PubMed Health⌕ Search

Biomedical subjects

Mauro Biffi

Publications and source records attributed to Mauro Biffi.

At least 19 recordsLinked to original sources
PubMed2006

VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that regulates bone metabolism, controls calcium homeostasis, and possesses immunomodulatory properties. We show here that 1,25(OH)2D3 contributes to the regulation of development and function of mast cells, which play a critical role in several inflammatory disorders. 1,25(OH)2D3 promotes apoptosis and inhibits maturation of mouse bone marrow-derived mast cell precursors. Dose-dependent inhibition of mast cell differentiation by 1,25(OH)2D3 is observed at discrete, intermediate stages of mast cell development, identified by expression of c-kit, FcepsilonRI, and IL-3 receptor-alpha chain, and depends on the expression of the vitamin D receptor (VDR). It is important that mast cell progenitors obtained from VDR-ablated mice undergo an accelerated maturation in vitro and give rise to more responsive mast cells than wild-type. Furthermore, histological analysis of mast cell density in peripheral tissues reveals a moderate increase in the number of mast cells in the skin of VDR-deficient mice compared with wild-type animals. These data support the hypothesis of a physiological role of 1,25(OH)2D3 in mast cell development and suggest novel, therapeutic uses of 1,25(OH)2D3 analogs.

Animals↗
PubMed2006

Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response.

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or = 150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration < or = 150 pg/ml might be a clinically useful predictor of medium-term response to CRT.

Aged↗
PubMed2006

Role of ventricular Autocapture function in increasing longevity of DDDR pacemakers: a prospective study.

AIMS: Autocapture is an algorithm for automatic adaptation of ventricular output to capture threshold. The aim of this prospective study was to estimate the effects of ventricular Autocapture algorithm on DDD-DDDR pacemaker longevity. METHODS AND RESULTS: Eighty-three patients implanted with a DDD-DDDR pacemaker (Affinity or Entity; St Jude Medical, USA) were enrolled and the Autocapture function was activated pre-discharge. Ventricular pulse duration was randomly programmed at 0.3 or 0.4 ms, with a cross-over at 8-12 weeks and again at 13-14 months. Diagnostic data were retrieved from device memory and by calculating battery current drain from long-term threshold recordings; device longevity was estimated at the following settings: Autocapture with a pulse duration of 0.3 and 0.4 ms, respectively, standard output (3.5 V, 0.4 ms) and conventional low output programming (2.5 V, 0.4 ms). According to a series of assumptions, Autocapture was associated with a 55-60% increase in estimated device longevity compared with standard output programming and a 6-7% increase in longevity compared with low output programming. No significant differences were found between Autocapture programmed with a pulse duration of 0.3 or 0.4 ms. In projections to a 10-year follow-up, use of the Autocapture function resulted in a 42% reduction in pacing-related estimated costs compared with standard output programming at 3.5 V, 0.4 ms. CONCLUSION: Pacing with constant adaptation of ventricular output in dual-chamber devices has the potential to increase generator longevity and to reduce sizeably pacing-related costs compared with standard programming.

Adult↗
PubMed2006

Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. The Resynchronization for the HemodYnamic Treatment for Heart Failure Management II implantable cardioverter defibrillator (RHYTHM II ICD) study.

BACKGROUND: The clinical value of interventricular (V-V) delay optimization in patients with chronic congestive heart failure (CHF) undergoing implantation of a device for cardiac resynchronization therapy (CRT) has not been clearly demonstrated. METHODS: RHYTHM II was a single-blind randomized trial including 121 recipients of a device for CRT with cardioverter/defibrillator capabilities (CRT-D) randomly assigned in a 1:3 ratio to simultaneous (n = 30) versus optimized (OPT) (n = 91) biventricular pacing. V-V delay was optimized by echocardiography. The study end points were (1) freedom from CRT-D system-related complications and (2) changes between preimplant and 6 months of follow-up in (a) New York Heart Association CHF functional class, (b) distance covered during a 6-minute hall walk, and (c) quality of life (QOL). RESULTS: In the OPT group, the V-V delay ranged from 0 to 80 milliseconds, with 28.4% of patients stimulated at an OPT V-V delay of 0 milliseconds. The overall 6-month survival free of adverse events requiring invasive interventions was 81.8%. In the whole cohort, 6 months of CRT-D was associated with a significant decrease in New York Heart Association class, increase in the distance covered during the 6-minute hall walk, and improvement in QOL (each P < .0001). The effects of CRT-D on these end points were similar in both study groups. CONCLUSIONS: Cardioverter-defibrillator capabilities was associated with a significant alleviation of CHF symptoms, increase in functional capacity, and improvement in QOL. The optimization of the V-V delay conferred no additional benefit compared with simultaneous biventricular stimulation.

Aged↗
PubMed2006

Characteristics of ventricular tachyarrhythmias occurring in ischemic versus nonischemic patients implanted with a biventricular cardioverter-defibrillator for primary or secondary prevention of sudden death.

OBJECTIVES: The InSync ICD Registry evaluated patients indicated for cardiac resynchronization therapy with defibrillation. BACKGROUND: Cardiac resynchronization therapy with defibrillation systems are prescribed for both primary and secondary prevention of sudden cardiac death in patients with heart failure with both ischemic and nonischemic etiology. The characterization of ventricular tachyarrhythmias detected by the ICD is not well known in these subpopulations. METHODS: We enrolled 421 patients with symptomatic heart failure despite optimized medical treatment, ventricular dyssynchrony, and primary or secondary ICD indications. An electrophysiologist reviewed all spontaneous episodes. Patients were grouped by etiology and ICD indications. RESULTS: The 421 patients included 292 ischemic (159 primary prevention) and 129 nonischemic (68 primary prevention) patients. In 19 +/- 11 months of follow-up, 110 patients (63 ischemic, 30 primary prevention and 47 nonischemic, 21 primary prevention) presented ventricular tachyarrhythmias, occurring in a ventricular tachycardia (VT) or a ventricular fibrillation zone (1382 and 456 events, respectively). The incidence of overall ventricular tachyarrhythmias in nonischemic patients in secondary prevention (35.7% at 1 year) was higher than in ischemic patients implanted for either indication (16.5% and 22.9% at 1 year, respectively). The incidence of self-terminating ventricular tachyarrhythmias was greater in patients with nonischemic heart disease, regardless of indication. Patients with ischemic heart disease in primary prevention had a lower occurrence of VTs, whereas nonischemic patients in primary prevention had faster VTs. CONCLUSIONS: Both rate of occurrence and characteristics of detected ventricular tachyarrhythmias vary according to underlying etiology and indication. Therefore, different device programming according to patient's profile is advisable to improve ventricular tachyarrhythmias management.

Adult↗
PubMed2006

Primary prevention of sudden cardiac death: can we afford the cost of cardioverter-defibrillators? Data from the Search-MI Registry-Italian sub-study.

BACKGROUND: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2-5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5-7 years--a particularly interesting subject for further registry studies. METHODS AND RESULTS: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5-7 year time horizon, the average daily cost was estimated to be euro 4.60-euro 6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90-$11.40. CONCLUSIONS: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.

Aged↗
PubMed2005

Heart failure after myocardial revascularization: risk markers.

We investigated the prognostic weight of several risk factors for heart failure in patients undergoing CABG. We followed 351 consecutive patients for 18+/-12 months after surgery to assess clinical outcome, presence and degree of heart failure. The risk of developing heart failure >class 2 at 1 year was investigated by logistic regression on the following preoperative variables: sex, age, left ventricular EF, QRS duration, previous MI, history of heart failure, atrial fibrillation (AF), hypertension, hypercholesterolemia, diabetes, previous stroke. Age was 70+/-8 years and EF was 54+/-12% at the time of surgery. Heart failure >class 2 occurred in 95/351 patients (27%) at follow up. Logistic regression identified QRS duration (OR=1.02), a history of stroke (OR=3.94), and diabetes (OR=1.98) as predictors of CHF at follow up. All the other variables were not risk markers for heart failure at logistic regression. Thirty five patients (10%) had QRS> or =140 ms before surgery; 51% of them had CHF at follow up compared to 24% of patients with QRS<140 ms (p<0.05). In the current surgical era, candidates to CABG (50% of patients older than 70 years) have a relevant likelihood of heart failure at follow up, despite myocardial revascularization. Risk stratification may rely upon inexpensive variables as previous stroke, diabetes, and QRS duration. A minority of patients (5%) could benefit from LV-based pacing, which should be considered at the same surgical time via an epicardial implantation.

Adult↗
PubMed2005

Acute and chronic haemodynamic effects of biventricular pacing and of switching to different pacing modalities in heart failure patients.

BACKGROUND: In patients with severe heart failure, sinus rhythm and wide QRS complex biventricular (BiV) pacing leads to clinical and haemodynamic improvement, but the immediate reversibility of these changes is not known. METHODS: We assessed the acute and medium-term (3-month) haemodynamic effects of BiV pacing and of switching to other pacing modalities in 21 patients with severe heart failure, sinus rhythm and QRS>or=130 ms. Haemodynamic studies were performed: 1) at the time of implantation of a BiV pacing device, during AAI pacing, atrial synchronous right ventricular (RV) pacing, atrial synchronous left ventricular (LV) pacing and atrial synchronous BiV pacing (all at 100 bpm); 2) after 3 months of continuous BiV pacing--with evaluations being made by switching to RV and the other pacing modalities. RESULTS: At both the acute and medium-term evaluations, BiV pacing provided the greatest improvement in cardiac index. Switching from BiV to RV pacing led to a more marked decrease in the cardiac index at 3 months. No strict correlation was evident between acute and medium-term effects of BiV pacing on cardiac index. CONCLUSION: Cardiac resynchronization by BiV pacing provides acute/medium-term improvements in cardiac index. Sudden, medium-term failure of LV stimulation can lead to an even more pronounced haemodynamic derangement than that inducible by RV pacing at baseline. Acute haemodynamic evaluations do not seem to provide a powerful way for identifying medium-term responders.

Acute Disease↗
PubMed2005

A controlled study on the effect of verapamil on atrial tachycaarrhythmias in patients with brady-tachy syndrome implanted with a DDDR pacemaker.

While verapamil has been proposed as a treatment for reducing electrophysiological remodeling due to atrial fibrillation and atrial tachyarrhythmias, no previous study has tested its effects in brady-tachy patients implanted with a dual-chamber pacemaker. Fourteen patients with frequent episodes of atrial fibrillation (> or =2 episodes/month) in the setting of brady-tachy syndrome, implanted with a DDDR pacing system with extensive monitor function (Selection 900, Vitatron) were enrolled. Four months after implantation, they were randomly allocated to a 2-month period of treatment with verapamil (240 mg/day) or to no treatment, followed by a crossover. The burden of atrial tachyarrhythmias, the total number of hours spent in atrial tachyarrhythmia and the mean number of hours per day spent in atrial tachyarrhythmia were retrieved from diagnostic devices. The accuracy of atrial tachyarrhythmias detection was confirmed independently by two observers. The main results showed that treatment with verapamil was associated with a trend towards an higher percentage of atrial pacing in comparison with control (mean value+/-S.D.=63.2+/-29.9% vs. 57.3+/-30.6%, median value 53% vs. 49%, P value at Wilcoxon signed rank test=0.069), but without any significant reduction in atrial tachyarrhythmia burden (4.5+/-11.8 vs. 3.3+/-9.1%) or total hours spent in atrial tachyarrhythmia (65+/-161 vs. 48+/-131 h). Palpitation episodes were not significantly reduced by verapamil treatment in comparison with control (10.3+/-7.8 vs. 6.1+/-6.5). In conclusion, verapamil does not exert any beneficial effect on documented episodes of atrial tachyarrhythmia in patients with brady-tachy syndrome implanted with a DDDR device. Moreover, this drug was ineffective in reducing the number of palpitation episodes reported by the patient.

Aged↗
PubMed2005

P wave dispersion and short-term vs. late atrial fibrillation recurrences after cardioversion.

BACKGROUND: P wave dispersion has been previously suggested as a potential tool for predicting the risk of recurrence of atrial fibrillation after electrical cardioversion. We investigated whether different P wave dispersion values are associated with recurrence of atrial fibrillation in the short (< or =1 month after cardioversion) and longer term. METHODS: In 37 patients with long-lasting persistent atrial fibrillation (mean duration 21 +/- 36 months) with (n = 19) or without (n = 18) amiodarone pretreatment as antiarrhythmic prophylaxis, maximum and minimum P wave duration and P wave dispersion were measured 1 min after internal cardioversion. RESULTS: P wave dispersion was lower in patients with amiodarone pretreatment (28.3 +/- 9.5 vs. 21.9 +/- 7.3 ms, P = 0.029). The subgroups of patients with recurrence of atrial fibrillation at 1 month or in the long-term did not differ from the rest of the study sample regarding age, sex, atrial fibrillation duration, left atrial dimensions or ejection fraction. P wave dispersion was significantly higher in patients with short-term atrial fibrillation recurrence (< or = 1 month) than in the rest of the population. Furthermore, P wave dispersion values >25 ms were associated with a higher short-term relapse rate. No significant relation was present in the long-term. CONCLUSIONS: Our results suggest that P wave dispersion analysis immediately after internal cardioversion may help predict short-term recurrences of atrial fibrillation. These findings may be related to different mechanisms and predisposing factors for short-term and late recurrences. The long-term predictive value of serial evaluations of P wave dispersion during follow-up deserves investigation.

Aged↗
PubMed2005

Electrocardiographic remodeling during cardiac resynchronization therapy.

BACKGROUND: More information is required on the relationship between electrical and structural reverse remodeling in patients treated with cardiac resynchronization therapy. METHODS: QRS and JT intervals were investigated during different pacing modes before and 3 months after implantation of a device for biventricular (BiV) pacing in 20 patients with severe drug-refractory heart failure (with left ventricular ejection fraction < 40% and QRS > 120 ms); structural remodeling was evaluated by echocardiography. RESULTS: QRS interval was significantly shortened by BiV pacing both acutely (p=0.002) and at 3 months (p=0.007). No significant change was found in the JT interval. The extent of QRS shortening obtained by BiV pacing showed moderate correlations with the reduction of end-systolic and end-diastolic volumes (r=0.53, p=0.016 and r=0.45, p=0.045, respectively) as well as with increase of left ventricular ejection fraction (r=0.49, p=0.028) at 3 months. The widening of QRS observed during right ventricular (RV) pacing was greater after 3 months of BiV pacing (with respect to acute assessments), suggesting accentuation of pacing-induced electrical dyssynchrony after a period of pacing-induced resynchronization. CONCLUSION: The extent of QRS shortening induced by BiV pacing appears to correlate with the reverse structural remodeling (in terms of reduction in end-systolic volume). The acute changes and the remodeling process occurring at mid-term in the overall population of CRT-treated patients do not appear to involve the JT interval. A period of pacing-induced resynchronization appears to accentuate the potential for RV pacing-driven electrical dyssynchrony.

Adult↗
PubMed2005

Implantable dual-chamber defibrillator for the selective treatment of spontaneous atrial and ventricular arrhythmias: arrhythmia incidence and device performance.

INTRODUCTION: Atrial tachyarrhythmias are a common co-morbidity in patients with an ICD indication. Recently introduced ICD's are equipped to independently detect and treat atrial and ventricular tachyarrhythmias. The purpose of this prospective study was to evaluate the incidence and termination of spontaneous atrial and ventricular tachyarrythmias in patients with a history of atrial tachyarrhythmias. METHODS AND RESULTS: Ninety patients, 70% male with an ICD indication and history of atrial tachyarrhythmia (LVEF 45 +/- 6%, [AT/AF indication 55 +/- 10, AT/VT 45 +/- 16], 46% CAD) were enrolled and 89 were implanted with a VENTAK PRIZM AVT (Guidant). Spontaneous atrial and ventricular tachyarrhythmias were printed and evaluated during an average follow-up period of 272 +/- 72 days utilizing the stored intracardial electrogram function of the device. Nineteen patients (21%) presented had only atrial tachyarrhythmias, 32 patients (36%) had both atrial and ventricular tachyarrhythmias and 18 patients (20%) had only ventricular tachyarrhythmias. Patients with only atrial tachyarrhythmias had a total of 3274 atrial episodes; 2002 terminated spontaneously, 1264 were treated with ATP and 8 with shock therapy. ATP was successful in 735 (58%) of 1264 episodes. Patients with both atrial and ventricular tachyarrhythmias had 7277 documented atrial tachyarrhythmias, 5231 terminated spontaneously, 1153 of 2009 were terminated by ATP (57.4%) and 37 by shock therapy (20 patient controlled). Atrial tachyarrhythmias identified as atrial flutter (AT) by the atrial rhythm classification (ARC) algorithm had a higher ATP conversion success rate than episodes identified as atrial fibrillation (AF); 66.7% for AT and 26.4% for AF. Patients with only ventricular tachyarrhythmias had 690 documented episodes, 401 terminated spontaneously, 248 (85.8%) were terminated by ATP and 41 by shock. CONCLUSION: Seventy-seven percent of patients with an ICD indication had spontaneous atrial and/or ventricular tachyharrhythmias within the first 6 months after ICD implantation. ATP therapy terminated 58% of all atrial tachyarrhytmias and 66.7% of the atrial flutters. The dual chamber ICD detected, classified and terminated all ventricular tacharrhythmias appropriately.

Aged↗
PubMed2005

Pacing with capture verification in candidates for resynchronisation therapy: a feasibility study.

BACKGROUND: Devices for cardiac resynchronisation therapy (CRT) deliver energy into 3 output channels. Such a burden can significantly reduce device longevity. Autocapture has been shown to improve pacemaker longevity and safety of right ventricular pacing in clinical studies. The aim of this study was to investigate the application of Autocapture during biventricular pacing (BIV) to decrease the energy cost of CRT. METHODS: During implantation of BIV devices, an acute study was performed to test the hypothesis that the evoked response (ER) elicited by each delivered stimulus is correctly detected and measured either on the right ventricular (RV) channel during BIV pacing with the left ventricular (LV) channel pacing first, or in the LV channel with the RV channel pacing first. A reliable measurement of ER is the critical requirement for the correct performance of Autocapture. RESULTS: ER amplitude in the right ventricle during BIV pacing was not significantly decreased compared with RV pacing in the VVI mode (16.36+/-5.27 mV vs 17.09+/-6.12 mV). ER amplitude in the left ventricle during BIV pacing was not significantly decreased compared with LV pacing in the VVI mode (12.4+/-8.95 mV vs 12.25+/-8.97 mV). Three patients in atrial fibrillation had a DDDR pacemaker with the LV lead connected to the atrial port, and received BIV pacing with Autocapture turned on in the RV channel. Autocapture performance in the long term, as assessed by the trend of RV threshold over 20+/-8 months, showed that LV depolarisation was never sensed as an ER on the RV channel. CONCLUSIONS: Our observations support the feasibility and safety of capture verification during BIV pacing on the ventricular channel paced secondly, which could increase the longevity of CRT devices, and decrease the costs of this new therapy for heart failure patients.

Algorithms↗
PubMed2005

Mechanisms of pain associated with internal defibrillation shocks: results of a randomized study of shock waveform.

BACKGROUND: Shock pain has limited the acceptance of the implantable atrial cardioverter and is a complication of ventricular implantable cardioverter-defibrillator therapy. Rounding off of the peak of a shock waveform reduces pain. Whether the pain reduction results from reduction in the peak voltage or from the rounding has not been established. In other words, does reducing the extreme dV/dt (voltage derivative) of the conventional truncated exponential capacitive discharge waveform reduce pain? OBJECTIVES: The purpose of this study was to compare the relative contributions of peak voltage and waveform shape to pain. METHODS: We compared rounded and conventional waveforms with equal peak voltages. Eighty-five shocks of 50 to 500 V were delivered to 10 patients requiring atrial cardioversion for persistent atrial fibrillation. The patient touched an analog pain scale (0-15 cm) and orally reported a pain score on a scale from 0 to 5. An observer scored thoracic contractions on a scale from 0 to 5. RESULTS: No differences between the rounded and conventional waveform on any scale were noted for either univariate or multivariate analyses. However, all three response scales were strongly predicted by voltage with r(2) = 0.77 (oral), r(2) = 0.86 (analog), and r(2) = 0.85 (contraction) after correcting for patient variability and including a log voltage term. CONCLUSIONS: Patient pain perception was determined primarily by waveform peak voltage and not by the rounding, per se.

Adult↗
PubMed2005

Cardiac resynchronization therapy: effects on left and right ventricular ejection fraction during exercise.

In patients with heart failure and wide QRS complex, cardiac resynchronization therapy (CRT) is associated with improvement of symptoms and cardiac function. This study examined the effects of a 3-month period of CRT on left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and on LV volumes, both at rest and during exercise. A CRT system was implanted in 15 patients with severe heart failure and wide QRS. Before implant and 3 months later, all patients underwent assessment of cardiac performance with equilibrium Tc(99) radionuclide angiography with imaging in the best septal left anterior oblique view. Exercise was performed on a bicycle ergometer. At 3 months, a significant improvement in New York Heart Association functional class was observed, and radionuclide angiography showed a significant decrease in LV volumes and a significant increase in LVEF at rest, as well as a significant increase in LVEF during exercise. The remodeling processes associated with CRT did not appear to include RV function, since RVEF did not improve, and changes in RVEF did not correlate with changes in LVEF, neither at rest nor during exercise.

Cardiac Pacing, Artificial↗