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Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the gene encoding fibrillin-1 ( FBN1 ), a matrix component of microfibrils. Dural ectasia, i.e. enlargement of the neural canal mainly located in the lower lumbar and sacral region, frequently occurs in Marfan patients. The aim of our study was to investigate the role of dural ectasia in raising the diagnosis of Marfan syndrome and its association with FBN1 mutations. We studied 40 unrelated patients suspected for MFS, who underwent magnetic resonance imaging searching for dural ectasia. In all of them FBN1 gene analysis was also performed. Thirty-seven patients resulted affected by Marfan syndrome according to the '96 Ghent criteria; in 30 of them the diagnosis was confirmed when revaluated by the recently revised criteria (2010). Thirty-six patients resulted positive for dural ectasia. The degree of dural ectasia was grade 1 in 19 patients, grade 2 in 11 patients, and grade 3 in 6 patients. In 7 (24%) patients, the presence of dural ectasia allowed to reach a positive score for systemic feature criterion. Twenty-four patients carried an FBN1 mutation, that were represented by 13 missense (54%), and 11 (46%) mutations generating a premature termination codon (PTC, frameshifts and stop codons). No mutation was detected in the remaining 16 (6 patients with MFS and 10 with related disorders according to revised Ghent criteria). The prevalence of severe (grade 2 and grade 3) involvement of dura mater was higher in patients harbouring premature termination codon (PTC) mutations than those carrying missense-mutations (8/11 vs 2/13, P = 0.0111). Our data emphasizes the importance of dural ectasia screening to reach the diagnosis of Marfan syndrome especially when it is uncertain and indicates an association between PTC mutations and severe dural ectasia in Marfan patients.

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.

Background: The management of implantable cardioverter defibrillators (ICDs) affected by advisories, which often include generator replacement, is complex and the risk of device failure needs to be carefully assessed for each patient. Methods: We analyzed the response to the advisory communication in the Italian centers involved in the recall for the Prizm 1861 and Renewal (Boston Scientific–formerly Guidant—St. Paul, MN, USA) communication. Results: One hundred and thirty-nine of 843 Prizm (16.5%) and 458 of 2,342 Renewal devices (19.6%) were explanted. The total incidence over a 4-year time frame of the failure event was equal to zero of 710 (0%) for Prizm ICDs and eight of 2,342 (0.34%) for Renewal ICDs. A limited percentage of devices affected by recall were definitely explanted following the indications stated by the advisory. The failure rates that resulted from analysis of our data (0% for Prizm and 0.34% for Renewal) were inferior to those already found or projected along the device lifetime globally, as reported in the most recent Company Product Performance Report (0.72% for Prizm and 1.83% for Renewal). Conclusions: In absence of underestimation of the events, a lower incidence than expected could resize the dimension of the problem, justifying the concept of a more frequent follow-up of patient with respect to the choice of an immediate device explant. (PACE 2011; 34:998–1002)

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.

Marfan syndrome, a human disease involving cardiovascular and skeletal apparatuses and ocular and central nervous systems, is associated to mutations in FBN1 gene; heterozygous mutations in TGFBR2 and TGFBR1 genes were found associated to MFS type 2, characterized by the presence of skeletal and cardiovascular major criteria and absence of eye major criterion. We screened the TGFBR1 gene in 46 Marfan patients in whom mutations in FBN1 and TGFBR2 genes were excluded and the analysis of Ex1 was extended to additional 114 Marfan patients and 237 controls. We detected two potentially pathological sequence variants: the TGFBR1 6Ala allele whose frequency was higher in the group of Marfan patients (0.13) than in the controls (0.08) (p=0.013; OR=1.69) and an insertion of 20 nucleotides in the 5'UTR that turned out to be a familial silent rare polymorphism. We hypothesize that TGFBR1 sequence variants may act not only as major, but also as low penetrance alleles of the clinical phenotype in Marfan syndrome.

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)

Marfan syndrome (MFS) is a multisystemic disease associated with mutations in the fibrillin-1 gene. Most of the reported mutations are missense substitutions mainly affecting the epidermal growth factor (EGF)-like protein domain structure and the calcium-binding (cb) site. The aim of our study was to investigate the correlation between fibrillin-1 frameshift mutations and the clinical phenotype in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic mutation was found. We detected novel mutations causing premature termination codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the skeletal and cardiovascular systems. Interestingly, we noticed that, while mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the mutation in exon 40 (cbEGF #24 domain) is more severe and causes major cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is noteworthy that the degree of the severity in the phenotype of one of our patients and another from the literature carrying a mutation in exon 41 could be explained with alterations in mRNA expression.

0.91–1.31 1.11 0.77–1.60 Metabolic syndrome — NCEP 1.16 0.99–1.35 1.56* 1.06–2.29 1.14 0.95–1.37 1.20 0.83–1.74 Abdominal obesity — IDF 1.27** 1.08–1.50 1.25 0.85–1.84 0.96 0.79–1.17 1.11 0.75–1.64 Abdominal obesity — NCEP 1.18* 1.01–1.39 1.26 0.86–1.85 1.20 0.99–1.44 0.95 0.65–1.39 Hypertension 1.35*** 1.14–1.59 1.21 0.82–1.80 1.15 0.94–1.41 1.02 0.69–1.53 Low high-density lipoprotein 0.92 0.74–1.14 1.98* 1.10–3.57 0.89 0.69–1.15 1.00 0.60–1.66 Elevated triglycerides 0.75 ** 0.61–0.92 0.92 0.57–1.47 0.93 0.73–1.17 1.31 0.83–2.06 Insulin resistance TG/HDL 0.87 0.75–1.02 1.55* 1.05–2.29 0.90 0.74–1.09 0.88 0.60–1.28 Hyperglycemia 1.34*** 1.14–1.57 1.38 0.95–2.01 1.13 0.94–1.36 1.00 0.69–1.46 Women Metabolic syndrome — IDF 1.52*** 1.34–1.75 1.44* 1.07–1.94 1.15* 1.00–1 .33 0.74 0.53–1.05 Metabolic syndrome — NCEP 1.54*** 1.35–1.77 1.35* 1.00–1.82 1.26** 1.09–1.45 0.86 0.61–1.22 Abdominal obesity — IDF 1.47*** 1.25–1.73 0.82 0.57–1.17 1.23* 1.03–1.46 0.73 0.51–1.06 Abdominal obesity — NCEP 1.56*** 1.36–1.78 1.00 0.82–1.22 1.34*** 1.16–1.56 0.88 0.63–1.23 Hypertension 2.15*** 1.84–2.52 1.23 0.90–1.68 1.19* 1.02–1.39 0.90 0.64–1.27 Low high-density lipoprotein 1.12 0.96–1.31 1.59* 1.11–2.27 0.98 0.83–1.16 1.01 0.68–1.50 Elevated triglycerides 1.08 0.89–1.30 0.94 0.62–1.42 1.01 0.82–1.24 1.32 0.83–2.11 Insulin resistance TG/HDL 1.15* 1.00–1.34 1.60** 1.14–2.26 1.04 0.89–1.22 0.93 0.63–1.37 Hyperglycemia 1.45*** 1.27–1.65 1.48** 1.11–1.98 1.16* 1.01–1.33 1.01 0.72–1.41

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 Thromboembolism occurs in 0.4% to 2% of the subjects undergoing radiofrequency ablation (RFA), but its mechanisms remain unclear. Our aim was to evaluate several parameters of the hemostatic system in relation to the electrophysiologic procedure. Methods Thirty consecutive patients were enrolled in the study. Fifteen underwent electrophysiologic study and 15 underwent radiofrequency ablation. Before the ablation procedure, all subjects were given an intravenous heparin bolus (2500 IU). Blood samples were drawn immediately before, at the end of, and 24 hours after the procedures. Spontaneous platelet aggregation in whole blood and in platelet-rich plasma, markers of clotting activation (prothrombin fragment 1+2 and the thrombin-antithrombin complex) and the fibrinolytic system (plasminogen activator inhibitor and D -dimer) levels were evaluated. Results At the end of the procedure, spontaneous platelet aggregation in whole blood, prothrombin fragment 1+2, thrombin-antithrombin complex, and D -dimer levels increased significantly in all patients. The hemostatic changes were more marked after RFA than after electrophysiology. Spontaneous aggregation in whole blood, prothrombin fragment 1+2, and thrombin-antithrombin complex levels at 24 hours after the procedure were similar to those observed before the procedure in both groups; D -dimer levels were still elevated with respect to preprocedure levels, with a trend toward higher levels in patients undergoing RFA rather than electrophysiology. A significantly more marked activation of coagulation (prothrombin fragment 1+2, P < .005) was found in patients in whom the mean duration of energy application was higher than 23.5 seconds. Conclusions Our data suggest that antithrombotic prevention with a prolonged administration of heparin and/or the association of antiplatelet agents should be considered in patients undergoing RFA. (Am Heart J 1999;138:128-32.)

High resolution P wave signal-averaging from the surface electrocardiogram has been extensively used to identify patients prone to atrial arrhythmias, especially atrial ~brillation (AF) [1]. Yet, despite the considerable body of research the signal-averaged P wave has not been yet accepted into clinical practice. However, since the last review on this journal [1], several studies devoted to P wave signal-averaging have been published. New attempts to re~ne this technique and other studies concerning its clinical applications have been done. In particular, adoption of new parameters [2,3] and a more sophisticated utilization of the older measurements [4,5] have led to a more comprehensive knowledge of the potential utilizations of this technique. Other authors have de~ned its reproducibility [6,7] and also begun to investigate the relative utility of different analysis methods [8–10] in an attempt to introduce some degree of standardization between diverse averaging systems. These initial data suggest that the signal averaged P wave might ultimately ~nd a clinical role, not only as a diagnostic test for AF or as a predictor of its occurrence, but also as an adjunct to its management and an investigational tool that helps to advance our understanding of the arrhythmia in humans. Thus, this review is devoted not only to inform about emerging technical improvements but also to delineate the possible new indications of this test in clinical settings. To this end papers published after the previous review [1] have been utilized almost exclusively.

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.

The Seattle Heart Failure Model (SHFM) is a multimarker risk assessment tool able to predict outcome in heart failure (HF) patients.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.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 (P0.001). 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.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.

The management of implantable cardioverter defibrillators (ICDs) affected by advisories, which often include generator replacement, is complex and the risk of device failure needs to be carefully assessed for each patient.We analyzed the response to the advisory communication in the Italian centers involved in the recall for the Prizm 1861 and Renewal (Boston Scientific-formerly Guidant-St. Paul, MN, USA) communication.One hundred and thirty-nine of 843 Prizm (16.5%) and 458 of 2,342 Renewal devices (19.6%) were explanted. The total incidence over a 4-year time frame of the failure event was equal to zero of 710 (0%) for Prizm ICDs and eight of 2,342 (0.34%) for Renewal ICDs. A limited percentage of devices affected by recall were definitely explanted following the indications stated by the advisory. The failure rates that resulted from analysis of our data (0% for Prizm and 0.34% for Renewal) were inferior to those already found or projected along the device lifetime globally, as reported in the most recent Company Product Performance Report (0.72% for Prizm and 1.83% for Renewal).In absence of underestimation of the events, a lower incidence than expected could resize the dimension of the problem, justifying the concept of a more frequent follow-up of patient with respect to the choice of an immediate device explant.

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.

Current guidelines for cardiac resynchronization therapy (CRT) include electrical but not mechanical dyssynchrony assessment. Our study aims to investigate the effects of isolated or combined mechanical and electrical dyssynchrony, according, respectively, to a standard deviation of tissue Doppler imaging (TDI) derived time to systolic peak ≥32.6 ms and to a QRS duration ≥120 ms, in predicting CRT reverse remodeling.One hundred ninety-two CRT patients were studied. All patients underwent a complete standard and TDI echocardiography examination before and 6 months after CRT. According to baseline evaluation patients were divided into Group 1, patients with isolated electrical dyssynchrony (QRS ≥ 120 ms, TS-SD32.6), Group 2, patients with isolated mechanical dyssynchrony (QRS120 ms, TS-SD ≥ 32.6) and Group 3, patients with combined electrical and mechanical dyssynchrony (QRS ≥ 120 ms, TS-SD ≥ 32.6). Patients were considered CRT responders according to ≥15 left ventricular end-systolic volume (LVESV) reduction at follow-up (FU).At FU, 86 (45%) patients were responders. The highest CRT response rate was observed in Group 3 (62/119, 52%, P0.001 vs. Group 1). No significant differences in response rate were observed between Group 1 (13/47, 27%) and Group 2 (11/26, 42%). In Group1, CRT did not induce any significant change in LV end-diastolic volume (LVEDV), LVESV, LV ejection fraction (LVEF), myocardial performance index (MPI), while in Group 2, LVEF (P0.001) and MPI (P0.05) were improved. In Group 3, LVEDV, LVESV, LVEF, MPI were significantly improved (P0.0001 for all).Our data demonstrate that the highest CRT response rate can be achieved by combining traditional QRS criterion and a currently used echocardiographic dyssynchrony parameter.

The effect of cardiac resynchronization therapy (CRT) on systemic inflammation and neurohormonal alterations associated with heart failure is not well characterized. Accordingly, we aimed to assess the long term effects of CRT on systemic inflammation and neurohormonal factors in heart failure patients.In 47 HF patients (NYHA III-IV) we evaluated, at baseline and after one year of CRT: TNF-alpha, TNF soluble receptors (sTNFR1 and sTNFR2), insulin-like growth factor-1alpha (IGF-1alpha), adiponectin, norepinephrine, pro-atrial natriuretic peptide (pro-ANP), N-terminal-pro-brain natriuretic peptide (NT-proBNP) and angiotensin II, NYHA functional class, quality of life (the Minnesota Living with Heart Failure questionnaire), a 6-minute walk test and an echocardiogram. Long-term CRT decreased activation of renin-angiotensin system (RAS) only in patients with reverse remodelling. It failed to prevent a decline in adiponectin levels, regardless of reverse remodelling. NT-proBNP remained unchanged in patients with reverse remodelling, whereas its levels increased in those without reverse remodelling. IGF-1alpha increased with CRT, whereas CRT had no effect on pro-ANP and inflammatory markers.Long-term CRT is associated with decreased RAS activation and stabilization of NT-proBNP in heart failure patients with reverse remodelling. Long-term CRT, with or without reverse remodelling, does not affect systemic inflammation and fails to prevent a decline in adiponectin.

Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission. Major clinical manifestations affect cardiovascular and skeletal apparatuses and ocular and central nervous systems. We analyzed FBN1 gene in 99 patients referred to our Center for Marfan Syndrome and Related Disorders (University of Florence, Florence, Italy): 85 were affected by MFS and 14 by other fibrillinopathies type I. We identified mutations in 80 patients. Among the 77 different mutational events, 46 had not been previously reported. They are represented by 49 missense (61%), 1 silent (1%), 13 nonsense (16%), 6 donor splice site mutations (8%), 8 small deletions (10%), and 3 small duplications (4%). The majority of missense mutations were within the calcium-binding epidermal growth factor-like domains. We found preferential associations between The Cys-missense mutations and ectopia lentis and premature termination codon mutations and skeletal manifestations. In contrast to what reported in literature, the cardiovascular system is severely affected also in patients carrying mutations in exons 1-10 and 59-65. In conclusion, we were able to detect FBN1 mutations in 88% of patients with MFS and in 36% of patients with other fibrillinopathies type I, confirming that FBN1 mutations are good predictors of classic MFS.

Although optimization of atrioventricular and interventricular delays has been demonstrated to improve hemodynamics in patients with cardiac resynchronization therapy (CRT), the required time-consuming procedure discourages its use in clinical practice. Recently, a new method for CRT optimization based on the intracardiac electrogram (IEGM) detected by the implanted leads, has been developed. We evaluated the effectiveness of this method in improving left ventricular (LV) asynchrony and performance using real-time 3D echocardiography (RT3DE).Twenty patients with CRT were prospectively studied. RT3DE was performed before and after IEGM optimization. The standard deviation of the time to the regional LV minimum systolic volume (Tmsv) for all 16 segments (Tmsv 16-SD), six basal and six mid segments (Tmsv 12-SD), and the six basal segments (Tmsv 6-SD) were assessed as a asynchrony indexes. LV end-diastolic and end-systolic volumes (EDV, ESV), stroke volume (SV), ejection fraction (EF), myocardial performance index (MPI), ejection time (ET), and filling time (FT), corrected by R-R interval, were also evaluated. After IEGM optimization, as compared with baseline Tmsv 12-SD and Tmsv 16-SD decreased (P = 0.01, P0.001, respectively), EF and SV improved (P0.001, P = 0.01 respectively), FT/RR and ET/RR increased (P = 0.02 for both), and MPI improved (P0.001). Tmsv 6-SD, EDV and ESV did not change.A simple IEGM-based method of CRT optimization decreased LV dyssynchrony and improved systolic function.

Homocystinuria is a metabolic disorder associated with defects in genes encoding for methionine metabolism enzymes. Vascular and connective tissue manifestations such as deep venous thrombosis, ectopia lentis and skeletal alterations are the major clinical features. We investigated the clinical manifestations of 5 Italian homocystinuric patients, performed mutation screening analysis on cystationine beta-synthase (CBS) gene and searched for genotype/phenotype correlations. We detected mild cardiovascular and skin connective tissue stigmas in these patients, never reported in homocystinuric patients before. We found 1 novel and 7 known mutations. Our patients carried no other mutation associated with venous thrombosis. Our data stress the importance of extending the clinical investigation for connective tissue manifestations in homocystinuric patients to all the organs/systems involved in Marfan syndrome, also suggesting long term follow-ups for cardiovascular manifestations.

Ectopia lentis (EL) and Marfan syndrome (MFS) are considered two distinct clinical entities. We performed genetic and clinical studies to investigate whether EL is actually distinct from MFS or if it is a mild phenotypic expression of it.Seven patients with EL were followed for 5-10 years. Mutation screening analysis of the 65 exons of FBN1 was performed by polymerase chain reaction (PCR) amplification of genomic DNA, denaturing high pressure liquid chromatography analysis, and direct sequencing of heteroduplexes.Yearly examinations during the 10 years of follow-up allowed the detection of a late onset of dural ectasia in six out of seven patients (age range: 32-64 years versus 8-55 years in MFS previously reported). We also detected the onset of mild thoracic aortic dilatation in a sporadic case (age 45). Six out of seven index cases of EL turned out to be mild forms of Marfan syndrome with possible late cardiovascular involvement as detected in one case. Four novel missense mutations and one known splicing mutation were detected in five out of seven (71%) patients. Their localization confirmed the presence of a first hot spot within exons 1-15 and suggested the presence of a second one between exons 31-39.The presence of a second major criterion in six EL patients shifted the clinical diagnosis from EL to MFS. These data demonstrate that some cases, which are initially diagnosed as EL, turn out to be mild Marfan patients. A clinical cardiovascular follow-up is therefore highly recommended for all EL patients since they may develop thoracic aortic aneurysm (TAA) or dissection later in life. Also magnetic resonance imaging (MRI) for dural ectasia (DE) should be performed in a complete follow up for a MFS diagnosis.

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.

Marfan syndrome is an inherited connective tissue disorder with an autosomic dominant transmission. The prevalence is 1:5000-10 000 and the clinical major criteria involve the skeletal and ocular apparatus and the cardiovascular and central nervous system. The main cause of morbidity is represented by the thoracic aortic dissection/aneurysm that is responsible for 80% of the deaths.We performed a clinical study on 227 patients enrolled at our Clinical and Research Marfan and Related Disorders Center. The aim of this study was to describe the prevalence of cardiovascular manifestation in this cohort of patients.Aortic dilation was present in 172 patients (75.8%), mitral valve prolapse in 179 (78.9%). Aortic insufficiency was present in 83 patients (36.6%), mitral insufficiency in 165 (72.7%). When analyzed separately, in10-year and40-year patients aortic dilation was more prevalent than mitral valve prolapse. Three patients presented with interatrial septal defect, 4 aortic bicuspid valve; 23 had a history of ventricular and supraventricular arrhythmias, and in 2 patients an implantable cardioverter device had been implanted. Fifty-seven patients were treated with beta-blockers and 28 had been operated for aortic aneurysmal dilation.In Marfan syndrome mitral valve prolapse and aortic dilation are the main cardiovascular manifestations, interatrial septal defect and aortic bicuspid valve had the same prevalence than in subjects without Marfan syndrome. These data refer to our first patient evaluation; further studies are needed to evaluate the progression and the natural history of cardiovascular manifestations in Marfan syndrome.

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.

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.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.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% (P0.03) and LVEDVI and LVESVI decreased from 159 +/- 70 mL to 135 +/- 68 mL (P0.02) and from 127 +/- 67 mL to 104 +/- 65 mL (P0.01), respectively.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.

Aims The aim of this study was to evaluate (1) homocysteinemia and the prevalence of the C677T MTHFR polymorphism in Marfan patients and (2) whether the severity of cardiovascular manifestations is associated with homocysteinemia and/or C677T polymorphism. Methods and results We studied 107 patients subdivided into three subgroups based on the severity of cardiovascular manifestations: (A) no involvement ( n =4); (B) mild involvement ( n =45); (C) aortic dilatation or aortic dissection ( n =58), and 189 controls. Total homocysteine (tHcy) was significantly higher in subgroup C than in subgroup B. In subgroup C patients with dissection tHcy was higher than in those without dissection. In subgroup C the prevalence of 677T homozygotes was higher, but not significantly, than in the subgroup B. In patients with dissection the prevalence of 677T homozygotes was significantly higher than in those without dissection and than in subgroup B. In the logistic regression analysis, severe cardiovascular manifestations and aortic dissection in Marfan patients were associated with tHcy plasma levels. Conclusions Our data indicate an association between the severity of the cardiovascular manifestations, in particular aortic dissection, and elevated tHcy levels. This suggests an important role for tHcy in determining phenotypic variability in Marfan patients and provides further evidence for the association of homocysteinemia with the damage of the vascular system.

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