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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. 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. 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. 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.

Implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have been introduced during the recent years to improve survival, decrease hospital readmissions and mortality, and to improve functional status and quality of life for patients with heart failure and left ventricular systolic dysfunction (LVSD). Studies which evaluated the use of CRT or ICD alone or compared CRT with CRT-ICD in patients with heart failure and LVSD are listed in this article. The results obtained are already influencing clinical practice in the US, where it has been estimated that 90% of patients receiving a CRT device now are being implanted with an ICD component. However, it is still today debated whether patients with LVSD and heart failure should be routinely offered a CRT-ICD. In fact, there are some issues that still should be solved before to establish indication for CRT-D in all heart failure patients with an indication for CRT: 1) a non complete agreement among the different societies which wrote recommendations for guidelines (a comparative table is reported); 2) a better identification of implantable patients and an amelioration of utilized devices; 3) economic and ethical ramifications of this therapy. Anyway still now the crucial question is: ''Can resynchronization be done in isolation or must be accompanied by an ICD device?''. To answer to this question we can only express which is, in our opinion, the actual position of many physicians who work in the field of pacing and electrophysiology: ''The lesson to be learned is that we still can not predict surely which patient will die of sudden death. Until a method of identifying the high risk patients can be developed, the safest strategy should be to advise a combined ICD-CRT device for patients with indication for CRT''.

Cardiac resynchronization therapy (CRT) reduces the severity of functional mitral regurgitation (FMR) in patients with heart failure and left bundle branch block. Our hypothesis was that the induction of a more synchronous mitral valve anulus contraction can be a mechanism of FMR reduction in CRT patients.An echo tissue Doppler imaging (TDI) examination was performed at baseline and 6 months after biventricular pacing system implant in 30 patients (4 females and 26 males, 74.1+/-6.1 years) with dilatative or ischemic chronic heart failure, NYHA class = orIII, ejection fraction (EF) = or35% and QRS = or140 ms. EF, Myocardial Performance Index (MPI), left end-diastolic and systolic volumes (LVEDV, LVESV), mitral regurgitation jet area/left atrial area (JA/LAA), effective regurgitant orifice area (EROA), mitral anulus contraction (MAC) were evaluated. Using TDI, at the 6 left ventricle (LV) basal segments the time to the peak myocardial sustained systolic velocity (Ts) and the standard deviation (SD) of TS were evaluated.At 6 months follow-up NYHA class, EF, MPI were significantly improved, LV volumes were reduced. FMR degree, evaluated both as JA/LAA and EROA, was significantly reduced. This effect was associated with the 6 basal segments resynchronization and with a more effective annular contraction.Our data show that CRT by resynchronizing left ventricular basal segments produces a more effective mitral valve annulus contraction and contributes to FMR improvement. Further studies need to evaluate if this could be taken into account as new therapeutic perspective of functional mitral valve regurgitation.

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.

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.Alternative atrial pacing techniques have been demonstrated to be successful in preventing recurrences of atrial fibrillation (AF) in patients with sinus bradycardia. Excluding the AF occurring after only a few sinus beats, at 24 hours from electrical cardioversion an early restart of chronic AF has been reported in 12% to 17% of the patients.After sinus rhythm was restored by internal electrical cardioversion, 17 patients, 7 ablated at the AV junction, underwent a dual chamber rate response (DDDR) pacemaker implantation with a screw-in atrial lead placed in the interatrial septum.After a follow-up period of 17+/-5 months (range 12 to 27 months) persistence of sinus rhythm was observed in 11 patients (65%). Six patients (35%) had recurrences of paroxysmal attacks, while five (30%) were totally free of AF. Recurrence of chronic AF was observed in six cases (35%) after 2 days-12 months from implantation. No dislodgements of the atrial lead and no complications were observed at implantation and during follow-up.Interatrial septum pacing is a safe and feasible technique with a satisfying success rate (65%) in long-term maintaining sinus rhythm in previously unsuccessfully cardioverted patients.

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.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.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 (p0.001). 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) (p0.01 vs before implant period).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.

To evaluate the existence of a peculiar atrial electrophysiologic substrate, we studied 18 patients with asymptomatic Wolff-Parkinson-White (WPW) syndrome. These patients were compared with 10 age-matched normal subjects (N). Effective and functional refractory periods were determined at two right atrial sites (high and low in the lateral wall), during atrial pacing (100 min-1) and at twice diastolic threshold. Disperson (D) of effective (ERP) and functional (FRP) refractoriness was evaluated as the difference between refractory periods at the two atrial sites. WPW patients showed significantly lower mean values of effective and functional refractoriness at both atrial sites and significantly higher mean values of D-ERP and D-FRP. Moreover, in calculating the highest normal values of D-ERP and D-FRP (as mean values of N plus 2SD) it was observed that WPW with abnormal values of D showed a statistically (chi 2 test) higher incidence (100%) of induced atrial fibrillation (AF). These findings indicate the existence of both an abnormal atrial electrophysiologic substrate and of a higher vulnerability in WPW. Finally, AF was induced generally at the site with the lower refractoriness (i.e. low lateral site). This should be taken into account when considering how atrial fibrillation can be induced more easily.

In cluster headache an adrenergic dysfunction of the pupillary sympathetic system can be demonstrated even during pain-free periods by instillation of tyramine in the conjunctival sac. In this study 10 patients with typical cluster headache syndrome exhibited a positive tyramine conjunctival test (minor mydriatic response in the pain side). As the adrenergic dysfunction may also involve the heart, possible neurogenic changes in ventricular repolarization were investigated in a group of patients with cluster headache by means of a hyperventilation test. When compared to controls, an increase of the QTc interval, a faster heart rate and a minor shortening of the QT interval, were observed. In all cases except one the T waves became bifid or inverted, sometimes showing a pseudoischemic aspect. Since the positive response to hyperventilation seems to depend on an asynchronous repolarization which can, in turn, be related to asymmetric sympathetic function, the present results seem to suggest the presence of a possible lateralization of the cardiac sympathetic function, in cluster headache patients.

The effects of isoproterenal (ISP) and methoxamine (MTX) infusion in 20 asymptomatic subjects with labile T wave were studied. In those treated with ISP the T wave showed an early negative trend and later became clearly positive in 5 subjects. In the majority of the subjects treated with MTX the T wave became positive. T wave changes match variations of both the ventricular gradient and, to a lesser degree, the QRS area. These changes were not related to heart rate or, in the subjects treated with MTX, to the baroreceptorial sensitivity deduced from the slope of the regression equation between R-R internal and systolic arterial pressure. The results of this study confirm the existence of a neurogenic mechanism affecting the electrocardiographic changes in T wave.

The dynamics of placental transfer of digoxin (beta-methyl-digoxin) has been studied in 20 pregnant women. The drug was administered in a single dose, intravenously, during labor. The samples drawn within the first hour after administration showed significantly lower fetal serum digoxin concentrations (SDC) than in the mother. No significant difference appeared in specimens collected after the first hour.

The authors have studied the correlation between digoxin clearance and glomerular filtration rate. This correlation was better than between digoxin clearance and creatinine clearance without reducing the error of a programed therapy.