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Simultaneous stimulation of 2 left ventricular (LV) sites could enhance the effectiveness of cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the acute hemodynamic response to dual-site LV CRT. Two LV pacing leads were successfully implanted in 12 CRT candidates (New York Heart Association classes III to IV, QRS >or=120 ms). Target positions were the lateral or posterolateral vein (site A) and anterior or anterolateral vein (site B). A conductance catheter was placed in the left ventricle for pressure-volume measurements. Tested CRT configurations were alternated by atrial overdrive pacing at a fixed rate and included site A and B single-site CRT and dual-site LV CRT (2 LV sites plus right ventricular apex) at 4 atrioventricular intervals. Overall, single-site LV CRT significantly enhanced stroke volume, stroke work, maximum pressure derivative, and conductance-derived indexes of LV synchrony when delivered in site A, whereas no significant changes were noticed with pacing in site B. Specifically, site-A pacing resulted in a higher stroke volume increase (LV pacing site associated with the best hemodynamic response [best-LV]) in 8 patients, and site-B pacing, in 4 patients. At intermediate atrioventricular intervals, dual-site LV CRT resulted in improved stroke volume, stroke work, maximum pressure derivative, and LV synchrony with respect to single-site CRT when delivered at the best-LV (all p <0.05). However, single-site CRT at best-LV produced results similar to dual-site LV CRT when the atrioventricular interval was optimized in each patient. In conclusion, adding a second LV lead does not result in further improvement in acute hemodynamic response with respect to standard CRT when the single LV pacing site and atrioventricular interval are optimal.

Aim: Gender related differences in epidemiology, treatment, and prognosis of heart failure (HF) have been reported. We examined the sex influence in patients treated with cardiac resynchronization therapy (CRT)., Methods and Results: Out of 334 consecutive HF patients (19.7% women) who underwent CRT, 195 patients reached clinical and echocardiographic evaluation at six and 12 months and were selected for analysis. A reduction in left ventricular (LV) end-diastolic volume/m(2) (EDVi) and end systolic volume/m(2) (ESVi) was evident in the overall population at six months (P < 0.001) and from six to 12 months (P < 0.001). Compared to men, women showed significantly greater changes in LV volumes at mid (P < 0.05) and long-term (P < 0.001) follow-up and a significantly higher LV ejection fraction (EF) (40.8 +/- 12.3 vs 34.1 +/- 10.1, P < 0.01) at one year. Multiple regression analysis, including several demographic and clinical parameters, revealed that female gender is independently associated with greater reduction in LV ESVi. At the 12-month follow-up, the proportion of responders (defined in terms of ESV reduction by at least 10%) was higher in women than in men (76.1% vs 59.3%, P < 0.05)., Conclusions: CRT induced a gender specific LV remodeling response.

Congenital atrioventricular block is a rare, but severe occurrence in the newborn can be related to various cardiac malformations or to maternal autoimmune diseases, particularly systemic lupus erythematosus. We report an extremely low-birth-weight infant affected by congenital heart block, due to positive anti-RO/SSA and anti-LA/SSB antibodies of the mother, with progressively increasing respiratory distress syndrome and heart failure. The infant was successfully treated with an external constant-current, single-chamber ventricular (VVI) temporary epicardial pacing, placed on the second day of life, at the weight of 810 g. After this treatment, cardiac failure resolved and respiratory assistance could be rapidly stopped. A single-chamber, rate-responsive, permanent pacemaker was placed at 3 months of life with steroid-eluting, epicardial-pacing leads. We emphasize that early extrathoracic temporary epicardial pacing is able to resolve heart failure in an extremely low-birth-weight infant.

Background: Inflammatory markers are involved in heart failure (HF) pathophysiology. However, the link between these markers and reverse remodeling as well as major adverse cardiac events (HF death, sudden death, and unplanned cardiac rehospitalizations) in patients who undergo cardiac resynchronization therapy (CRT) has not been evaluated., Methods and Results: We recorded major adverse cardiac events of 140 patients (on optimized medical therapy, left ventricular ejection fraction 29.9 +/- 9.6%, New York Heart Association Class III-IV, with intraventricular dyssynchrony) who underwent CRT (enrolled since April 2004). Moreover, we evaluated before and after 6 months of CRT: interleukin-6, high-sensitivity C-reactive protein, New York Heart Association class, quality of life (score on Minnesota Living with Heart Failure questionnaire), 6-minute walking test, left ventricular end-diastolic and end-systolic volumes (nonindexed and indexed by body surface area), and left ventricular ejection fraction. Adverse cardiac events were observed in 40 patients (28.6%): 22 deaths and 18 cardiac unplanned rehospitalizations. Only patients without adverse events during follow-up showed a significant reduction of inflammatory markers and left ventricular volumes (reverse remodeling), despite a significant improvement of clinical status observed in both groups of patients., Conclusions: The reduction of inflammatory status seems to be linked to reverse remodeling as well as to a better clinical prognosis in patients with HF who underwent CRT.

Objectives: We compared left ventricular (LV) systolic and diastolic function during right ventricular (RV), LV, and biventricular (BiV) pacing in patients with narrow QRS duration with and without LV dysfunction., Background: The optimal RV pacing lead location for patients with a standard indication for ventricular pacing remains controversial., Methods: Left ventricular pressure and volume data were determined via conductance catheter during electrophysiology study in 31 patients divided into groups with ejection fraction (EF) > or =40% (n = 17) or EF <40% (n = 14). QRS duration was 91 +/- 18 versus 106 +/- 25 ms, respectively (p = NS). Hemodynamic data were recorded during atrial and dual chamber pacing from the RV apex, RV free wall, RV septum, LV free wall, and BiV., Results: In patients with EF > or =40%, RV pacing at 1 or more sites, but not LV free wall or BiV pacing, significantly (p < 0.05) impaired cardiac output (CO), stroke work (SW), EF, and LV relaxation compared with atrial overdrive pacing. Right ventricular pacing also impaired hemodynamics and LV function in patients with EF <40%. However, LV and BiV pacing increased CO, SW, EF, and LV +dP/dt(MAX) in patients with LV dysfunction. Left ventricular and BiV pacing enhanced an index of global LV cycle efficiency in patients with depressed EF. The detrimental hemodynamic effects of RV pacing were attenuated by selecting the optimal RV pacing site., Conclusions: Right ventricular pacing worsens LV function in patients with and without LV dysfunction unless the RV pacing site is optimized. Left ventricular and BiV pacing preserve LV function in patients with EF >40% and improve function in patients with EF <40% despite no clinical indication for BiV pacing.

Background: Cardiac resynchronization therapy (CRT) is an emerging treatment for heart failure patients with left bundle branch block; in these patients left ventricle filling pattern (LVFP) abnormalities are recognized as cause of symptoms and predictors of outcome. We investigated the effects of CRT on diastolic function and the prognostic value of LVFP in patients on CRT., Methods: 65 patients treated with CRT were studied over a 12 months period. At baseline, according to defined echocardiographic criteria, restrictive LVFP (RFP) was present in 25 patients, whereas 40 patients showed no-RFP., Results: After CRT, opposite changes occurred in the two groups. In no-RFP patients, early-to-atrial filling velocity ratio (E/A) increased from 0.8+/-0.3 to 1.0+/-0.6 (p=0.006) and E wave deceleration time (DT) decreased from 234+/-83 ms to 196+/-51 ms (p=0.028). In 13 RFP patients, E/A decreased from 2.2+/-0.9 to 0.8+/-0.5 and DT increased from 128+/-43 ms to 205+/-52 ms (both p<0.001), leading to reversal of RFP. In both groups, clinical, functional and echographic benefits were evident, with mortality rates of 5% (2/40) and 15% (2/13) respectively. The remaining patients showed persistence of RFP (E/A and DT unchanged), no improvement and a mortality rate of 42% (5/12) (p=0.005, versus no-RFP)., Conclusions: CRT improves diastolic function, inducing also reversal of LVFP in a consistent number of RFP patients. The persistence of RFP after CRT is associated to an extremely poor prognosis.

Aims: In patients with atrial fibrillation right ventricular pacing can block antegrade conduction at pacing intervals longer than the shortest spontaneous R-R interval, causing the stabilization of ventricular rhythm. In this study the effects of pacing at two sites were compared in order to evaluate the role of conduction times in determining the stabilization of ventricular rhythm., Methods: In eight patients with permanent atrial fibrillation, the ventricular rate was recorded before and during pacing at the right ventricular apex and the His bundle with different cycle lengths., Results: In all patients, we obtained a reduction in spontaneous QRS complexes with respect to those anticipated at pacing rates slightly above the spontaneous mean rate, and the ventricular rhythm stabilized at pacing intervals longer than the spontaneous shortest R-R intervals. Between pacing sites we did not observe any difference in the reduction in spontaneous beats and the cycle stabilizing the rhythm. Moreover, simulation of the interaction between antegrade and retrograde impulses in a computer model confirmed that results obtained by pacing at the His bundle cannot be readily explained as a consequence of conduction delays., Conclusion: This study suggests that the lag introduced by the His-Purkinje conduction cannot explain, as proposed, the stabilization of ventricular rhythm observed in patients with atrial fibrillation and right ventricular pacing.

In 21 patients implanted with a biventricular pacing device with programmable interventricular delay (VVd), the myocardial performance index (MPI) was evaluated during spontaneous sinus rhythm, simultaneous biventricular pacing, and sequential biventricular pacing at different VVds and atrioventricular delays (AVds). The AVd-VVd combination associated with the minimum MPI defined patient-tailored biventricular pacing. Simultaneous biventricular pacing significantly improved MPI compared with spontaneous sinus rhythm. An additional improvement was obtained by tailored biventricular pacing. The optimal AVds were significantly shorter during right ventricular preactivation than during left ventricular preactivation.

Atrial fibrillation (AF) and congestive heart failure (CHF) share several characteristics and often coexist in the same patient. Both are responsible for significant morbidity and mortality, are increasing in prevalence, and are major sources of health expenditure. The Management of Atrial fibrillation Suppression in AF-HF COmorbidity Therapy (MASCOT) study is a European, single-blind, prospective, controlled, multicentre, randomized clinical trial designed to examine whether adding the AF Suppression Algorithm to cardiac resynchronization therapy (CRT) improves the prognosis of patients with CHF. The patients will be randomly assigned to a CRT-only group, with the AF Suppression algorithm programmed OFF (control group), versus a CRT+AF Suppression group, with the algorithm programmed ON (treatment group). The primary study endpoint is development of permanent AF, and secondary endpoints are safety of the AF Suppression algorithm, and evolution of multiple clinical variables over 24 months of follow-up. CRT combined with a refined atrial tachyarrhythmia prevention pacing algorithm may represent a major advance in the management of AF and CHF by electrical stimulation.

Atrial pacing may prevent the onset of atrial fibrillation (AF) because of: (1) prevention of the relative bradycardia that triggers paroxysmal AF; (2) prevention of the bradycardia induced dispersion of refractoriness; (3)suppression or reduction of premature atrial contractions that initiate reentry and predispose to AF; (4) preservation of AV synchrony, which might prevent switch induced changes in atrial repolarization predisposing to AF. Atrial pacing locations that decrease atrial activation and dispersion of refractoriness may be preferable in patients with a history of AF. Two different interatrial septum sites have been proposed: the Bachmann's bundle and the coronary sinus ostium. The results of two prospective randomized studies indicate that septal pacing, when compared to the traditional right atrial appendage pacing, significantly reduces : (1) paroxysmal AF recurrences and burden; and (2) progression to chronic AF.

Unlabelled: Cardiac resynchronization therapy (CRT) by biventricular pacing is indicated in patients with severe heart failure and left bundle branch block who remain symptomatic despite optimal medical therapy. The relationship between baseline resting perfusion pattern and hemodynamic response to CRT has not been fully investigated. We tested the usefulness of perfusion gated SPECT for baseline evaluation and follow-up of these patients., Methods: In 20 patients, we performed gated SPECT before CRT and at the 3-mo follow up. Left ventricular (LV) ejection fraction (EF), end-diastolic (ED) and end-systolic (ES) volume indexes (VI), and wall motion score index (WMSI) were measured and compared with clinical outcome., Results: One patient died before follow-up. The 19 remaining patients were classified into 1 of 2 groups according to the presence (group A) or absence (group B) of a significant severe perfusion defect at baseline before CRT. At the 3-mo follow-up, 6 of 10 group A and 8 of 9 group B patients had an improvement in New York Heart Association class. In both groups, quality of life, 6-min walking distance, and WMSI significantly improved. In group A, no significant change was registered in LVEF, LVEDVI, or LVESVI. In group B, LVEF increased from 23.1% +/- 8% to 27.1% +/- 11% (P < 0.03) and LVEDVI and LVESVI decreased from 159 +/- 70 mL to 135 +/- 68 mL (P < 0.02) and from 127 +/- 67 mL to 104 +/- 65 mL (P < 0.01), respectively., Conclusion: Perfusion gated SPECT appears useful to characterize and follow up candidates for CRT. Despite clinical improvement, patients with severe resting perfusion defects do not show significant improvement in LVEF or reduction in LV volumes.

Closed-loop stimulation (CLS) is a physiological system for adaptive rate pacing based on monitoring and processing of the intracardiac impedance. The "standard" CLS algorithm (SCLS) requires continuous ventricular pacing. A new, enhanced CLS algorithm (ECLS) provides rate modulation during sensed and paced ventricular depolarizations. The aim of this study was to validate ECLS and to compare its effectiveness with that of SCLS. Ten patients received Inos2+ CLS pulse generators. SCLS and ECLS were uploaded to the device and evaluated in a randomized, crossover fashion at 30 and 45 days after pacemaker implantation. At each follow-up visit, ambulatory and posture tests were performed. Heart rate (HR) during daily activity was evaluated based on 24-hour Holter recordings. During all phases of the ambulatory test, both algorithms provided physiologically appropriate rates in all patients. The proportion of sensed ventricular events was significantly higher in ECLS (93.9%) than in SCLS (0.7%). The proportion of paced ventricular events during 24 hours was substantially lower with ECLS (25.7%) than with SCLS (98.4%). Postural changes did not influence HR with either algorithm. The Holter recordings indicated prompt, safe, and effective rate modulation appropriate to patients activity. In conclusion, analysis of these clinical data demonstrated the safety and effectiveness of the ECLS algorithm. Moreover, with this algorithm the ventricle is paced only when required, which may be expected to retard battery depletion and retain the natural ventricular activation pattern whenever possible.

Aims: Biventricular pacing (BVP) can improve haemodynamics in patients with dilated cardiomyopathy (DCM) and left bundle branch block by reducing interventricular delay (IVD). Since in DCM interatrial delay (IAD) and IVD frequently coexist, the aim of this study was to test the hypothesis that IVD reduction associated with IAD produces an imbalance between the programmed right atrioventricular (AV) delay and the effective AV delay on the left, and that interatrial septum pacing (IASP) combined with BVP overcomes this adverse effect., Methods and Results: IAD, IVD, left and right mechanical atrioventricular delay (L-RMAVD) were measured by echo-Doppler in 29 patients with BVP: 17 patients (Group A) had the atrial lead in the right atrial appendage, 12 patients (Group B) who experienced paroxysmal atrial fibrillation had the atrial lead on the interatrial septum. In Group A, LMAVD was significantly shorter than RMAVD (172 +/- 24 vs 207 +/- 24 ms, P<0.002), IAD was significantly longer than IVD (52 +/- 24 vs 21 +/- 18 ms, P<0.0001). In Group B, no differences were observed between LMAVD and RMAVD (187 +/- 32 vs 185 +/- 28 ms, NS), and between IAD and IVD (11 +/- 12 vs 13 +/- 16 ms, NS)., Conclusions: IAD produces different left and right atrioventricular sequences in BVP. IASP combined with BVP, by resynchronizing both atria and ventricles, is able to avoid this adverse effect.