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Biomedical subjects

Federico Lombardi

Publications and source records attributed to Federico Lombardi.

At least 19 recordsLinked to original sources
PubMed2006

Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial.

AIMS: Treatment of atrial fibrillation remains a major clinical challenge owing to the limited efficacy and safety of anti-arrhythmic drugs, particularly in patients with structural heart disease. METHODS AND RESULTS: To evaluate the efficacy of azimilide, a new class III anti-arrhythmic drug, we studied 658 patients with symptomatic persistent atrial fibrillation, adequate anticoagulant therapy, and planned electrical cardioversion. Patients were randomized to placebo, azimilide (125 mg o.d.), or sotalol (160 mg b.i.d.). Primary efficacy analysis was based on event recurrence, which was defined as atrial fibrillation lasting>24 h, or requiring DC cardioversion. Median time to recurrence was 14 days for azimilide, 12 days for placebo, and 28 days for sotalol (P=0.0320 when comparing azimilide with placebo; P=0.0002 when comparing azimilide with sotalol). The placebo-to-azimilide hazard ratio was 1.291 (95% CI: 1.022-1.629) and the sotalol-to-azimilide hazard ratio was 0.652 (95% CI: 0.523-0.814). Adverse events causing patient withdrawal were more frequent (P<0.01) in patients on azimilide (12.3%) and on sotalol (13.9%) than on placebo (5.4%). Eight patients in the sotalol (3.5%) and 16 in the azimilide (7.6%) group interrupted the study because of QTc prolongation. Torsade de pointes was reported in five patients of the azimilide group. The percentage of patients who completed the 26 week study period without events were 19% for azimilide, 15% for placebo, and 33% for sotalol (P<0.01). Unsuccessful day 4 cardioversion, arrhythmia recurrence, and adverse events were the main causes of withdrawal from the study. CONCLUSION: This study demonstrates that the anti-arrhythmic efficacy of azimilide is slightly superior to placebo but significantly inferior to sotalol in patients with persistent AF. The modest anti-arrhythmic efficacy and high rate of torsade de pointes and marked QTc prolongation limit azimilide utilization for the treatment of AF.

Adolescent↗
PubMed2006

Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease.

BACKGROUND: Autoimmunity and dysautonomia are established features of Chagas disease (ChD) that could be related to its pathogenesis. Our objective was to assess heart rate variability (HRV) and levels of anti-M2 receptors autoantibodies in ChD patients with and without left ventricular (LV) dysfunction, in order to establish if these abnormalities occur early and concomitantly in the course of the illness. METHODS: ChD patients (n=75) and healthy controls (n=14) underwent a standardized protocol including Doppler echocardiogram, Holter monitoring, HRV analysis, and measurement of anti-M2 receptors autoantibodies (ELISA). ChD patients were divided accordingly by the absence (group 1, n=45) or presence (group 2, n=30) of LV dysfunction, defined as reduced LV ejection fraction (<55%) or regional wall motion abnormalities (including ventricular aneurysm). RESULTS: Both ChD groups displayed increased optical density values of anti-M2 cholinergic autoantibodies (Median (IQR): control=1.98(0.51); ChD 1=2.76(0.97); ChD 2=2.72(1.34), p<.001) and reduced HF power of spectral analysis of HRV when compared to controls (Median (IQR) in ms2: control=1087(2284); ChD 1=286(763); ChD 2=285(763), p<.001). M2 levels were significantly correlated with HF power values (r=-0.32, p=0.023), but not with LV ejection fraction. CONCLUSIONS: Anti-muscarinic autoantibodies and abnormal vagal modulation occur early in ChD patients, independently of the presence of LV dysfunction. Levels of antibodies against M2 muscarinic receptors were significantly and negatively correlated with HRV index HF power, suggesting an inhibitory effect of autoantibodies in vagal function.

Adult↗
PubMed2006

Analysis of surface electrocardiograms in atrial fibrillation: techniques, research, and clinical applications.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy is sufficiently predictable by clinical and echocardiographic parameters. The purpose of this article is to describe technical aspects of novel electrocardiogram (ECG) analysis techniques and to present research and clinical applications of these methods for characterization of both the fibrillatory process and the ventricular response during AF. Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface ECG using digital signal processing (extraction of atrial signals and spectral analysis). This measurement shows large inter-individual variability and correlates well with intra-atrial cycle length, a parameter which appears to have primary importance in AF maintenance and response to therapy. AF with a low fibrillatory rate is more likely to terminate spontaneously and responds better to antiarrhythmic drugs or cardioversion, whereas high-rate AF is more often persistent and refractory to therapy. Ventricular responses during AF can be characterized by a variety of methods, which include analysis of heart rate variability, RR-interval histograms, Lorenz plots, and non-linear dynamics. These methods have all shown a certain degree of usefulness, either in scientific explorations of atrioventricular (AV) nodal function or in selected clinical questions such as predicting response to drugs, cardioversion, or AV nodal modification. The role of the autonomic nervous system for AF sustenance and termination, as well as for ventricular rate responses, can be explored by different ECG analysis methods. In conclusion, non-invasive characterization of atrial fibrillatory activity and ventricular response can be performed from the surface ECG in AF patients. Different signal processing techniques have been suggested for identification of underlying AF pathomechanisms and prediction of therapy efficacy.

Atrial Fibrillation↗
PubMed2006

Chronotropic incompetence and abnormal autonomic modulation in ambulatory Chagas disease patients.

BACKGROUND: Chagas disease (ChD) patients might present chronotropic incompetence during exercise, although its physiopathology remains uncertain. We evaluated the heart rate (HR) response to exercise testing in ChD patients in order to determine the role of autonomic modulation and left ventricular dysfunction in the physiopathology of chronotropic incompetence. METHODS: ChD ambulatory patients (n = 170) and healthy controls (n = 24) underwent a standardized protocol including Doppler echocardiography, Holter monitoring, HR variability analysis, brain natriuretic peptide (BNP) measurement, and maximal exercise testing. The chronotropic response was calculated as the percentage of predicted HR achieved and the HR increment (DeltaHR) during exercise. ChD patients were divided according to the absence or presence of cardiopathy and chronotropic incompetence (<85% predicted HR). RESULTS: Chronotropic incompetence was present in 34 (20%) of all ChD patients. The group with cardiopathy displayed reduced DeltaHR (91 +/- 19 bpm) during exercise in comparison with ChD patients without cardiopathy (100 +/- 19 bpm). Both the values observed in ChD groups were significantly different from those of controls (112 +/- 13 bpm). Exercise duration, maximal oxygen consumption, and systolic blood pressure increment were significantly reduced in patients with abnormal chronotropic response. DeltaHR during the exercise was significantly correlated with markers of autonomic control of sinus node, such as rest HR (r =-0.498, P <or= 0.001), peak HR during exercise (r = 0.775, P <or= 0.001), minimal HR during Holter recording (r =-0.231, P = 0.003), and high- and low-frequency components of short-term HR variability (r = 0.188, P = 0.042 and r = 0.203, P = 0.027). Neither left ventricular function nor BNP levels were independently related to the presence of chronotropic incompetence. CONCLUSIONS: Chronotropic incompetence may be considered an early sign of autonomic dysfunction in ChD patients.

Adult↗
PubMed2006

Abnormalities in fractal heart rate dynamics in Chagas disease.

BACKGROUND AND METHODS: In order to study fractal HR dynamics in Chagas disease, we performed detrended fluctuation analysis (DFA)-along with analysis of power-law beta slope (beta index) and standard deviation of N-N intervals (SDNN)-in edited and unedited (with ventricular premature beats - VPBs, only in DFA analysis) series of R-R intervals from Holter monitoring of healthy controls (Group 0, n = 27) and Chagas disease patients with left ventricular (LV) ejection fraction >50% (Group 1, n = 137) and with LV ejection fraction <50% (Group 2, n = 23). RESULTS: When analyzed from the edited R-R interval data, the long-term scaling exponent alpha(2) is altered both among the Chagas patients with and without LV dysfunction. The short-term scaling exponent alpha(1) was higher in Group 1 Chagas patients as compared to controls (P < 0.01) and did not differ between Group 2 and controls. In unedited R-R interval series, alpha(1) was significantly reduced in Group 2 Chagas patients (0.55 +/- 0.002) as compared to controls (0.90 +/- 0.002) and Group 1 (0.91 +/- 0.003) (P < 0.001), but did not differ between Group 1 and controls. Similarly alpha(2) was lower in Group 2 compared to other groups (P < 0.001). SDNN did not differ between the groups, but the beta index derived from 1/f model was reduced both in Group 1 and 2 Chagas patients as compared to controls (P < 0.01). There was strong correlation (rs = 0.82; P < 0.001) between the beta and alpha(2) index from edited series. There was an inverse correlation (rs =-0.63, P < 0.01) between the number of VPBs and alpha(1) index of unedited series. CONCLUSIONS: The long-term fractal HR dynamics altered in chagasic patients with and without LV dysfunction could be an early sign of autonomic dysfunction. Patients with impaired LV function show marked alterations in short-term fractal HR dynamics toward more random behavior, mainly due to frequent ectopy. Prospective studies are necessary to define the value of these indices as predictors of death in Chagas disease.

Adult↗
PubMed2006

Assessment of spatial organization in the atria during paroxysmal atrial fibrillation and adrenergic stimulation.

Non-linear parameters were computed to assess the extent of spatial organization in the atria in terms of coupling/synchronization between electrograms recorded in different atrial sites. Recordings of 9 patients suffering from paroxysmal atrial fibrillation were tested during four clinical experimental conditions: sinus rhythm and atrial fibrillation, both before and after isoproterenol infusion, a drug mimicking adrenergic activation. Two non-linear metrics were investigated: an index of non-linear association (NLA) and a synchronization (S) index based on the cross-conditional entropy. Results evidence the presence of reduced coupling after drug infusion in both sinus rhythm and atrial fibrillation. Moreover, passing from the NLA to the S index, the capability of the parameter to capture the subtle changes due to isoproterenol administration increased.

Adrenergic beta-Agonists↗
PubMed2006

Pharmacological treatment of atrial fibrillation: mechanisms of action and efficacy of class III drugs.

Atrial fibrillation represents a major clinical, social and economical matter, and its importance is expected to increase even more in the near future. The progressive ageing of population is associated with an inevitable rising in incidence and prevalence of this rhythm disorder, which limits functional capability, favours occurrence of cerebrovascular events and increases people's request for emergency room visits and hospital recovery. In spite of the increasing successes of the interventional non-pharmacological therapies, drug treatment of patients with atrial fibrillation in relation to conversion to sinus rhythm and prevention of recurrences, maintains a critical role. Several antiarrhythmic drugs are nowadays available, but their efficacy is limited by the high rate of arrhythmias recurrences and by side effects during acute and chronic treatment. Drugs interfering with potassium channels (Class III drugs) have been proposed and used in patients with atrial fibrillation. Aim of this review is to discuss the most recent data on the efficacy and feasibility of class III drugs in atrial fibrillation. Experimental and clinical data on dronedarone, ibutilide, dofetilide, azimilide, ersentilide and ambasilide will be hereby discussed.

Anti-Arrhythmia Agents↗
PubMed2005

[Chronotropic-metabolic index in Chagas' disease].

Chronotropic incompetence is a common feature in Chagas' disease patients. New methodologies are now available to evaluate the chronotropic response in different subsets. The chronotropic-metabolic index (CMI) is one of these new indexes and quantifies the relationship between the increment of heart rate and the maximal oxygen consumption (VO2 max) during exercise testing. In normal subjects there is linear response and the index is round 1.0. The aim of the study was to evaluate the chronotropic response in healthy controls and Chagas' disease patients with and without left ventricular dysfunction, using CMI. Twenty-four controls and 171 Chagas' disease patients underwent a clinical protocol and maximal exercise testing. Chagas' disease patients were divided into two groups: Ch1= patients with ejection fraction (EF) > 39% and Ch2 = EF < 40%. CMI was analyzed and calculated according to the Wilkoff method. Chagas' disease patients were older than controls and showed higher prevalence of right bundle branch block, as well as lower VO2 max during exercise. Both groups of Chagas' disease patients showed a less steep curve in the chronotropic-metabolic index (Ch1: 0.91+/-0.10, Ch2: 0.89+/-0.08) than controls (1.0+/-0.12, p < 0.001). Chagas' disease patients with and without left ventricular dysfunction chronotropic incompetence may exhibit reduced chronotropic response to exercise, expressed by a less steep chronotropic-metabolic index.

Adult↗
PubMed2005

Prognostic value of C-reactive protein in patients with stress induced myocardial ischemia.

OBJECTIVE: Inflammation plays a critical role in the pathogenesis of atherosclerosis. Possible association between C-reactive protein (CRP), stress-induced myocardial ischemia and clinical outcome was investigated. DESIGN, PATIENTS AND RESULTS: We correlated scintigraphic scan and CRP values of 101 consecutive out-patients who performed an exercise stress test for evaluation of chest pain (n=49) or scheduled control after myocardial infarction (n=52). CRP levels were determined before and after exercise. Twenty-three patients had reversible defects and presented CRP levels [mean (S.D.) 5.6 (3.3) mg/l] greater than subjects with fixed [mean (S.D.) 4.6 (4.5) mg/l] or no [mean (S.D.) 2.8 (2.9) mg/l] defects. Odds ratio for the association between high (3rd, tertile, >4.7 mg/l) CRP levels and reversible defects was 5.6 (95% CI 1.6 to 20; p=0.009). During a follow-up of 2.3 (0.7) years, 18 patients reached a clinical end-point consisting in one Q-wave myocardial infarction, eight non-Q-wave myocardial infarction or unstable angina and nine percutaneous coronary interventions. When the impact of different risk factors on the development of clinical endpoint was evaluated, the hazard ratio associated with high CRP levels was 11.0 (95% CI 3.0 to 41; p<0.001). CONCLUSIONS: These findings suggest that in ambulatory patients, high CRP levels may predict exercise-induced ischemia and patient outcome.

Aged↗
PubMed2005

Utility of implantable loop recorder (Reveal Plus) in the diagnosis of unexplained syncope.

AIMS: In about 30% of patients with syncope, the responsible mechanisms remain unrecognised. Nevertheless, the possibility of an arrhythmic aetiology remains, however, difficult to rule out. METHODS: We therefore monitored with an implantable loop recorder (ILR, Reveal Plus, Medtronic) 34 subjects (60+/-15 years) with at least two unexplained syncopal episodes and negative neurological and cardiovascular work-up. RESULTS: During a follow-up of 7+/-4 months, syncope occurred in 11 subjects. In nine of them the mechanisms responsible for these events were identified by ILR monitoring: marked bradycardia or asystole (n=6), atrial fibrillation with wide QRS tachycardia (n=1) and sinus rhythm with fine artifacts likely to be due to muscle contractions (n=2). Pre-syncope occurred in seven patients: advanced atrioventricular block (n=3), sinus tachycardia (n=1), and wide QRS tachycardia (n=1) were documented. Thus, when considering all 18 patients with recurrences, a diagnosis was achieved in 53% of subjects. Recognition of the rhythm disorder in seven patients with syncope and four patients with pre-syncope guided patient management. CONCLUSIONS: These data indicate that ILR monitoring facilitates the identification of mechanisms responsible for recurrences and therapeutic management in subjects with syncope or pre-syncope and negative traditional neurological and cardiovascular work-up.

Adult↗
PubMed2005

Heart rate turbulence and left ventricular ejection fraction in Chagas disease.

AIMS: Chagas disease patients often present premature ventricular complexes (PVCs), depression of left ventricular ejection fraction (LVEF) and autonomic dysfunction, which is generally evaluated by heart rate variability (HRV) analysis. As frequent PVCs may complicate HRV computation, we measured heart rate turbulence (HRT) and evaluated the correlation between ejection fraction and HRT or HRV in Chagas disease. METHODS: We studied 30 patients (47+/-11 years, 20 men) with Chagas cardiomyopathy and left ventricular dilatation who underwent clinical evaluation, ejection fraction (EF: 45+/-14%) determination and 24-h Holter monitoring (median PVC=1781). In all patients, the standard deviation of normal RR intervals (SDNN), the square root of the mean square differences of successive RR intervals (RMSSD) and values of turbulence onset (TO) and turbulence slope (TS) were calculated. RESULTS: HRT indices were independent of mean RR interval and presented high correlation with EF: TO (-0.11+/-0.01%, r=-0.60, P<0.001) and TS (5.8+/-3.7 ms/RR-interval, r=0.73, P<0.001). Of HRV parameters, only SDNN, corrected for mean RR interval, showed a weak but not significant correlation with EF (r=0.41). The comparison of HRT/EF and HRV/EF correlation coefficients, indicated the presence of a significant difference (P=0.017). CONCLUSIONS: HRT indices appear to correlate better with EF than SDNN in Chagas disease. Thus, an analysis based on heart rate transient adaptation seems to perform better than HRV in detecting the autonomic alterations that parallel left ventricular dysfunction in Chagas disease patients. The high number of PVCs observed in these patients further support the use of HRT methodology.

Adult↗
PubMed2005

Renin-angiotensin system block and atrial fibrillation.

Atrial fibrillation is the most common disorder of cardiac rhythm. In spite of diagnosis simplicity, patients with atrial fibrillation are difficult to treat. In the recent years with the description of the phenomenon called remodelling, it has been possible to better define the principle mechanisms responsible for initiation, maintenance and, in some instances, termination of atrial fibrillation. Electrical, mechanical and anatomical remodelling indicate those alterations that, once established, may vanish any attempt to restore sinus rhythm. Atrial fibrosis is probably the most critical component of the remodelling process and appears to be largely mediated by the activation of the Renin-Angiotensin-Aldosterone System. Both experimental and clinical data have confirmed the pro-arrhythmic role of the Renin-Angiotensin-Aldosterone System and demonstrated an anti-arrhythmic effects of ACE-inhibitors and AT(1) receptor blockers. Regarding atrial fibrillation, it has been recently reported that the adjunction of AT(1) receptor blocker to amiodarone was more effective than the anti-arrhythmic drug alone, in reducing arrhythmia recurrence after electrical cardioversion. This and subsequent clinical observations indicate that pharmacological interventions capable of interfering with the electrical and structural remodelling process are of critical importance in the management of patients with atrial fibrillation. ACE inhibitors and AT(1) receptor blockers represent new and efficient therapeutical options to contrast the nearly inevitable progression of this arrhythmia towards its permanent form.

Aldosterone↗
PubMed2004

Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration.

BACKGROUND: The autonomic nervous system (ANS) plays an important role in the genesis and maintenance of atrial fibrillation (AF), but quantification of its electrophysiologic effects is extremely complex and difficult. Aim of the study was to evaluate the capability of linear and non-linear indexes to capture the fine changing dynamics of atrial signals and local atrial period (LAP) series during adrenergic activation induced by isoproterenol (a sympathomimetic drug) infusion. METHODS: Nine patients with paroxysmal or persistent AF (aged 60 +/- 6) underwent electrophysiological study in which isoproterenol was administered to patients. Atrial electrograms were acquired during i) sinus rhythm (SR); ii) sinus rhythm during isoproterenol (SRISO) administration; iii) atrial fibrillation (AF) and iv) atrial fibrillation during isoproterenol (AFISO) administration. The level of organization between two electrograms was assessed by the synchronization index (S), whereas the degree of recurrence of a pattern in a signal was defined by the regularity index (R). In addition, the level of predictability (LP) and regularity of LAP series were computed. RESULTS: LAP series analysis shows a reduction of both LP and R index during isoproterenol infusion in SR and AF (RSR = 0.75 +/- 0.07 RSRISO = 0.69 +/- 0.10, p < 0.0001; RAF = 0.31 +/- 0.08 RAFISO = 0.26 +/- 0.09, p < 0.0001; LPSR = 99.99 +/- 0.001 LPSRISO = 99.97 +/- 0.03, p < 0.0001; LPAF = 69.46 +/- 21.55 LPAFISO = 55 +/- 24.75; p < 0.0001). Electrograms analysis shows R index reductions both in SR (RSR = 0.49 +/- 0.08 RSRISO = 0.46 +/- 0.09 p < 0.0001) and in AF (RAF = 0.29 +/- 0.09 RAFISO = 0.28 +/- 0.08 n.s.). CONCLUSIONS: The proposed parameters succeeded in discriminating the subtle changes due to isoproterenol infusion during both the rhythms especially when considering LAP series analysis. The reduced value of analyzed parameters after isoproterenol administration could reflect an important pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF.

Atrial Fibrillation↗
PubMed2004

Autonomic nervous system and paroxysmal atrial fibrillation: a study based on the analysis of RR interval changes before, during and after paroxysmal atrial fibrillation.

AIMS: To evaluate the presence of an abnormal autonomic modulation before, during and immediately after paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: We analysed Holter recordings of 65 patients with 110 PAF episodes lasting more then 30 s. Mean RR interval, co-efficient of variation and short-term heart rate variability were measured before, during and after PAF episodes. We observed a significant correlation between the coupling interval and both the cycle length measured from 30 min up to few cycles before PAF onset, and ventricular response. When comparing the heart rate variability (HRV) before and after PAF we observed a significant reduction of the low frequency/high frequency components (LF/HF) ratio (from 6.2+/-7.4 to 3.2+/-4.1). A short-long-short cycle sequence was detectable in 37 PAF onsets associated with a greater incidence of atrial ectopic beats and a greater LF component (62+/-25 vs. 53+/-27 normalised units) in comparison to the remaining episodes. When onsets were divided for a LF/HF ratio cut-off value of > or = 2 to separate episodes with a predominant sympathetic, as opposed to those with a prevailing vagal (LF/HF<2) modulation, we observed opposite changes (from 9.1+/-7.8 to 4+/-3.7 and from 0.8+/-0.5 to 2+/-3.6, respectively) consistent with a recovery of a more physiological sympatho-vagal balance immediately after recovery of sinus rhythm. No changes in co-efficient of variation of ventricular response were detectable before PAF termination. CONCLUSIONS: A predominant sympathetic modulation characterises the majority of PAF onsets whereas a vagal predominance was detectable in about 30% of episodes. These patterns are no longer detectable after recovery of sinus rhythm.

Aged↗
PubMed2004

Cardiac autonomic modulation in normal, high-risk, and in vitro fertilization pregnancies during the first trimester.

OBJECTIVES: The purpose of this study was to test the adaptation of autonomic modulation of heart rate in high-risk or in vitro fertilization (IVF) pregnancies during the first trimester. STUDY DESIGN: Thirty-three pregnant women were studied between 6.0 and 12.5 weeks of gestation and were divided into three groups: normal (n=17), high-risk (n=7), and IVF pregnancies (n=9), together with 9 nonpregnant women of comparable age. All subjects underwent a short-term continuous electrocardiographic recording to measure short-term heart rate variability (HRV). RESULTS: Average values of mean R-R interval, total power, and low-frequency (LF) component were similar in nonpregnant and normally pregnant women. The high-frequency (HF) component was only slightly increased in normal pregnant women but no difference was observed in LF/HF ratio. High-risk and IVF pregnancies were characterized by a significant increase in LF component in comparison to normal pregnancies. In pregnancies that had obstetric complications, signs of abnormal autonomic modulation of the sinus node were particularly evident. CONCLUSION: Short-term analysis of HRV in high-risk and IVF pregnancies was significantly different from that observed in normal pregnancies. These differences were more significant in those pregnancies later complicated by an adverse outcome, suggesting an early origin of these pathologic conditions.

Adult↗