[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the association between circulating (CPCs) and endothelial (EPCs) progenitor cells and left ventricular (LV) remodeling in chronic heart failure (HF). 85 HF patients, ranging 29-89 years, 83.5 % males, 45.9 % ischemic, NYHA functional class II-IV, with a LV ejection fraction ≤40 % were studied. LV ejection fraction, LV end-diastolic and end-systolic (LVESV) volumes, LV mass and tricuspid annular plane systolic excursion (TAPSE) were evaluated, and, when indicated, indexed for body surface area (BSA). CPCs and EPCs number was assessed using flow cytometry. CPCs were defined as CD34+, CD133+ and CD34+/CD133+. EPCs, identified through their expression of KDR, were defined as CD34+/KDR+, CD133+/KDR+ and CD34+/CD133+/KDR+. All EPCs were negatively related to LVESV/BSA (r = -0.24, p = 0.02 for all EPC's populations), and to LVmass/BSA (CD34+KDR+; r = -0.30, p = 0.005; CD133+KDR+; r = -0.31, p = 0.004; CD34+CD133+KDR+; r = -0.29, p = 0.007). No differences in EPCs levels in relation to cardiovascular risk factors, medications, etiology, age or gender were observed. CPCs number was higher in women, and lower in ischemic patients. In logistic regression analyses, the low EPCs' number was associated with an increased likelihood of abnormal LVmass/BSA. CPCs proved to be higher and EPCs lower in patients with severely abnormal LVmass/BSA (gr/m(2), ≥122 in women and ≥149 in men). Our results suggest a correlation between LV remodeling and progenitor cells. This is noteworthy considering that it has been suggested that bone marrow-derived EPCs participate in cardiac regeneration and function recovery in the setting of progressive HF.
Internal and Emergency Medicine 11/2014; 10(3). DOI:10.1007/s11739-014-1149-5 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PurposeLeft ventricular (LV) torsion is an important parameter of LV performance and can be influenced by several factors. Aim of this investigation was to evaluate whether QRS prolongation in left bundle branch block (LBBB) may influence global LV twist and twisting/untwisting rate in chronic systolic heart failure (HF) patients.Methods
We prospectively evaluated 30 healthy subjects (control group) and 100 chronic HF patients with severely impaired LV systolic function (ejection fraction ≤35%). Patients were divided into three groups according to QRS duration: A: QRS < 120 ms (n 49), B: 120 ≤ QRS ≤ 150 ms (n 28) and C: QRS > 150 ms (n 23). Patients in groups B and C presented LBBB. All subjects underwent standard trans-thoracic echocardiography and two-dimensional speckle-tracking echocardiography evaluation. Categorical variables were compared by the chi-square or the Fisher's exact test. Continuous variables were compared using the ANOVA test. Correlations between variables were analysed with linear regression.ResultsControl subjects presented higher torsion parameters, when compared with patients in any HF group. Among the three HF groups, no differences were detected in global twist (4·79 ± 3·54, 3·8 ± 3·0 and 4·15 ± 3·14 degrees, respectively), twist rate max (44·81 ± 25·03, 37·94 ± 19·09 and 37·61 ± 24·49 degrees s−1, respectively) and untwist rate max (−36·31 ± 30·89, −27·68 ± 34·67 and −39·62 ± 26·27 degrees s−1, respectively) (P>0·05 for all). At linear regression analysis, there was no relation between QRS duration and any torsion parameter (P>0·05 for all).Conclusions
In patients with chronic severe systolic heart failure, QRS duration and LBBB morphology do not affect LV twisting and untwisting.
[Show abstract][Hide abstract] ABSTRACT: Cryoablation (CA) emerged as an alternative procedure to radiofrequency (RF). The aim of this study was to compare haemostatic system alterations in patients undergoing RF or CA for atrioventricular nodal reentrant tachycardia ablation. von Willebrand factor (vWF), spontaneous whole blood platelet aggregation, prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor type-1 (PAI-1), and clot lysis time (CLT) were determined in 48 patients (27 CA; 21 RF; 19M/29F, mean age 49.6 ± 17.6 years). Blood samples were obtained before the procedure (T0), immediately after (T1), and 24 h later (T2). At T1 both procedures were associated with a significant increase in levels of the endothelial activation marker vWF. At T2 vWF levels were lower in CA than in RF group. No changes in whole blood platelet aggregation before and after ablation procedures were observed. At T1 both groups determined an increase in blood clotting activation markers, F1 + 2, TAT, and DD. At T2 F1 + 2, TAT and DD levels were similar to baseline values. The comparison between RF and CA showed no significant differences in F1 + 2 and TAT levels, whereas at T1 DD levels were higher in CA group than in RF group. Both procedures induced a significant decrease in CLT, whereas no changes in PAI-1 levels were found. There were no significant differences in CLT and PAI-1 levels. The fibrinolytic efficiency analysis showed that at T1 DD/TAT and DD/F1 + 2 ratios were lower in RF group and remained lower in RF than in CA group at T2. CA procedure may be associated with a lower degree of endothelial damage and with a higher fibrinolytic capacity respect to RF.
Internal and Emergency Medicine 06/2014; 9(8). DOI:10.1007/s11739-014-1090-7 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolomic, a systematic study of metabolites, may be a useful tool in understanding the pathological processes that underlie the occurrence and progression of a disease. We hypothesized that metabolomic would be helpful in assessing a specific pattern in heart failure patients, also according to the underlining causes and in defining, prior to device implantation, the responder and nonresponder patient to cardiac resynchronization therapy (CRT).
In this prospective study, blood and urine samples were collected from 32 heart failure patients who underwent CRT. Clinical, electrocardiography and echocardiographic evaluation was performed in each patient before CRT and after 6 months of follow-up. Thirty-nine age and sex-matched healthy individuals were chosen as control group. For each sample, 1H-NMR spectra, Nuclear Overhauser Enhancement Spectroscopy, Carr-Purcell-Meiboom-Gill and diffusion edited spectra were measured.
A different metabolomic fingerprint was demonstrated in heart failure patients compared to healthy controls with high accuracy level. Metabolomics fingerprint was similar between patients with ischemic and nonischemic dilated cardiomyopathy. At 6-month follow-up, metabolomic fingerprint was different from baseline. At follow-up, heart failure patients' metabolomic fingerprint remained significantly different from that of healthy controls, and accuracy of cause discrimination remained low. Responders and nonresponders had a similar metabolic fingerprint at baseline and after 6 months of CRT.
It is possible to identify a metabolomic fingerprint characterizing heart failure patients candidate to CRT, it is independent of the different causes of the disease and it is not predictive of the response to CRT.
Journal of Cardiovascular Medicine 04/2014; 15(4). DOI:10.2459/JCM.0000000000000028 · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Italy tens of thousands of patients undergo implantation or replacement of cardiac implantable electronic devices (CIEDs) annually, and up to 50% of these subjects receive antiplatelet agents or oral anticoagulants. The rate of CIED-related complications, mainly infective, has also significantly increased, so that transvenous lead extraction procedures are often required. CIED surgery is peculiar and portends specific intrinsic risks of developing life-threatening hemorrhagic complications; on the other hand periprocedural discontinuation of antithrombotic therapy in patients at high thromboembolic risk may have catastrophic consequences. Accordingly, the management of candidates to CIED surgery who receive concomitant antithrombotic therapy is of great clinical relevance, though controversial and only partially, if not at all, adequately addressed in current evidence-based guidelines. Although for many procedures the administration of aspirin alone or continuation of anticoagulant therapy seems reasonably safe, with use of bridging therapy with parenteral heparins restricted to selected cases, there are multiple variables that may make therapeutic choices challenging. The aim of the present position paper is to provide practical recommendations for the management of antithrombotic therapy in patients undergoing CIED surgery by defining indications for a systematic approach integrating general technical considerations with patient-specific elements based on a careful evaluation of the balance between hemorrhagic and thromboembolic risk. The decision-making process applied in this document relies on the stratification of the procedural hemorrhagic risk and of the risk deriving from discontinuation of antiplatelet or anticoagulant therapy combined to produce different clinical scenarios with specific indications for optimal management of periprocedural antithrombotic therapy.
Giornale italiano di cardiologia (2006) 02/2014; 15(1):56-72. DOI:10.1714/1394.15520
[Show abstract][Hide abstract] ABSTRACT: There have been substantial progresses in the technology of cardiac implantable electric devices (CIEDs) during the past decades. One of the progresses is represented by the development of a hemodynamic sensor embedded at the tip of a pacing lead that measures myocardial contractility by the analysis of myocardial mechanical vibrations occurring during the cardiac cycle. This sensor, providing continuous hemodynamic monitoring, could play an important role in clinical practice because of several clinical applications in CIEDs recipients. The objectives of this work are to report how this sensor operates and to review the main findings about its clinical applications.
[Show abstract][Hide abstract] ABSTRACT: AimsCHADS2 and CHA2DS2-VASc scores are pivotal in assessing the risk of stroke in atrial fibrillation patients, and were recently proved to predict hospitalizations and mortality in specific clinical settings. Aim of this study was to evaluate whether these scores could predict clinical outcomes [first hospitalization for heart failure (HF) and a combined event of HF hospitalization and death for any cause] in patients candidates to cardiac resynchronization therapy and implantable defibrillator (CRT-D).Methods and resultsIn a retrospective multicentre Italian study, we enrolled 559 consecutive HF patients candidates to CRT-D, and we grouped them in three pre-specified risk classes: low (CHADS2/CHA2DS 2-VASc 1-2), moderate (CHADS2/CHA2DS 2-VASc 3-4), and high (CHADS2 5-6/CHA2DS 2-VASc 5-8). All patients underwent regular follow-up at implanting centres every 6 months; data collection was extended till the 72th month of follow-up. At a median FU of 30 months, 143 patients (25.4%) were hospitalized for HF and 110 (19.5%) died. Event-free survival analysis showed a significant difference according to baseline CHADS2 and CHA2DS 2-VASc scores (Log-Rank for HF P < 0.001 for CHADS2 and CHA2DS2-VASc; Log-Rank for combined end-point P = 0.001 for CHADS2, P < 0.001 for CHA2DS2-VASc). At multivariate analysis, independent predictors of endpoints were: previous atrial fibrillation (AF) or AF at implant, NYHA class, QRS duration and the CHA 2DS2-VASc score (for HF hospitalization P = 0.013; for the combined event, P = 0.007), while the CHADS2 score was not independently associated with either the end-points.Conclusion
In CRT-D patients, pre-implant CHA2DS2-VASc score is an independent predictor of major clinical events at 30-month follow-up.
[Show abstract][Hide abstract] ABSTRACT: Background: In experimental models, ranolazine exerts a synergistic effect which enhances amiodarone's potential to suppress atrial fibrillation (AF). The clinical effect of ranolazine added to amiodarone for AF conversion has only undergone minimal investigation.
Purpose: This study compared the safety and effectiveness of ranolazine in combination with amiodarone versus amiodarone alone for conversion of paroxysmal AF.
Methods: We prospectively enrolled all consecutive patients with paroxysmal AF who were deemed eligible for pharmacologic cardioversion. Exclusion criteria were QTc>440msec, hepatic, renal, or thyroid disorders, acute coronary syndrome, prior use of ranolazine, and use of strong CYP3A inhibitors which could affect ranolazine's metabolism. Patients were randomized to either iv amiodarone alone (loading dose of 5md/kg followed by a maintenance dose of 50mg/h for 24h), or to the combination of iv amiodarone plus a single oral dose of ranolazine 1500mg. Patients remained on continuous ECG monitoring. We measured the time to conversion to sinus rhythm, and the proportion of patients with AF conversion within 12h and within 24h.
Results: 72 patients were enrolled (mean age 59±7 years): 35 in the amiodarone-only group and 37 in the amiodarone plus ranolazine combination group. The two groups did not differ in terms of clinical characteristics and echocardiographic parameters, including left atrium diameter. Time to conversion was shorter in the combination group compared with the amiodarone-only group (8.4±3.8h vs.15.1±4.8 h; p<0.001). Conversion was achieved in more patients in the combination group as compared to the amiodarone-only group (57% vs. 20% at 12h, respectively, p=0.001; and 86% vs. 68% at 24h, respectively, p=0.07). There were no cases of excessive QT prolongation (>550msec) and no proarrhythmic events in either treatment group.
Conclusions: The addition of ranolazine to standard amiodarone treatment is safe, and it leads to faster conversion of paroxysmal AF. Consistent with substantial preclinical research on ranolazine's AF-suppressing potential, the present clinical study demonstrates a synergistic effect of ranolazine and amiodarone for conversion of paroxysmal AF.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Left bundle branch block (LBBB) is frequently observed in heart failure (HF) patients, and is recognized as both an adverse prognostic factor and a key-element for referring patients to cardiac resynchronization therapy (CRT). It has been previously defined as concordant (cLBBB) or discordant (dLBBB) when associated with a positive or negative T wave in leads I and V5-V6, respectively. Recently, dLBBB has been shown to be associated with a worse clinical, neurohormonal, and prognostic profile in systolic HF patients. Our aim was to evaluate the impact of CRT on the prognostic value of LBBB morphology in a population of systolic HF.
Methods: A total of 406 consecutive systolic HF patients with LBBB (age 69±9 years, left ventricular ejection fraction, 26±6%), treated with CRT (CRT-P, n= 78; CRT-D, n= 328) from three Italian Centers underwent clinical, biohumoral, and echocardiographic characterization. All patients were then followed-up for cardiac events (median 31 months, range 1-137).
Results: cLBBB was observed in 110 (27%) patients, dLBBB in 296 (73%). dLBBB was more frequent in patients with ischemic cardiomyopathy and associated with a shorter QRS duration and worse glomerular filtration rate (all p <0.05). No difference in pharmacological and device therapy was observed, except for a higher use of diuretics in dLBBB patients. At Kaplan-Meier analysis, dLBBB was associated with a worse prognosis for the composite end-point of sudden death and ICD shock (p<0.05), while no difference was observed in terms of either cardiac death or death due to HF progression.
Conclusions: dLBBB, despite CRT, is associated with the occurrence of sudden death and implantable cardioverter defibrillator shock in systolic HF patients, identifying a subset with higher arrhythmic risk, needing an enhanced, targeted therapeutical effort.
Journal of the American College of Cardiology 03/2013; 61(10). DOI:10.1016/S0735-1097(13)60668-3 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Previous studies have reported that the left ventricular (LV) pacing site is a major determinant of the hemodynamic response to cardiac resynchronization therapy (CRT). However, lead positioning in a lateral or posterolateral cardiac vein may not be optimal for every patient. The objective of this study was to assess the relationship between the right ventricular (RV)-to-LV conduction time and the systolic function during CRT on the basis of changes to LV pressure-volume loops.
Left ventricular pressure and volume data were determined using a conductance catheter during CRT device implantation in 10 patients. Four endocardial LV sites were systematically assessed at four atrioventricular delays. The RV-to-LV conduction time was measured as the time interval between spontaneous peak R waves, recorded through the RV lead and the LV catheter.
The optimal pacing site varied among patients. However, the pacing site associated with the maximum RV-to-LV conduction time resulted in a stroke volume improvement comparable to the pacing site identified through individual hemodynamic optimization (41 ± 17 mL vs 44 ± 18 mL, P = 0.266). Moreover, the RV-to-LV conduction time recorded at each endocardial pacing site correlated positively with the increase in stroke volume (r = 0.537; P < 0.001), stroke work (r = 0.642; P < 0.001), and the pressure-derivative maximum (r = 0.646; P < 0.001) obtained with CRT.
An optimal acute response to CRT can be obtained by positioning the LV lead at the site associated with the maximum RV-to-LV conduction time. A significant correlation appears to exist between RV-to-LV conduction time and the improvement in systolic function with CRT.
[Show abstract][Hide abstract] ABSTRACT: Smoking is associated with increased morbidity and mortality in cardiac patients. However, data on the prognostic impact of smoking in heart failure (HF) patients on cardiac resynchronization therapy with defibrillator (CRT-D) are absent. We investigated the effects of smoking on all-cause mortality and on a composite endpoint (all-cause death/appropriate device therapy), appropriate and inappropriate device therapy, in 649 patients with HF who underwent CRT-D between January 2003 and October 2011 in 6 Centers (4 in Italy and 2 in USA). 68 patients were current smokers, 396 previous-smokers (patients who had smoked in the past but who had quit before the CRT-D implant), and 185 had never smoked. The risk of each endpoint by smoking status was evaluated with both Kaplan-Meier and Cox proportional-hazard analysis. After adjusting for age, left ventricular ejection fraction, QRS width and ischemic etiology, both current and previous smoking were independent predictors of all-cause death [HR = 5.07 (95 % CI 2.68-9.58), p < 0.001 and HR = 2.43 (95 % CI 1.38-4.29), p = 0.002, respectively) and of composite endpoint [HR = 1.63 (1.04-2.56); p = 0.033 and HR = 1.46 (1.04-2.04) p = 0.027]. In addition, current smokers had a significantly higher rate of inappropriate device therapy compared to never smokers [HR = 21.74 (4.53-104.25), p = 0.005]. Our study indicates that in patients with HF who received a CRT-D device, current and previous smoking increase the event rate per person-time of death and of appropriate and inappropriate ICD therapy more than other known negative prognostic factors such as age, left ventricular dysfunction, prolonged QRS duration and ischemic etiology.
Internal and Emergency Medicine 12/2012; 9(3). DOI:10.1007/s11739-012-0891-9 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spontaneous behavior of ventricular extrasystoles (VE) was analysed. From a database containing 578 athletes with VE, 84 males and 11 females (29.9 ± 18.1 years) having ≥ 100 VE or repetitive VE [ventricular couplets (VC) or ventricular tachycardias (VT)] at first 24-hour Holter electrocardiographic monitoring (24-h-HM) (baseline) and at least 1-year of follow-up (3.1 ± 2.2 years) over the past 10 years were selected. The baseline was compared with the last 24-h-HM to establish DVE (VE reduction of at least 98%/24 h in the absence of VC or VT). SDVE was calculated as standard deviation of the number of VE on serial 24-h-HMs. DVE and SDVE were considered as dependent variables. Independent variables were: age, sex, type of sport, symptoms, baseline VE rate (BVE), baseline VC and VT, VE morphology, VE behavior during the baseline training session, disqualification from competitive sports, echocardiographic abnormalities. DVE occurred in 32 athletes (34%). SDVE varied from 0 to 12 658 VE/24 h (1916 ± 2649.9). Disappearance of VE during the baseline training session (DVET) correlated to DVE (P = 0.0319). BVE directly correlated to SDVE (P = 0.0008). Athletes' VE are highly variable over time, their variability depending on BVE, and they not infrequently tend to disappear. The only useful variable for predicting DVE is DVET.
Scandinavian Journal of Medicine and Science in Sports 09/2012; 24(2). DOI:10.1111/j.1600-0838.2012.01526.x · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During cardiac resynchronization therapy (CRT) device implantation, the pacing lead is usually positioned in the coronary sinus (CS) to stimulate the left ventricular (LV) epicardium. Transvenous LV endocardial pacing via transseptal puncture has been proposed as an alternative method. In the present study, we evaluated the acute hemodynamic effects of CRT through LV endocardial pacing in heart failure patients by analyzing LV pressure-volume relationships.
LV pressure and volume data were determined via conductance catheter during CRT device implantation in 10 patients. In addition to the standard epicardial CS pacing, the following endocardial LV sites were systematically assessed: the site transmural to the CS lead, the LV apex, the septal midwall, the basal lateral free wall, and the midlateral free wall. Four atrioventricular delays were tested. There was a significant improvement of systolic function with CRT in all LV pacing configurations, whereas no differences in systolic or diastolic function were detected between LV epicardial and endocardial transmural sites. The optimal pacing site varied among patients but was rarely related to relatively longer activation delays, as assessed by analyzing endocardial electric activation maps. Nonetheless, positioning the pacing lead at the optimal endocardial LV site in each patient significantly improved LV performance in comparison with conventional CS site stimulation (stroke volume, 83 [79-112] mL versus 73 [62-89] mL; P=0.034).
Pacing at the optimal individual LV endocardial site yields enhanced LV performance in comparison with conventional CS site stimulation. Endocardial LV pacing might constitute an alternative approach to CRT, when CS pacing is not viable.