cardiologia (2006) 11/2010; 11(11):795-9.
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ABSTRACT: The mechanisms by which atrial stretch favors the development of a substrate for atrial fibrillation (AF) are not fully understood. In this study, the role of stretch-induced conduction changes in the creation of a proarrhythmic substrate has been investigated by quantifying the spatial distribution of local conduction velocities (CVs) in the human atrium during acute atrial dilatation.
Electroanatomic mapping of right atrial activation was performed in 10 patients during coronary sinus pacing under control condition and during acute atrial dilatation. Atrial stretch was obtained by simultaneous atrioventricular (AV) pacing at a cycle length of 450-500 ms. Local CVs were accurately estimated by applying the principle of triangulation and spatially mapped over the whole right atrial endocardial surface. Simultaneous AV pacing significantly increased right atrial volume from 72.0 ± 29.0 to 86.3 ± 31.3 mL (P < 0.001). The 23% increase in atrial volume resulted in an overall decrease in atrial CV from 65.8 ± 5.9 to 55.2 ± 7.2 cm/s (P < 0.001) and an increased incidence of slow conduction sites or local conduction blocks from 10.3 ± 4.2% to 15.9 ± 7.7% (P < 0.01). Acute atrial dilatation concurrently increased AF vulnerability, with 6 of 10 patients developing AF episodes under stretch condition.
Quantification of stretch-induced conduction changes in the human atrium is feasible by combining simultaneous AV pacing and CV map construction. Acute atrial dilatation results in conduction slowing and significant increase in AF vulnerability, suggesting the role of stretch-induced conduction disturbances in the creation of a substrate for AF.
Journal of Cardiovascular Electrophysiology 11/2010; 22(4):394-401. · 3.06 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is a very common arrhythmia. Currently available tools to control arrhythmic recurrences (antiarrhythmic agents, catheter ablation) are not entirely satisfactory. Recently attention has been directed to upstream therapy, in order to alter the arrhythmia substrate; the most promising drugs seem to be those targeting the renin-angiotensin-aldsterone system. Several post-hoc analyses from large trials, in different clinical situations, confirmed the efficacy of angiotensin-converting enzyme-inhibitors and angiotensin II receptor blockers in primary prevention of AF. On the contrary prospective randomized, placebo-controlled, and double-blind studies showed negative results as for secondary prevention of AF. The GISSI-AF trial, the largest study (1442 patients) dealing with the use of angiotensin II receptor blockers in prevention of AF recurrences, has not demonstrated any difference between patients treated with valsartan (51.4% AF recurrences in a 12-month follow-up) vs. the placebo group (52.1%, p = NS). Therefore, available data do not support the use of these drugs in secondary prevention of AF.
Giornale italiano di cardiologia (2006) 11/2010; 11(11):829-34.
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Serge Masson,
Aneta Aleksova,
Chiara Favero,
Lidia Staszewsky,
Marino Bernardinangeli,
Chiara Belvito,
Giovanni Cioffi,
Gianfranco Sinagra,
Carmine Mazzone,
Federico Bertocchi,
Tarcisio Vago,
Giuseppe Peri,
Ivan Cuccovillo,
Nobuhito Masuda,
Simona Barlera,
Alberto Mantovani,
Aldo P Maggioni,
Maria Grazia Franzosi, Marcello Disertori,
Roberto Latini
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ABSTRACT: Inflammation may play a significant role in the pathogenesis of atrial fibrillation (AF).
To examine the roles of three systemic inflammatory markers in predicting recurrent AF.
The association between the plasma concentrations of high-sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6) and pentraxin-3 (PTX3) with echocardiographic parameters and with the time to first recurrence of AF was tested in 382 patients with a history of AF but in sinus rhythm at randomisation, enrolled in the GISSI-AF biohumoral study.
Baseline PTX3 was related to left atrial, but not to left ventricular chamber volume. During one year of follow-up, 204 patients (53.1%) had a recurrent AF. There were no significant differences in baseline median [Q1-Q3] plasma concentrations of IL-6, hsCRP and PTX3 among patients with (2.11 [1.47-3.74] pg/ml, 3.30 [1.40-6.80] mg/l and 4.66 [3.27-6.97] ng/ml, respectively) or without recurrent AF (2.09 [1.37-2.90] pg/ml, p=0.182; 3.00 [1.10-6.20] mg/l, p=0.333; 5.09 [3.22-7.98] ng/ml, p=0.637). At 6 and 12 months follow-up, AF patients had significantly higher concentrations of IL-6 and PTX3 than those in sinus rhythm, and those with most recent episodes of AF had higher hsCRP. Baseline levels of IL-6, hsCRP or PTX3 were not significantly associated with a higher risk of recurrence of AF.
In patients with a history of AF, but without significant left ventricular dysfunction or heart failure, inflammatory biomarkers may be raised but are, at best, weak predictors of the risk for first recurrence of AF.
Heart (British Cardiac Society) 10/2010; 96(23):1909-14. · 4.22 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm (SR). Identifying risk factors for recurrence may help define the best strategy for secondary prevention.
The GISSI-AF trial enrolled 1,442 patients in SR with at least 2 documented AF episodes in the previous 6 months or after cardioversion in the last 2 weeks. Patients were randomized to valsartan or placebo; all other treatments for AF or underlying heart diseases were allowed. Primary end points were time to first recurrence of AF and proportion of patients with >1 AF episode during 1-year follow-up. We evaluated clinical and electrocardiographic baseline characteristics of all patients to identify independent predictors for AF recurrence using a Cox multivariable model.
Risk factors for AF recurrence were a history of 2 or more AF episodes in the previous 6 months, independent of the modality of SR restoration, spontaneous (HR 1.42, 95% CI 1.14-1.77, P = .002), or by cardioversion (HR 1.19, 95% CI 1.01-1.40, P = .038), and a lower heart rate during SR (HR 0.99, 95% CI 0.99-1.00, P = .052). The risk factors were the same for >1 AF recurrence. Patients treated with amiodarone had a lower risk for both end points (P < .0001 and P = .017), whereas those on diuretics had a greater risk (P = .009 and P = .003).
In the GISSI-AF study population, AF history had significant prognostic value independent of the modality of SR restoration. Amiodarone and diuretic treatment affected the rate of AF recurrence.
American heart journal 05/2010; 159(5):857-63. · 4.65 Impact Factor
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ABSTRACT: We report the first case in the literature of acute myocardial infarction due to very late (5 years) drug-eluting stent (DES) thrombosis presenting with inferior ST-elevation myocardial infarction immediately after epileptic convulsive seizures in a patient with known coronary artery disease. A bare-metal stent had been implanted in the left anterior descending coronary artery in 2002, and a drug-eluting stent implanted in the right coronary artery in 2003. We discuss the possible pathogenetic mechanisms implied in convulsive epileptic crisis resulting in development of very late DES thrombosis.
Journal of Thrombosis and Thrombolysis 09/2009; 29(4):512-5. · 1.48 Impact Factor
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ABSTRACT: We describe a case report of a patient affected by drug refractory persistent atrial fibrillation and dextrocardia, who underwent an ablation procedure using an electroanatomic mapping system.
Europace 09/2009; 11(10):1399-400. · 1.98 Impact Factor
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ABSTRACT: Atrial fibrillation is the most common cardiac arrhythmia, and no current therapy is ideal for control of this condition. Experimental studies suggest that angiotensin II-receptor blockers (ARBs) can influence atrial remodeling, and some clinical studies suggest that they may prevent atrial fibrillation.
We conducted a large, randomized, prospective, placebo-controlled, multicenter trial to test whether the ARB valsartan could reduce the recurrence of atrial fibrillation. We enrolled patients who were in sinus rhythm but had had either two or more documented episodes of atrial fibrillation in the previous 6 months or successful cardioversion for atrial fibrillation in the previous 2 weeks. To be eligible, patients also had to have underlying cardiovascular disease, diabetes, or left atrial enlargement. Patients were randomly assigned to receive valsartan or placebo. The two primary end points were the time to a first recurrence of atrial fibrillation and the proportion of patients who had more than one recurrence of atrial fibrillation over the course of 1 year.
A total of 1442 patients were enrolled in the study. Atrial fibrillation recurred in 371 of the 722 patients (51.4%) in the valsartan group, as compared with 375 of 720 (52.1%) in the placebo group (adjusted hazard ratio, 0.97; 96% confidence interval [CI], 0.83 to 1.14; P=0.73). More than one episode of atrial fibrillation occurred in 194 of 722 patients (26.9%) in the valsartan group and in 201 of 720 (27.9%) in the placebo group (adjusted odds ratio, 0.89; 99% CI, 0.64 to 1.23; P=0.34). The results were similar in all predefined subgroups of patients, including those who were not receiving angiotensin-converting-enzyme inhibitors.
Treatment with valsartan was not associated with a reduction in the incidence of recurrent atrial fibrillation. (ClinicalTrials.gov number, NCT00376272.)
New England Journal of Medicine 05/2009; 360(16):1606-17. · 53.30 Impact Factor
