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Background: The Seattle Heart Failure Model (SHFM) is a multimarker risk assessment tool able to predict outcome in heart failure (HF) patients. Aim: To assess whether the SHFM can be used to risk-stratify HF patients who underwent cardiac resynchronization therapy with (CRT-D) or without (CRT) an implantable defibrillator. Methods and Results: The SHFM was applied to 342 New York Heart Association class III-IV patients who received a CRT (23%) or CRT-D (77%) device. Discrimination and calibration of SHFM were evaluated through c-statistics and Hosmer-Lemeshow (H-L) goodness-of-fit test. Primary endpoint was a composite of death from any cause/cardiac transplantation. During a median follow-up of 24 months (25th–75th percentile [pct]: 12–37 months), 78 of 342 (22.8%) patients died; seven patients underwent urgent transplantation. Median SHFM score for patients with endpoint was 5.8 years (25th–75th pct: 4.25–8.7 years) versus 8.9 years (25th–75th pct: 6.6–11.8 years) for those without (P < 0.001). Discrimination of SHFM was adequate for the endpoint (c-statistic always ranged around 0.7). The SHFM was a good fit of death from any cause/cardiac transplantation, without significant differences between observed and SHFM-predicted survival. Conclusion: The SHFM successfully stratifies HF patients on CRT/CRT-D and can be reliably applied to help clinicians in predicting survival in this clinical setting. (PACE 2012; 35:88–94)

Aims It has been shown that atrioventricular (AV) delay optimization improves cardiac resynchronization therapy (CRT) response. Recently, an automatic algorithm (QuickOpt™, St Jude Medical), able to quickly identify the individual optimal AV interval, has been developed. The algorithm suggests an AV delay based on atrial intracavitary electrogram (IEGM) duration. We hypothesized that the difference between electrical and mechanical atrial delays could affect the effectiveness of QuickOpt method. The aim of this study was to test this hypothesis in 23 CRT patients who were recipients of St. Jude Medical devices. Methods and results Using echocardiography, aortic flow velocity time integral (VTI) was evaluated at baseline, at QuickOpt suggested AV delay and after reducing it by 25 and 50%. Mechanical inter-atrial delay (MIAD) derived from echo/Doppler and electrical inter-atrial delay (EIAD) derived from IEGM were also analysed. Optimal AV delay was identified by the maximal VTI. In 11 patients (Group 1) the maximal VTI was achieved at the AV delay suggested by the algorithm, in 6 patients (Group 2) after a 25% reduction, and in 6 patients (Group 3) after a 50% reduction. While EIAD was similar among the three groups, MIAD was significantly different ( P < 0.001). MIAD was longer than EIAD in Group 1 ( P = 0.028) and shorter than EIAD in Groups 2 ( P = 0.028) and 3. ( P < 0.001). Mechanical inter-atrial delay was the only independent predictor of the AV interval associated with the best VTI ( R 2 = 0.77; P < 0.001). Conclusion Our results show that MIAD plays the main role in determining the optimal AV delay, thus caution should be taken when optimizing AV by IEGM-based methods.

Amyloidosis comprises a unique group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissue including the heart. Cardiac amyloidosis could be primary a part of systemic acquired amyloidosis, or a result of heredofamilial amyloidosis. Although the infiltration of the heart from different types of amyloid results in restrictive cardiomyopathy that manifests with refractory congestive heart failure and conduction abnormalities, unequivocal identification of the deposited amyloidogenic protein is mandatory in order to avoid misdiagnosis and inappropriate treatment. Recent developments in imaging techniques and extracardiac tissue biopsy have minimized the need for invasive endomyocardial biopsy for amyloidosis. Despite advances in treatment, the prognosis of a patient with amyloidosis is still poor and depends upon the underlying disease, and the type and degree of dysfunction of the involved organs. Thus, early diagnosis is mandatory because patients with advanced disease are usually too ill for intensive therapy. This review outlines current approaches to diagnosis, assessment of disease severity, and treatment of cardiac amyloidosis.

Aims: The aim of this study was to investigate whether alterations in left ventricular (LV) twisting and untwisting motion could be induced by cardiac involvement in patients with immunoglobulin light-chain (AL) systemic amyloidosis. Methods and Results: Forty-five patients with AL amyloidosis and 26 control subjects were evaluated. After standard echocardiographic measurement and two-dimensional (2D) speckle tracking echocardiography, LV rotation at both basal and apical planes, twisting, twisting rate, and longitudinal strain were measured. Tissue Doppler imaging (TDI) derived early diastolic peak velocity at septal mitral annulus (E′) was also evaluated. Twenty-six of 45 patients with systemic amyloidosis were classified as having cardiac amyloidosis (CA) if the mean value of the LV wall thickness was ≥ 12 mm or not (NCA) if this value was not reached. In NCA patients, both LV twist and untwisting rate were increased while they were decreased in CA patients making them similar to the control group. Longitudinal strain was reduced only in CA patients. Impaired relaxation as indicated by E′ values was progressively reduced in the course of the disease. Conclusions: Both twisting and untwisting motions are increased in patients with AL systemic amyloidosis with no evidence of cardiac involvement while they are reduced in patients with evident amyloidosis cardiac involvement. This finding suggests that impaired LV relaxation induces a compensatory mechanism in the early phase of the disease, which fails in more advanced stage when both twisting and untwisting rates are reduced. The increase in LV rotational mechanics could be a marker of subclinical cardiac involvement. (Echocardiography 2010;27:1061-1068)

"Cardiac memory" (CM) refers to a change in repolarization induced by an altered pathway of activation. The effects of biventricular pacing on CM induction have not been investigated.To investigate the development of CM during cardiac resynchronization therapy (CRT) through vectorcardiography (VCG).Eleven patients undergoing CRT were enrolled. VCG was acquired during spontaneous ventricular activation at baseline and during AAI and DDD pacing immediately after and 7, 14, 21 and 60 days after the implantation.At 1-week follow-up, during AAI pacing T vector angles significantly changed (azimuth 23 ± 19°; p = 0.002; elevation 23 ± 27°; p = 0.019) and magnitude significantly increased (baseline 1.13 ± 0.69 mV; 7 days: 1.77 ± 1.27 mV; p = 0.026). T angle changes remained stable throughout the follow-up period while a further significant increase in magnitude was observed at 60 days (2.21 ± 1.50 mV; p = 0.01 vs. baseline and p = 0.04 vs. 7 days). Paced T vector magnitude at implant (2.24 ± 1.25 mV) decreased significantly at 7 days (1.64 ± 1.26 mV; p = 0.030) with a further significant decrease at 60 days (1.40 ± 1.18 mV; p = 0.003 vs. baseline; p = 0.02 vs. 7 days).CRT induces a significant change in T vector magnitude, azimuth, and elevation after resumption of spontaneous ventricular activation after 7 days from implantation. While further changes in T vector angle were not observed, after 2 months of CRT a significant decrease of paced T vector magnitude and a significant increase of spontaneous T vector magnitude were observed.

Using traditional echocardiography, the diagnosis of cardiac amyloidosis (CA) is often only possible in advanced stage when recommended therapies may have adverse effects. The aim of our study was to evaluate whether additional information can be derived from Tissue and strain Doppler imaging (TDI and SDI). Forty patients with systemic amyloidosis and 24 healthy subjects underwent traditional, tissue and strain Doppler echocardiography. Patients were classified having CA if mean wall thickness (mT), was half of the sum septum and posterior wall thickness, wasor =12 mm. The following parameters were evaluated: peak early diastolic velocity (Em) as index of ventricular relaxation, mitral E-wave to Em ratio (E/Em) as index of left ventricular (LV) filling pressure and mean LV strain peak curves (mSt) as global long-axis contraction index. In non cardiac amyloidosis (NCA), both Em and mSt were lower than in age matched controls (p0.01, p0.05, respectively) and higher than in CA (p0.01 and p0.01, respectively). Both Em and mSt were related to mT (p0.001). A significant (p0.01) nonlinear relation was observed between plasma terminal of pro B-natriuretic peptide and mT, Em, E/Em and mSt. TDI and SDI are able to detect amyloid myocardial involvement in such an early stage that cannot be evidenced by using traditional echocardiography.

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, QRSor=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 p0.05). 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/m2 (EDVi) and end systolic volume/m2 (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.

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.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.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 p0.001), 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).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.

Automatic mode switching, enabling the pacemaker to pace at an independent ventricular rate when atrial fibrillation occurs, was introduced to provide protection against rapid ventricular pacing during atrial arrhythmia. This study proposes a technique to test automatic mode switching performance. It is based on a programmable system (Arrhythmia Simulator) generating pulse trains that, when applied to the patient's skin, may interfere with the implanted device simulating supraventricular arrhythmias. The amplitude of the output signals is 5 V and they are delivered through an output resistance of 50 kΩ limiting the current to 100 μA that guarantees no risk of muscle stimulation during the test and meanwhile low noise signals on the surface ECG. The duration of pulses is 20 ms. Pulses delivered by the Arrhythmia Simulator were correctly sensed by the pacemaker's atrial channel, and the detected amplitude was 2 ± 0.8 mV, ranging from 1 to 3 mV. The performance of the system was reliable and safe in every patient despite the use of different pacemaker leads. Automatic mode switching was induced in every patient at every attempt. The pulses delivered by Arrhythmia Simulator didn't alter the quality of ECG tracings making easy and reliable the analysis.

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.

Aims To evaluate the influence of QRS prolongation on the natural history of chronic heart failure (CHF). Methods The results of several studies carried out from 1951 to 2003 were analysed. Results (a) Isolated left bundle branch block (LBBB) is associated with an increased risk of developing cardiovascular disease and increased cardiac mortality; (b) investigations on the effect of right bundle branch block (RBBB) on mortality have yelded conflicting results; (c) the effects of the association of LBBB with left axis deviation (LAD) on further LV function deterioration remain controversial; (d) LBBB in CHF is associated with a significantly higher all-cause and sudden cardiac death mortality. Conclusions LBBB is unequivocably associated with greater disease severity and mortality in patients with CHF.

Atrioventricular delay (AVD) is critical in patients with DDD pacemakers (PM). Echo/Doppler evaluation of AVD providing the longest left ventricular filling time (FT) or the highest cardiac output (CO) is used for AVD optimization. Recently myocardial performance index (MPI) has been shown to improve by optimizing AVD. The aim was to compare the CO, FT, MPI derived optimal AVD, and to analyze systolic and diastolic performance at every optimal AVD. Twenty-five patients, 16 men 68 +/- 11 years, ejection fraction >or= 50%, with a DDD PM for third-degree AV block, without other major cardiomyopathies, underwent echo/Doppler AVD optimization. CO, FT, and MPI derived optimal AVDs were identified as the AVDs providing the highest CO, the longest FT, and the minimum MPI, respectively. Isovolumic contraction and relaxation time (ICT, IRT), ejection time (ET), ICT/ET, and IRT/ET ratios were also evaluated at every optimal AVD. CO, FT, and MPI derived optimal AVDs were significantly different (148 +/- 36 ms, 116 +/- 34 ms, and 127 +/- 33 ms, respectively). ICT/ET was similar at CO, FT, and MPI derived optimal AVD (0.22 +/- 0.10, 0.23 +/- 0.11, and 0.21 +/- 0.10, respectively). IRT/ET ratio was similar at FT and MPI derived optimal AVDs (0.34 +/- 0.15 and 0.33 +/- 0.15, respectively) and significantly shorter (P < 0.02) than at CO derived optimal AVD (0.40 +/- 0.15). Different methods indicate different optimal AVDs. However analysis of systolic and diastolic performance shows that different AVDs result in similar systolic or diastolic performance. At MPI optimized AVD, a high CO combined with the most advantageous conditions of both isovolumic contraction and relaxation phases is achieved.

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 (17224 vs 20724 ms, P

Diagnostic (mapping) and therapeutic (ablation, pacing) advances have provided insightinto atrial depolarization processes and new developments in P wave analysis. Information about interatrial pathwaysis important to the understanding of interatrial conduction delay. A standardized method for P wave analysis isnecessary for the development of a clinical role for management of patients with paroxysmal atrial fibrillationusing signal-averaged P wave analysis and P wave dispersion. Algorithms for predicting localization of ectopic Pwaves may facilitate catheter ablation. P wave changes due to pacing at different atrial sites may be useful forpermanent pacing for prevention of atrial fibrillation. Introduction of these developments into clinical practiceshould allow better prevention and treatment of atrial arrhythmias and could have considerable impact in view oftheir high frequency especially in the older population.

Background Inter-atrial septum pacing may prevent initiation or persistence of atrial fibrillation through suppression of premature beats and regularization of atrial rhythm; prolongation of the coupling interval of the premature beats in the abnormal substrate; and modification of the electrophysiological properties of the substrate. The aim of the present study was to evaluate the rate of progression to permanent atrial fibrillation in patients paced at the inter-atrial septum. Method A total of 70 patients (41 male, 29 female; mean age 72 ± 11 years) with a history of sinus bradycardia and paroxysmal atrial fibrillation (6 ± 10 episodes/month in the 3 months before implantation of a pacemaker) were enrolled. Twenty-six patients were ablated at the atrioventricular junction. Results Sinus rhythm was maintained in 79·8% of the group overall after 50 months. After 36 months, sinus rhythm was maintained in 87·9% of the non-ablated patients and in 61·0% of the ablated patients (P < 0·05). Conclusion These results encourage further evaluation of interatrial septum pacing for prevention of AF. (Eur Heart J Supplements 2001; 3 (Suppl P): P2‐P6)

Objectives: The purpose of this study was to investigate if single lead interatrial septum pacing could be effective in maintaining sinus rhythm in patients in whom restoration of sinus rhythm was only possible for a period of 2–24 hours after one or more previous electrical cardioversions, and in whom a sinus bradycardia was documented before arrhythmia restarted. The two hours limit was chosen because it was considered a sufficient time to implant a dual chamber pacemaker.

Background. There are a variety of approaches to the prevention of atrial fibrillation (AF) with pacing. Aim of this study was to test the safety and feasibility of interatrial septum pacing at the posterior triangle of Koch for AF prevention and to exclude potential arrhythmic effects. Matherial and Methods.Interatrial septum pacing was performed in 34 patients (21 males, 13 females, mean age 69±12 years): 9 without a history and clinical evidence of atrial fibrillation (AF) (6 with sinus bradycardia, 2 with second-degree AV block, and 1 with carotid sinus hypersensitivity) and 25 with sinus bradycardia and paroxysmal atrial fibrillation (PAF) (mean symptomatic episodes/month 6.2±10). In all patients a screw-in bipolar lead was positioned in the interatrial septum superiorly to the coronary sinus. Results.At implant the mean P wave amplitude was 2.5±1.5 mV, the pacing threshold was 1±0.6 V and the impedance was 907±477 Ohm. Mean P wave duration was 118±17 ms in sinus rhythm and 82±15 during interatrial septum pacing (p < 0.001). During a mean follow-up period of 10±7 months, no patients without atrial tachyarrhythmias before implantation experienced AF. During a 9±6 months follow-up we observed only 2 symptomatic arrhythmia recurrences between AF patients (mean symptomatic episodes/month 0.006±0.0022) (p < 0.01 vs before implant period). Conclusions. Our data indicate that interatrial septal pacing is safe and feasible. A significant less incidence of arrhythmic episodes has been observed during follow-up. Further controlled randomized prospective studies are necessary to establish the exact role of this technique respect to conventional or multisite stimulation when patients with paroxysmal AF need to be permanently paced.

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.

Background— 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. Methods and Results— 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). Conclusions— 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.

The importance of right ventricle (RV) dysfunction in AL amyloidosis has been underestimated. This study was designed to comprehensively evaluate RV function and its prognostic role in patients with AL amyloidosis with and without echocardiographic evidence of cardiac involvement. Method and results Fifty-two biopsy-proven AL amyloidosis patients underwent a thorough echocardiographic evaluation. Twenty-seven patients (CA) met the international echocardiographic criteria for cardiac involvement (left ventricular (LV) wall thickness ≥12 mm) and 25 patients had no cardiac amyloidosis features (NCA). Patients were compared with a sex- age-matched control group. Patients and controls underwent traditional, tissue Doppler (TDI), speckle-tracking left and RV echocardiographic evaluation. No difference was observed between groups in RV diastolic diameter, whereas CA patients showed increased RV free wall thickness (P , 0.0001). Compared with controls and NCA patients, traditional echocardiography, TDI, and speckle-tracking evaluation detected significantly (P , 0.0001) depressed RV longitudinal systolic function in CA patients. No difference was observed between groups at Doppler diastolic evaluation, whereas at tricuspidal annulus TDI analysis, CA subject showed significantly lower E ' and Avalues with increased E/Eratio (P , 0.0001). Over a 19 months median follow-up period, 18 patients died. Cox multivariate analysis showed that N-terminal pro-Brain natriuretic peptide and RV longitudinal strain were the strongest death predictor. Conclusion Our data show that in patients with AL amyloidosis, RV involvement develops later than LV amyloid deposition but when it occurs, prognosis dramatically worsens. Moreover RV longitudinal strain was the only echocardiographic pre- dictor of prognosis. We suggest that RV function analysis should be performed routinely as a part of echocardio- graphic evaluation in these patients.

Summary Introduction: Recently, two-dimensional (2D) speckle-tracking echocardiography has enabled assessment of a particular behaviour of left ventricular (LV) motion defined as twisting/untwisting. The aim of our study is to evaluate whether in early stage of hypertension and systemic amyloidosis, subclinical alteration of LV twist and untwist is already present even if no LV hypertrophy is evidenced. Methods: Forty-seven patients with light chain immunoglobulin amyloidosis (AL) entered the study and were classified having cardiac amyloidosis (CA) or not (NCA) if the mean value of LV wall thickness was ≥12 mm or not. Twenty-two consecutive patients with history of arterial essential hypertension (Hyp Group) and no sign of LV hypertrophy were enrolled. A total of 26 asymptomatic healthy subjects, age-matched, were analysed as control group. All three groups of patients and healthy subjects underwent traditional and 2D speckle-tracking echocardiography evaluation. LV diameters, volumes, wall thickness, mass, ejection fraction, E/A and E/E′ ratio were evaluated. Results: Twisting and untwisting rates were significantly increased in NCA and Hyp group when compared with CA and control group. Moreover, despite similar LV mass and diastolic dysfunction degree, untwisting rate peak was significantly delayed in NCA when compared with Hyp group. In patients with CA, untwisting rate delay was similar to patients with NCA. Conclusion: Our results show that amyloidosis and systemic hypertension produce both LV twist and untwist rate enhancement before LV hypertrophy is developed. In patients with amyloidosis irrespectively of LV infiltration degree, a significant LV untwisting rate peak delay occurs suggesting that different aetiology of cardiac involvement could differently affect LV untwisting rate.

Background The beneficial effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) remodeling have been extensively described. Few data are available about the effects of CRT on right ventricular (RV) function and remodeling. Hypothesis We hypothesized that CRT could also induce reverse remodeling in the right ventricle and that RV baseline functional status expressed as tricuspidal annular plane systolic excursion (TAPSE) could affect CRT response. Methods Echocardiographic investigation was performed before and 6 months after CRT. In 192 patients, TAPSE, LV, and RV dimensions with functional parameters and LV dyssynchrony index were evaluated. Results At 6 months' follow-up, 86 patients (45%) were responders to CRT according to at least 15% LV end-systolic volume reduction. Among baseline echocardiographic parameters, responders had significantly lower TAPSE, larger LV volumes, and higher LV dyssynchrony index. In responders, LV volume reduction, ejection fraction increase, and mitral regurgitation improvement were associated with RV dimensions reduction, increased TAPSE, and improved LV dyssynchrony. Receiver operating characteristic curve analysis showed that TAPSE, at 17 mm optimal cutoff, yielded 64% sensitivity and 60% specificity in predicting CRT response; similarly, LV dyssynchrony index, at 41.25 ms optimal cutoff, predicted CRT response with 60% sensitivity and 62% specificity. A subgroup analysis demonstrated that the coexistence of high TAPSE and high dyssynchrony index values increased probability of CRT response. Conclusions Our results show that CRT induces RV and LV reverse remodeling and that CRT patient selection can be improved by simply measuring TAPSE value. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

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.

Aims The majority of tissue Doppler indexes proposed to predict left ventricular (LV) reverse remodelling in cardiac resynchronization therapy (CRT) reflects LV asynchrony as assessed in ejection phase. We evaluated the predictive value of a new strain-imaging parameter reflecting the total amount of time spent by 12 LV segments in contracting after aortic valve closure. Methods and results Fifty-nine patients who fulfilled current treatment recommendations were studied before and 6 months after CRT. Time to tissue Doppler systolic peak velocity (Ts) and time exceeding aortic closure (ExcT) in strain curves were measured in 12 LV segments. Ts standard deviation (Ts-SD) and sum of ExcT of overall 12 LV segments (oExcT) were analysed. After 6 months, responders were defined according to ≥15% LV end-systolic volume reduction. Responders (47%) when compared with non-responders (53%) had significantly higher baseline Ts-SD and oExcT values. Receiver operating characteristic (ROC) curve analysis demonstrated that an optimal cutoff value of 760 ms for oExcT yielded 93.5% sensitivity and 82.8% specificity. For Ts-SD at the cutoff of 32 ms, 82% sensitivity and 39% specificity were obtained. Area under ROC was significantly larger for oExcT than for Ts-SD. Conclusion o-ExcT is able to predict LV reverse remodelling after CRT.

Functional mitral regurgitation (FMR) improvement induced by cardiac resynchronization therapy (CRT) has been related to left ventricular (LV) remodeling reversal and contractility enhancement. The effects induced by the changes of LV synchronicity indexes on FMR severity have not been investigated.In 30 patients with CRT for heart failure (HF) and QRS130 ms, LV function parameters, FMR severity as mitral jet regurgitation/left atrial area ratio (JA/LAA) and standard deviation (SD) of the time to the systolic peak velocity at 6-basal and mid-LV segments as asynchrony indexes were evaluated (echo/tissue Doppler) before and 6 months after implant. At follow-up, 15 patients resulted responders to LV reverse remodeling withor =15% end-systolic volume (ESV) and LV systolic function improvement. Improvement of FMR withor =15% JA/LAA reduction was observed in 19 patients, 7 were nonresponders to LV reverse remodeling. In patients withor =15% JA/LAA reduction a significant decrease of LV asynchrony indexes was observed as compared to patients withoutor =15% JA/LAA reduction in whom LV asynchrony indexes were increased. Reduction of LV mid-segmental asynchrony was the variable most strongly related to JA/LAA reduction (r(2)=0.697, P0.01), with good agreement between observed and predicted values (only 1 patient outside the mean+/-2SD).These data reveal that CRT can reduce FMR irrespective to LV remodeling reversal; this effect is related to LV asynchrony reduction and further support CRT employment in patients with HF and FMR.

Introduction: Right atrial linear lesions (RALL), either alone or in combination with antiarrhythmic drug therapy, may modify the substrate for maintenance of atrial fibrillation (AF). The aim of this prospective randomized study was to determine whether RALL provides additional benefit to right atrial appendage pacing (RAAP) and/or interatrial septum pacing (IASP) and drug therapy in patients with symptomatic paroxysmal AF and sinus bradycardia requiring permanent atrial pacing. Methods and Results: Sixty-four patients (33 men and 31 women, mean age 73 ± 10 years) completed the 6-month follow-up. Patients were randomized to either RALL (n = 33) or non-right atrial linear lesions (NRALL), and then to either IASP (n = 32) or RAAP (n = 32). Fifteen RALL patients were paced at the IAS and 18 at the RAA. Seventeen NRALL patients were paced at the IAS and 14 at the RAA. No statistical difference was observed with regard to the mean atrial tachyarrhythmia (AT) burden between NRALL (84 ± 169 min/day) and RALL patients (202 ± 219 min/day). Mean AT burden was significantly lower in the IASP group (70 ± 150 min/day) than in RAAP group (219 ± 317 min/day; P < 0.016). In the RALL group, the mean AT burden was 99 ± 180 min/day in the IASP patients and 288 ± 372 min/day in the RAAP patients (P < 0.046). In the NRALL group, no statistical difference in the mean AT burden was observed between IASP patients (46 ± 117 min/day) and RAAP patients (130 ± 211 min/day). Conclusion: The results of the present study indicate that RALL did not provide any additional therapeutic benefit to combined antiarrhythmic drug therapy and septal or nonseptal atrial pacing in patients with sinus bradycardia and paroxysmal AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. 733-738, July 2003)

a Cardiology Service, CMSR Veneto Medica, Altavilla Vicentina, Italy b Department of Medical and Surgical Critical Care, University of Florence, Center of the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Disease to Develop Novel Therapies, University of Florence, Italy c Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy d S. Maria agli Ulivi Center, Fondazione Don Carlo Gnocchi, Onlus, IRCCS, Florence, Italy

Background: The extracellular matrix tissue of the myocardium importantly contributes to left ventricular (LV) performance. Inherited connective tissue disorders related to the FBN1 gene could involve cardiac interstitium resulting in functional abnormalities. Hypothesis: To disclose a primary involvement of myocardium, LV function was studied in 28 patients affected by Marfan syndrome or Marfan‐related disorders: 20 Marfan and 8 MASS (Mitral valve prolapse, Myopia, Aortic dilatation, Skeletal involvement, Skin striae) and in 28 healthy, age and gender‐matched controls. No valvular regurgitation or any other cardiac alterations were present. Methods: Echocardiographic study was performed to investigate LV systolic and diastolic function. Results: No statistically significant differences were observed between patients and the control group in LV dimensions, systolic function parameters (ejection and shortening fraction), and some diastolic function parameters (E peak, A peak, E/A), while statistically significant differences were found between patients and the control group in LV mass (128.7 ± 46.6 vs. 83.7 ± 14.5 g/m(2), p < 0.008), in isovolumic relaxation time (102.0 ± 24.0 vs. 80.1 ± 11.2 ms, p

Optimal management of atrial arrhythmias with dual chamber pacemakers requires proper performance of automatic mode switching (AMS). The aim of this study was to develop a reliable technique to test the AMS function by using an external electronic device capable of mimicking the occurrence of supraventricular arrhythmias (Supraventricular Arrhythmia Simulator [SAS]). The SAS delivers low voltage pulse trains (200 mV, 20 ms) through two skin electrodes. Each pulse train lasts 15 seconds and starts synchronously with a pacing pulse of the implanted pacemaker to avoid interference from the operator. The pulse train rate is set at 350, 250, and 160 beats/min to simulate AF, atrial flutter, and atrial tachycardia (AT), respectively. Thirty-five patients implanted with Vitatron pacemakers, whose AMS system has been previously validated, were enrolled. Atrial and ventricular sensing were programmed in unipolar mode at 0.5 mV and in bipolar mode at > 2 mV, respectively. All pulses from the SAS were detected by the atrial channel at an amplitude ranging from 1 to 3 mV. The test proved to be safe and reliable at rest and during exercise. AMS occurred immediately at onset or at offset of atrial arrhythmias, and no adverse interference on pacemaker function was seen from the SAS. In conclusion, the described technique and the SAS are safe and reliable for patient and pacemaker function and can be proposed as a useful method to verify proper performance of AMS function irrespective of the type of implanted devices.

PADELETTI, et al.: Atrioventricular Interval Optimization in the Right Atrial Appendage and Interatrial Septum Pacing: A Comparison Between ECHC and Peak Endocardial Acceleration. Interatrial septum pacing (IASP) reduces interatrial conduction time and consequently may interfere with atrioventricular delay (AVD) optimization. We studied 14 patients with an implanted BEST Living system device able to measure peak endocardial acceleration (PEA) signal. The aims of our study were to compare the (1) optimal AVD (OAVD) in right atrial appendage pacing (RAAP) and IASP, and (2) OAVD derived by the PEA signal versus OAVD derived by Echo/Doppler evaluation of the left ventricular filling time (LVFT) and cardiac output (CO). Measurements were performed in DDD VDD modes Eight patients (group A) had RAAP and six patients (group B) had IASP. In group A, OAVD measured by LVFT, CO, and PEA was 185 ± 23 ms, 177 ± 19 ms, and 192 ± 23 ms in DDD and 147 ± 19 ms, 135 ± 27 ms, and 146 ± 20 ms in VDD, respectively. OAVD measured by LVFT, CO, and PEA was significantly longer in DDD mode than in VDD (P < 0.01, P < 0.01, P < 0.001). In group B, OAVD measured by LVFT, CO, and PEA was 116 ± 19 ms, 113 ± 10 ms, and 130 ± 30ms in DDD and 106 ± 16 ms, 96 ± 15 ms, and 108 ± 26 ms in VDD, respectively. No statistical differences were observed between DDD and VDD. Significant correlations between OAVDs PEA derived and OAVDs LVFT and CO derived were observed (r = 0.71, r = 0.69, respectively). When new techniques of atrial stimulation, as IASP, are used an OAVD shorter and similar in VDD and DDD has to be considered. The BEST Living system could provide a valid method to ensure, in every moment, the exact required OAVD to maximize atrial contribution to CO.

For many years implantable devices for cardiac pacing applications have been developed with the main aim of treating AV block and sinus node dysfunction. With the introduction of rate-responsive pacing in 1983, different kinds of sensors have been developed, clinically validated and introduced into the clinical practice for driving rate adaptive pacemakers.

Biventricular pacing has been proposed to resynchronize ventricular contraction in patients with congestive heart failure (CHF) and interventricular conduction delay. However, the sudden death rate is still high despite the improvement in cardiac performance. Devices combining biventricular pacing with implantable cardioverter defibrillator (ICD) backup are now under clinical investigation to demonstrate whether they can decrease sudden death. From the first implant of an ICD with biventricular transvenous pacing on August 1998 to April 2000, 96 patients underwent such implants: 67 (70%) received pacemakers alone and 29 (30%), who had class I ICD indications, received combined pacemaker/ICD systems. During a mean follow-up of 283 +/- 170 days, 13 (14%) patients died: 5 of 29 (17%) in the ICD group and 8 of 67 (12%) in the pacemaker group. A total of 15 patients (52%) had ICD shocks and 6 patients (21%) had 113 episodes of ventricular tachyarrhythmias, of which 96 (85%) were converted to sinus rhythm with antitachypacing. The echocardiograms showed a narrowing of the delay between the onset of right and left ventricular outflow from 40 +/- 37 msec to 17 +/- 16 msec (p = 0.03) and a reduction of the mitral regurgitation area from 7 +/- 3.8 cm2 to 5 +/- 4 cm2 (p = 0.04) at 3 months. Functional class improved from 2.8 +/- 0.7 to 1.6 +/- 0.5 (p0.001) 3 months after implant. Thus, ischemic patients with reduced left ventricular ejection fraction and ventricular tachyarrhythmias seem good candidates for biventricular pacing with ICD backup. The sudden death risk for those with idiopathic dilated cardiomyopathy, however, is difficult to stratify, and the choice of ICD backup has to be considered on the basis of patient safety, as well as of costs.

Signal-averaged P wave of 42 patients with lone paroxysmal atrial fibrillation (PAF) and 29 normal subjects (N) were recorded, using three orthogonal leads and analyzed in the time and frequency (entire P wave or a 100-ms segment ranging from 75 ms before to 25 ms after the end of P wave) domains. PAFs were divided into a group of 12 having > or = 2 attacks a month (HF) and a group of 30 having < or = 2 attacks a year (LF). Statistically significant differences were absent with regard to ages of PAF and N; ages of HF, LF, and N at the time of signal-averaged ECG; ages of HF and LF at the time of the first arrhythmic episode; and elapsed times from the first episode. Length of P wave and some frequency-domain parameters were found to be significantly correlated with age. PAF showed a significantly longer duration of P wave in the frontal plane using the time-domain analysis. Frequency analysis was found to be useful in evaluating the influence of attack frequency. HF showed significantly higher values of some frequency-domain parameters than LF and N, while the three groups did not differ for time-domain analysis. P wave duration and frequency content of the three orthogonal leads proved to be significantly different in PAF and N. Right and left atrial echocardiographic dimensions proved to be higher (even if within normal limits) in HF than in LF and N. Results suggest that frequency analysis should be performed on the entire P wave.

The purpose of this study was to evaluate the wavelength index (WLI) at three atrial sites in a group of 23 patients with recurrent episodes of lone paroxysmal atrial fibrillation (LPAF) and a control group (n = 20). All patients underwent programmed atrial stimulation (paced cycle length = 600 ms) at high, medium, and low lateral right atrial wall. P wave duration, sinus cycle length, and corrected sinus node recovery time were not significantly different between the two study groups. WLI was calculated according to the following formulas: atrial effective refractory period (AERP)/duration of atrial extrastimulus electrogram (A2) or AERP/A2 + atrial latency; and atrial functional refractory period (AFRP)/A2. WLI was significantly shorter in LPAF than in the control group at each of the paced atrial sites independently of the formula used. Duration of premature atrial electrogram appeared to play the major role in determining the difference in WLI between patients with paroxysmal atrial fibrillation and the control group.

In a 26-year-old man, an echocardiographic examination was performed for recurrent episodes of syncope. He had no familial history of cardiovascular diseases or sudden cardiac death. Traditional standard 2-dimensional (2D) echocardiography showed left ventricular (LV) dilatation with prominent trabeculations and diffuse contractility impairment (ejection fraction, 0.35) (Figure 1). Although the presence of isolated ventricular noncompaction of the myocardium (IVNC) was suspected, such findings did not fulfill the established criteria for the diagnosis as proposed by Jenni et al. 1 When transthoracic real-time 3-dimensional echocardiography (RT3DE) was performed with a model sonography system (IE33RD; Philips Medical Systems, Bothell, WA), a thickened myocardium with extensive trabeculations of both ventricles, especially in the LV apical and midventricular areas of both the inferior and lateral segments, clearly appeared, and the typical 2-layered structure of the myocardium was disclosed, with a thin, compacted outer band and a much thicker, noncompacted inner layer. The maximal end-systolic ratio of the noncompacted endocardial layer to the compacted myocardium was greater than 2 (Figure 2A). The 3-dimensional (3D) color images were able to denote the deep intertrabecular recess flow (Figure 2B). Thus, all the proposed diagnostic criteria for IVNC were fulfilled. Cardiac nuclear magnetic resonance (NMR) imaging subsequently performed confirmed the findings with the presence of extensive trabeculations and deep intratrabecular recesses involving the right ventricular apex and LV lateral and posterior walls, as shown on RT3DE (Figure 3).