Left ventricular noncompaction (LVNC) is a myocardial disorder probably due to the arrest of normal embryogenesis of the left ventricle. It could be isolated or associated with other extracardiac and cardiac abnormalities, including coronary artery anomalies. Despite the continuous improvement of imaging resolution quality, this cardiomyopathy still remains frequently misdiagnosed, especially if associated with other heart diseases. We report a case of LVNC association with both malposition of the great arteries and a very original coronary artery pattern.

Aims: Brugada syndrome (BrS) is an inherited channelopathy that can be characterized by mild right ventricular (RV) abnormalities that are not detectable with conventional echocardiography. The aim of this study was to evaluate the presence of RV abnormalities in BrS patients when compared with controls and a group of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using two-dimensional (2D) strain analysis. Methods and results: We enrolled 25 BrS, 15 ARVD/C patients, and 25 controls. Right and left ventricular dimension and systo-diastolic function were evaluated by conventional echocardiography. Longitudinal systolic strain (sS) peak, systolic and early diastolic strain rate of lateral RV segments were evaluated by 2D speckle tracking analysis. Left ventricle global and segmental strain measures were also evaluated. A reduced basal or mid-RV lateral sS were the parameters mostly associated with both BrS and ARVD/C. In BrS patients the minimum sS observed in these segments was significantly lower than that of controls (-28.9±3.2% vs. -32.3±3.2%, P: 0.002) but significantly greater than that evaluated in ARVD/C patients (-24.6 ±6.7%, P < 0.001 both vs. BrS and controls). No differences were found between the BrS and the control group when left ventricular strain measures were analysed. Conclusion: By 2D strain technique it is possible to observe mild abnormalities in RV systolic and diastolic function of BrS patients that are less pronounced than those observed in ARVD/C patients. These results help to better define the phenotypic characteristics of BrS patients and represent the basis for future studies aimed at testing their clinical usefulness in BrS patients.

Endocarditis of a prosthetic heart valve is a life-threatening condition that is associated with high morbidity and mortality. Perivalvular extension in infective endocarditis includes complications such as periannular or intramyocardial abscesses, pseudoaneurysms and fistulae. The incidence of perivalvular extension ranges from 10 to 30% in native valve endocarditis and 30 to 55% in prosthetic aortic-valve endocarditis. Herein, we describe a case of a 66-year-old man who presented endocarditis of a prosthetic aortic valve complicated by infective pseudoaneurysm with localization next to the right coronary sinus of Valsalva. Moreover, we underscore the importance of the diagnostic imaging tools options and surgical timing.

Background and aims: Anemia seems to be rather common in cardiac rehabilitation patients but it is not known whether it could influence cardiovascular performance indexes and prognosis immediately after an acute cardiac event. The purposes of this study were to define its prevalence and to investigate the safety and efficacy of an intensive exercise-based cardiac rehabilitation in patients with and without anemia. Methods: 436 participants (77% males; mean age 64 ± 13 years) were submitted to a two-week cardiac rehabilitation program consisting of low to medium intensity, individualized training with respiratory, aerobic and callisthenic exercises (three sessions daily, six times per week). A six-minute walking test was performed at enrolment and repeated at discharge together with a cardiopulmonary test. Results: Anemia, as defined according to World Health Organization criteria, was detected in 328 patients (75.2% of the entire population). The distance walked increased from 381 ± 117 m at baseline to 457 ± 110 m (p < 0.001) after a mean period of 12.4 ± 4 days. A direct correlation was found between hemoglobin concentrations and both the absolute distance walked (r = 0.48; p < 0.001) and peak VO2 (r = 0.39; p < 0.001). Anemic patients walked a significantly shorter distance at baseline and at discharge (p < 0.001); however, both groups showed the same increment in the distance walked: 76.0 ± 61 m vs 76.0 ± 60 m (p = 0.99). Conclusions: Our data indicate: 1) a high prevalence of anemia in the study population and 2) that, in spite of a clear reduction in exercise capacity, a moderate anemia does not preclude increments in cardiac performance during a short period of intensive, exercise-based cardiac rehabilitation.

Background. Although individual patient outcomes are highly variable, coronary artery anomalies may be associated with sudden cardiac death or acute coronary syndrome. Methods. We report 5 cases of anomalous origin of coronary arteries: a single coronary artery originating from the right sinus of Valsalva, a case of isolated anomalous right coronary artery originating separately from the left sinus of Valsalva, a case of right coronary artery originating between the right and left sinus of Valsalva, a case of anomalous left circumflex artery originating from the right sinus of Valsalva, and a case of anomalous left anterior descending coronary artery originating from the right sinus of Valsalva. Results. Although in one case the right coronary artery runned between the aorta and the right pulmonary artery, no significant alterations due to coronary artery compression or atheromatous lesions at the anomalous coronary ostia were observed. In all reported cases, symptoms were different as a result of cardiovascular comorbidities. All coronary anomalies were identified at coronary angiography, which was performed for other indications. Conclusions. The identification of a clear correlation between symptoms and coronary artery anomalies seems challenging in clinical practice. However, it is crucial to confirm or rule out the presence of coronary compression caused by the anomalous origin of coronary arteries.

Pseudocoarctation is a rare congenital anomaly characterized by aorta elongation and kinking, without significant obstruction. We report the case of an elderly patient with history of congestive heart failure (CHF) and aortic regurgitation (AR) who was referred for progressive exertional dyspnoea. After multimodal imaging evaluation, aortic coarctation with significant trans-stenosis gradient but mild luminal narrowing was diagnosed; this borderline patient was not addressed to repair, according to ESC guidelines and in spite of AHA ones. He rather met the criteria for pseudocoarctation diagnosis. An integration of functional and anatomical data is essential for a reliable diagnostic process in similar cases.

Background: Transthoracic enhanced echo Doppler of coronaries (CED) has the potential to detect coronary flow and its acceleration at the stenosis site over the entire left anterior descending coronary artery (LAD). CED has recently enhanced its feasibility thanks both to new technologies (convergent color Doppler mode) and new tomographic planes. As blood flow velocity (BFV) is inversely related to vessel radius elevated to the power, we hypothesized that even mild coronary narrowing plaque, as assessed by intravascular ultrasound (IVUS), can cause enough acceleration to be detected by CED. Methods: Fifty consecutive patients (pts) (age 55±12years, males 74%, BMI =28±4) scheduled for cath and IVUS were evaluated by CED in convergent color Doppler mode . Color guided pulsed waved Doppler mapping of the whole LAD (specifically the proximal, mid and distal part) was performed in order to attain for each segment maximal and reference BFV. Results: CED feasibility was 100%. IVUS showed 45 patients with mild severity atherosclerosis involving one or more segments of LAD and 5 with totally normal LAD. Maximal velocity was higher in the diseased segment than in the normal segments (54±25 cm/s vs 31±6 cm/s; p&lt;0.001); as the reference velocity was similar (30±6cm/s vs 29±6cm/s; p=ns), the percentage increase in velocity was also higher (77±56% vs 4±9%; p&lt;0.001). Using a cutoff value of a 22% increase in velocity, sensitivity and specificity to detect at least one plaque involving LAD was respectively 82% (37/45 pts) and 100% (5/5 pts) The location of the BFV acceleration (aliasing zone at color Doppler) strictly corresponded to IVUS plaque location in proximal and mid LAD: 34 pts showed concordant location (11 with proximal plaque, 10 with mid plaques and 15 with both segments plaques) and 11 discordant (8 pts with plaques missed and 3 with plaques misplaced by CED) (Cramer’s V = 0,84, P&lt;0,001). In corresponding segments lumen area stenosis (%) as assessed by CED (continuity equation) concurred with that assessed by IVUS (44±14 % vs. 37±16%) with r = 0,42 (p=0.014). Conclusion: BFV evaluation in the LAD by means of CED is feasible and reliable in assessing LAD mild atherosclerosis in a totally non-invasive way.

Background: Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient's therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated.Methods/design: The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension - both in the office and in ambulatory conditions over 24 h - and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n=84) or HBPT (n=168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets (<135/85 mmHg) 24 weeks and 48 weeks after randomization. In addition, the study will assess the psychological determinants of adherence and persistence to drug therapy, through specific psychological tests administered during the course of the study. Other secondary study endpoints will be related to the impact of HBPT on additional clinical and economic outcomes (number of additional medical visits, direct costs of patient management, number of antihypertensive drugs prescribed, level of cardiovascular risk, degree of target organ damage and rate of cardiovascular events, regression of the metabolic syndrome).Discussion: The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients.

Takotsubo cardiomyopathy (TTC) is a form of acute left ventricular dysfunction usually reversible and with favorable prognosis. Ventricular septal perforation (VSP) is a very rare life-threatening complication. Percutaneous closure of VSP, despite being challenging, is a possible alternative to surgical repair. We present the first case of an 84-year-old patient with a TTC-related VSP treated by percutaneous approach. The case highlights the need of reconsidering the worldwide accepted consideration of TTC as benignant and allows some speculations on the optimal management of VSP in terms of timing, patient selection and possible alternative interventions.

Introduction: Silent ischemia is an asymptomatic form of myocardial ischemia, not associated with angina or anginal equivalent symptoms, which can be demonstrated by changes in ECG, left ventricular function, myocardial perfusion, and metabolism. The aim of this study was to evaluate the prevalence of silent myocardial ischemia in a group of patients with asymptomatic carotid stenosis. Methods: A total of 37 patients with asymptomatic carotid plaques, without chest pain or dyspnea, was investigated. These patients were studied for age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of cardiac disease, and underwent technetium-99 m sestamibi myocardial stress-rest scintigraphy and echo-color Doppler examination of carotid arteries. Results: A statistically significant relationship (P = 0.023) was shown between positive responders and negative responders to scintigraphy test when both were tested for degree of stenosis. This relationship is surprising in view of the small number of patients in our sample. Individuals who had a positive scintigraphy test had a mean stenosis degree of 35% ± 7% compared with a mean of 44% ± 13% for those with a negative test. Specificity of our detection was 81%, with positive and negative predictive values of 60% and 63%, respectively. Conclusion: The present study confirms that carotid atherosclerosis is associated with coronary atherosclerosis and highlights the importance of screening for ischemic heart disease in patients with asymptomatic carotid plaques, considering eventually plaque morphology (symmetry, composition, eccentricity or concentricity of the plaque, etc) for patient stratification.

Aims: Carotid intima-media thickness (IMT) is one of the best non-invasive parameters for evaluating previous vascular lesions and could be used to identify a preclinical stage of the atherosclerotic process. The aim of our research was to develop an epidemiological study of the normal mean values of IMT of the common carotid artery, adjusted for age and sex, in the Italian population. Methods and results: In this multicenter study, a total of 1017 patients (596 males, mean age: 58.5\+13.2 years) were enrolled at four different Italian centers. Inclusion criteria were the absence of cardiovascular risk factors or presence of not more than one. Patients underwent two-dimensional echo-color Doppler scanning of the carotid arteries, adopting a high-definition vascular echographic apparatus and a 11-3 MHz linear electronic probe. The arithmetical mean of the IMT value was calculated. Data obtained from this study show the carotid IMT changes in relation to age and sex. In particular, it grows higher with increasing age, and is always higher in men than in women. Conclusion: In relation to the percentile distribution of the values in the population analyzed, the normal range of m- IMT could be established just on the basis of the patient's age and sex. In this way, the ultrasound scan operator can rely on a simple reference scheme. This will help to refine the use of carotid ultrasound as an excellent tool for detecting asymptomatic carotid alterations and patients at high risk for cerebral and cardiovascular disease.

Mutations in the lamin A/C gene (LMNA) were associated with dilated cardiomyopathy (DCM) and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup) in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic cardiac laminopathy.

Objective: There is a close link between heart failure and endothelial dysfunction. Brachial flow-mediated dilation (FMD) is a validated non-invasive measure of endothelial function. The aim of this study was to investigate the clinical correlates of FMD in patients with chronic heart failure (CHF). Design, setting, patients: Weevaluated 60CHFoutpatients (age 62 ± 14 years; 49 males, NYHA class 2.2 ± 0.7, left ventricular ejection fraction, LVEF, 33 ± 8%) taking conventional medical therapy (ACE-inhibitors and/or ARBs 93%, beta-blockers 95%) and in stable clinical conditions. Main outcome measures: The maximum recovery value of FMD was calculated as the ratio of the change in diameter (maximum-baseline) over the baseline value. Results: As compared with patients with a higher FMD, those with FMD below the median value (4.3%) were more frequently affected by ischemic cardiopathy (50 vs. 23%; p = 0.032) and diabetes mellitus (20 vs. 3%; p = 0.044), had a higher NYHA class (2.5 ± 0.5 vs. 1.9 ± 0.7; p< 0.001) and NT-proBNP (2,690 ± 3,690 vs. 822 ± 1,060; p = 0.001), lower glomerular filtration rate estimated by Cockcroft-Gault (GFRCG: 63 ± 28 vs. 78 ± 25; p = 0.001) and LVEF (29 ± 8 vs. 37 ± 9; p = 0.001), as well as more frequently showing a restrictive pattern (40 vs. 7%; p = 0.002). In a multivariate regression model (R2 = 0.48; p<0.001), FMD remained associated only with the NYHA class (p = 0.039) and diabetes mellitus (p = 0.024). Conclusions: This study demonstrates that a better functional status and absence of diabetes mellitus are associated to higher FMD regardless of the etiology of the cardiac disease.

OBJECTIVES: The purpose of this study is to assess the effectiveness of defibrillation testing (DT) in patients undergoing implantable cardioverter-defibrillator (ICD) insertion. BACKGROUND: Although DT is considered a standard procedure during ICD implantation, its usefulness has not been definitively proven. METHODS: The SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation) study is a prospective observational study designed to evaluate the outcome of 2 strategies: performing defibrillation testing (DT+) versus not performing defibrillation testing (DT-) during de novo ICD implants. No deviation from the centers' current practice was introduced. In all, 2,120 consecutive patients (836 DT+ and 1,284 DT-) age ≥18 years were enrolled at 41 Italian centers from April 2008 to May 2009 and followed up for 24 months until June 2011. The primary endpoint was a composite of severe complications at ICD implant and sudden cardiac death or resuscitation at 2 years. RESULTS: The primary endpoint occurred in 34 patients: 12 intraoperative complications (8 in DT+ group; 4 in DT- group) and 22 during follow-up (10 in DT+ group; 12 in DT- group). Overall, the estimated yearly incidence (95% confidence interval) was DT+ 1.15% (0.73 to 1.83) and DT- 0.68% (0.42 to 1.12). The difference between the 2 groups was negligible: 0.47% per year (-0.15 to 1.10). Mortality from any cause was similar at 2 years (adjusted hazard ratio: 0.97 [0.76 to 1.23], p = 0.80). CONCLUSIONS: In this large cohort of new ICD implants, event rates were similar and extremely low in both groups. These data indicate a limited clinical relevance for DT testing, thus supporting a strategy of omitting DT during an ICD implant. (Safety of Two Strategies of ICD Management at Implantation [SAFE-ICD]; NCT00661037).

Background: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. Methods and Results: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). Conclusion: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians.

Objectives; Nitrate-stimulated head-up tilt testing (HUT) is currently recommended to confirm the diagnosis of vasovagal syncope in subjects with syncope of unknown origin. Given the few data currently available, the aim of this study was to assess correlations between nitrateinduced HUT outcomes and the clinical characteristics of patients. Methods; Two hundred and thirty consecutive, otherwise healthy subjects with a history of recurrent unexplained syncope underwent HUT. After 10 min supine rest, they were tilted to 70°, and the test was potentiated by the administration of 300 μg of nitroglycerin after 20 min. Results Out of 178 subjects who underwent nitroglycerin administration during HUT, 95 fainted. At univariate Cox regression analysis, a reduced probability of VVS occurrence after nitrates was associated with greater systolic blood pressure and body mass index values, to male gender and smoking. At multivariate Cox regression analysis, only male gender (HR - 0.61; P - 0.039) and smoking (HR - 0.18; P - 0.001) remained significantly associated with HUT outcomes during the pharmacological phase of the test. Interpretation; Smokers and males are less likely to faint after nitrate administration during HUT than non-smokers and females. Further studies should clarify the possibility of improving the diagnostic power of HUT in these patients.

AimsClosed-loop stimulation (CLS) pacing has shown greater efficacy in preventing the recurrence of vasovagal syncope (VVS) in patients with a cardioinhibitory response to head-up tilt test (HUTT) compared with conventional pacing. Moreover, there is no conclusive evidence to support the superiority of CLS over the conventional algorithms for syncope prevention. This study retrospectively evaluated the effectiveness of CLS pacing compared with dual-chamber pacing with conventional specialized sensing and pacing algorithms for syncope prevention in the prevention of syncope recurrence in patients with refractory VVS and a cardioinhibitory response to HUTT during a long-term follow-up.Methods and resultsForty-one patients (44 male, 53 ± 16 years) with recurrent, refractory VVS (26 with trauma) and a cardioinhibitory response to HUTT who had undergone pacemaker implantation were included in the analysis. Twenty-five patients received a dual-chamber CLS pacemaker (CLS group) and 16 patients received a dual-chamber pacemaker with conventional algorithms for syncope prevention (conventional pacing group): 9 patients with Medtronic rate drop response algorithm and 7 patients with Guidant-Boston Scientific sudden brady response algorithm. During the follow-up (mean 4.4 ± 3.0 years, interquartile range 2.27.4 years) one patient (4) in the CLS group and six (38) in the conventional pacing group had syncope recurrences (P 0.016). The KaplanMeier actuarial estimate of first recurrence of syncope after 8 years was 4 in the CLS group and 40 in the conventional pacing group (P 0.010).ConclusionsThe results of this retrospective analysis show that, in order to prevent a recurrence of VVS in patients with a cardioinhibitory response to HUTT, dual-chamber CLS pacing was more effective than dual-chamber pacing with conventional algorithms for syncope prevention in preventing bradycardia-related syncope. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012.2012 © Published on behalf of the European Society of Cardiology.

Our aim was to perform a preliminary study of blood flow in the peripheral microcirculation in patients with heart failure. Cardiac patients were investigated to establish possiblemicrocirculatory changes due to this pathology. Weevaluated 16 patients (non-smokers, dislipidemic with hypercholesterolemia), receiving oral treatment and inNYHAclass 2.3 ± 0.5.Adilated cardiomyopathy (DCM) group was evaluated before cardiac resynchronization therapy (CRT) obtained by biventricular intra-cardiac defibrillator (ICD) implantation, and again 3 months after its implantation. We measured the ejection fraction (EF), peripheral blood flow (using laser Doppler) at the left wrist on the volar side, capillary morphology (using computerized videocapillaroscopy) on the nail bed of the 4th finger of the left hand, rheological status (using the LORCA), aswell as hematocrit, hemoglobin concentration, red blood cell (RBC) surface acetylcholinesterase (AchE), and homocysteine. Our data show that in the DCM vs. control group, peripheral flow did not depend only on the heart: throughout the study, blood flow did not change significantly compared to controls and was increased after CRT. There was no decrease in aggregation time. The blood flow did not alter RBC deformability or RBC surface AchE. Due to the lower oxygenation and to a non-significant increase in the number of capillaries after CRT, DCM patients are at higher cardiovascular risk than healthy subjects.

We report the case of a man affected by polymicrobial endocarditis developed on a St. Jude Medical Riata lead with a malfunction because of the outsourcing of conductors. The patient was treated with antibiotic targeted therapy and showed different bacteria at the blood cultures and then underwent transvenous leads extraction. Vegetations were highlighted on the caval, atrial, and ventricular tracts of the Riata lead, but the cultures were all negative. The externalization of Riata lead may cause the malfunction but it could also promote bacterial colonies and vegetations. In conclusion, looking for early signs of infection is mandatory during Riata leads follow-up checks.

Aims: Implantable cardioverter defibrillators (ICD) can prevent sudden cardiac death by delivering high-energy shocks in patients at risk of life-threatening ventricular tachyarrhythmias. Patients may be anxious about receiving inappropriate shocks in case of device or lead system malfunction, or about failing to receive needed therapy for the same reason. New devices include programmable vibrating patient notifiers (PN), which, by warning patients of a possible device dysfunction, might lower device-related anxiety. PAtient NOtifier feature for Reduction of Anxiety: A multicentre ICD study (PANORAMIC) is a multicentre, randomized, clinical trial designed to examine the effects of the awareness of an active vibrating alert system on device-related anxiety. Methods: The trial will randomly assign 356 patients in a 1:1 design to a control group (PN OFF) vs. a treatment group (PN ON). Patients will be followed for 12 months, with visits scheduled at 6 and 12 months. During clinical follow-up visits, the ICD will be interrogated, and all patients will complete the Hospital Anxiety and Depression Scale and a device-related anxiety questionnaire. The sensitivity and specificity of PN, the effect of personality on anxiety, using the Type D scale (DS14), the number of delivered appropriate and inappropriate ICD therapies, changes in anxiety related to the delivery of appropriate or inappropriate shocks, crossovers from the assigned group, the number of hospitalizations, and the mortality rate will also be assessed.

The aim of this study was to evaluate the clinical efficacy and safety of remote monitoring in patients with heart failure implanted with a biventricular defibrillator (CRT-D) with advanced diagnostics. Methods and results: The MORE-CARE trial is an international, prospective, multicentre, randomized controlled trial. Within 8 weeks of de novo implant of a CRT-D, patients were randomized to undergo remote checks alternating with in-office follow-ups (Remote arm) or in-office follow-ups alone (Standard arm). The primary endpoint was a composite of death and cardiovascular (CV) and device-related hospitalization. Use of healthcare resources was also evaluated. A total of 865 eligible patients (mean age 66 ± 10 years) were included in the final analysis (437 in the Remote arm and 428 in the Standard arm) and followed for a median of 24 (interquartile range = 15–26) months. No significant difference was found in the primary endpoint between the Remote and Standard arms [hazard ratio 1.02, 95% confidence interval (CI) 0.80–1.30, P = 0.89] or in the individual components of the primary endpoint (P > 0.05). For the composite endpoint of healthcare resource utilization (i.e. 2-year rates of CV hospitalizations, CV emergency department admissions, and CV in-office follow-ups), a significant 38% reduction was found in the Remote vs. Standard arm (incidence rate ratio 0.62, 95% CI 0.58–0.66, P < 0.001) mainly driven by a reduction of in-office visits. Conclusions: In heart failure patients implanted with a CRT-D, remote monitoring did not reduce mortality or risk of CV or device-related hospitalization. Use of healthcare resources was significantly reduced as a result of a marked reduction of in-office visits without compromising patient safety. Trial registration: NCT00885677. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

A novel mutation in the Lamin A/C gene (LMNA c.418_438dup) was detected in the index patient and in additional family members with diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) and history of sudden cardiac death. The functional characterization of this LMNA mutant was performed in cultured HL-1 cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs and subjected to confocal microscopy analysis and hypoxic stress conditions in 100% N2 for 8h. Mutated LMNA was clearly expressed in aggregates of different sizes and not uniformly distributed along the nuclear envelope as WT LMNA. Moreover, the mutated LMNA variant causes perturbation in nuclear shape and Nuclear Pore Complexes organization. Of note, we observed that under hypoxic conditions nuclear envelopes expressing mutated LMNA become leaky, leading a nuclear fluorescent marker to escape into the cytoplasm. This indicates that, under cell stressing conditions, the nucleo-cytoplasmic compartmentalization is affected in cardiomyocytes expressing this LMNA mutation, inducing, as final fatal consequence, cell apoptosis. In conclusion, we not only open new avenues to gain more insights in the pathogenesis of ARVC and to conceive novel therapeutic strategies but we also shed lights on the role of nuclear Lamin A in the physio-pathology of cardiomyocytes.

Background Post-treadmill digital echocardiography (post-TME) is the most widely used form of exercise echocardiography, but ischemia can rapidly resolve in the postexercise period; peak upright bicycle digital echocardiography (UBE) has the advantage of providing images at peak exercise that reflect normal physiology. However, the comparative accuracy of the two methods in detecting ischemia in the same patients is unknown. To compare the relative diagnostic value of peak UBE and post-TME in detecting coronary artery disease, both tests were performed in 86 consecutive patients undergoing coronary angiography. Methods Eighty-six patients referred for evaluation of coronary disease underwent peak UBE (starting at 25 W, with 25-W increments every 3 min) and post-TME (Bruce protocol) in a random sequence. Digitized images of peak UBE and post-TME were interpreted in a random and blinded fashion. Results More transient wall motion abnormalities were detected with peak UBE than post-TME (55 vs 42, P <.001), and such exercise-induced wall motion abnormalities were more extensive (5.5 ± 3.0 vs 3.4 ± 2.1 dyskinetic segments, P <.001) and more severe (regional wall motion score index, 2.7 ± 0.5 vs 2.5 ± 0.5; P =.003). By angiography, 59 patients had coronary artery disease (a coronary stenosis of ≥50% diameter narrowing); the sensitivity of peak UBE for detecting coronary artery disease was greater than that of post-TME in the population as a whole (88% vs 66%, P <.01) and in the single-vessel subgroup (72% vs 44%, P <.05), with no worsening in specificity (89% vs 89%, P = NS). Conclusions Peak UBE is more capable of detecting ischemia than post-TME, and this is achieved with no worsening of specificity. Thus, peak UBE should be preferred in patients able to perform bicycle exercise.

Background: A systematic evaluation focused on sensitivity and specificity of head-up tilt testing (HUT) for diagnosing vasovagal syncope has not been previously performed. We conducted a meta-analysis of studies comparing HUT outcome between patients with syncope of unknown origin and control subjects without previous syncope. Methods: We searched Pubmed and Embase databases for all English-only articles concerning case-control studies estimating the diagnostic yield of HUT, and selected 55 articles, published before March 2012, including 4361 patients and 1791 controls. The influence of age, test duration, tilt angle, and nitroglycerine or isoproterenol stimulation on tilt testing outcome was analyzed. Results: Head-up tilt testing demonstrated to have a good overall ability to discriminate between symptomatic patients and asymptomatic controls with an area under the summary receiver-operating characteristics curve of 0.84 and an adjusted diagnostic odds ratio of 12.15 (p < 0.001). A significant inverse relationship between sensitivity and specificity of tilt testing for each study was observed (p < 0.001). At multivariate analysis, advancing age and a 60° tilt angle showed a significant effect in reducing sensitivity and increasing specificity of the test. Nitroglycerine significantly raised tilt testing sensitivity by maintaining a similar specificity in comparison to isoproterenol. Conclusions: The results from this meta-analysis show the high overall performance of HUT for diagnosing vasovagal syncope. Our findings provide useful information for evaluating clinical and instrumental parameters together with pharmacological stressors influencing HUT accuracy. This could allow the drawing of tilt testing protocols tailored on the diagnostic needs of each patient with unexplained syncope.

Purpose. Aim of our study was to evaluate in a group of patients with dilated cardiomyopathy (DC) the evolution of systolic and diastolic ventricular function (specifically LV ejection fraction [EF] and the S/D pulmonary waves) after 15 years of follow-up. Methods. In this prospective study, in 122 patients with DC, EF and S/D were evaluated for the first time in 1995 and the second time 15 years after in the survivors. After 15 years, the vital status was ascertained by contacting patients or their relatives by phone. Results. At baseline we enrolled 92 males and 30 females with DC, with mean age 58±11 years,. LVEF=28.6±6.5% and LV end diastolic diameter= 65.41±7.1 mm. After 15 years, only 37 survived; of whom 18 accepted to undergo a second echocardiographic study. In the survivors revaluated LVEF, and S/D ratio did not show significant variation with respect to the baseline study (Figure 1 and 2). In Figure 1 you can appreciate that LVEF remained stable or mildly improved. In 2 cases it worsened but in 2 cases, it normalized, probably because of a reversible myocardial injury (probably a myocarditis improperly defined as cardiomyopathy at the time of accrual). In figure 2 you can see that S/D ratio tends to worsen toward a restrictive physiology. Conclusion. In these preliminary data, patients with dilated cardiomyopathy with every etiology had a poor long term prognosis, irrespective to the medical treatment. Patients who survived after 15-years, showed, on average, a rather stable systolic and diastolic function. Of interest, in few cases LV function may striking improve, probably because of reversible pathological process unidentified at the first evaluation.

Background: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodinecontaining antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. Aim of the Study: To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. Results: Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17% and, as expected, it was significantly higher in females than males (33% vs 13%; p<0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. Conclusions: Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

Aims To evaluate the independent prognostic role of two-dimensional (2D) strain measures reflecting global longitudinal left ventricular (LV) systolic function in outpatients affected by chronic heart failure (CHF). Methods and results Global longitudinal LV systolic strain (GLS) was assessed in 308 outpatients affected by CHF, by analyzing standard views with 2D speckle tracking technique. During a mean follow-up of 26 ± 13 months 37 patients died (29 due to cardiovascular causes), 10 patients underwent heart transplantation, and 75 patients experienced at least 1 episode of hospitalization due to acute decompensated heart failure (ADHF). Thirty-one patients without a history of major ventricular arrhythmic events experienced the occurrence of ventricular fibrillation and/or tachycardia or sudden death was observed. Multivariate Cox regression analysis showed that GLS was significantly associated with all-cause mortality (HR: 1.15; 95%CI: 1.02-1.30; P: 0.026), cardiovascular death (HR: 1.20; 95%CI: 1.04-1.39; P: 0.011), cardiovascular death or heart transplantation (HR: 1.24; 95%CI: 1.09-1.41; P: 0.001), ADHF-related hospitalizations (HR: 1.15; 95%CI: 1.05-1.25; P: 0.003), and arrhythmic events (HR: 1.17; 95%CI: 1.03-1.33; P: 0.018). Conclusions Quantifying LV longitudinal systolic function in CHF outpatients on the basis of 2D speckle tracking analysis provides a new parameter that independently predicts patient outcome, thus, strengthening its possible role in current clinical practice.

Aims The involvement of arterial baroreflex function in the pathophysiology of vasovagal syncope (VVS) is controversial, and there are no published data supporting its clinical usefulness. The aim of this study was to evaluate the role of arterial baroreflex sensitivity (BRS) at baseline and during head-up tilt testing (HUT) in predicting the recurrence of VVS. Methods and results The study involved otherwise healthy patients with a history of unexplained syncope who underwent diagnostic HUT by being tilted to 70° after 10 min supine rest; the test was potentiated by the administration of 300 g of nitroglycerine (NTG) after 20 min. Beat-to-beat heart rate and systolic blood pressure were continuously recorded, and the sequence method was used to measure arterial baroreflex control of heart rate. The 190 enrolled patients were followed up for 18 ± 6 months, during which 34 experienced a total of 90 episodes of syncope recurrence. In a stepwise multivariate analysis, female gender [hazard ratio (HR): 2.74; P = 0.008], the presence of ≥3 syncope events before HUT (HR: 3.36; P = 0.004), and BRS below median value after the start of HUT or after the administration of NTG (HR: 3.79; P = 0.006) were significantly and independently associated with the recurrence of syncope. Moreover, when a BRS value of less than the median was added to the other independent factors in a stepwise model, a significant increase in discrimination (C-index: 0.77) and model fitting (P = 0.001) was observed. Conclusion Reduced BRS during HUT has independent and incremental value in predicting the recurrence of syncope, thus supporting its potential usefulness in the clinical management of patients.

In heart failure (HF) patients, an impairment of the renal function, as well as a worsening of this condition, is frequently observed and both have been demonstrated to be independently associated with a greater morbidity and mortality [1] and [2]. Over the last years, the role of an increased central venous pressure (CVP) during acute decompensated heart failure (ADHF) in determining worsening renal function (WRF) has been well defined [3], but only few data about its role in chronic patients are available [4]. We sought to better define the predictors of a worsening renal function in a group of outpatients affected by chronic HF (CHF) in stable clinical conditions, focusing on non-invasive parameters reflecting right ventricular pressure. We enrolled 245 outpatients with a diagnosis of CHF (ESC criteria), with a left ventricular ejection fraction (LVEF) ≤ 45%; in stable clinical conditions from at least 30 days; in conventional medical and electrical therapy; and who completed 12-month follow-up. The protocol was approved by the local ethics committee and all the enrolled patients gave their informed consent to take part. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5]. At baseline the presence of ischemic heart disease, arterial hypertension and diabetes mellitus was recorded. NYHA class and arterial pressure were evaluated.

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a common airways disease recognized as an independent cardiovascular risk factor. It is often associated with obesity, diabetes and dyslipidemia. Its pathophysiological consequences (hypoxia, hypercapnia, micro-arousals, sympathetic hyperactivity, oxidative stress, systemic inflammation and hyper-coagulability) are implicated in the development of hypertension, endothelial dysfunction and higher intima-media thickness (IMT) values, all elements known to lead to atherosclerosis. The study aim was to demonstrate a relationship between OSAS duration and IMT values and to confirm how OSAS severity could influence IMT (a marker of atherosclerosis). Methods: We enrolled 156 patients (125 men, mean age: 60 ± 12 years) affected by OSAS of different severity: 111 (71%) were in CPAP therapy; some of the population were also affected by hypertension [102 (65%)], dyslipidemia [52 (33%)] and diabetes [38 (24%)]. Patients underwent evaluation of carotid artery IMT and answered a questionnaire investigating the time of onset (confirmed by a person aware of the patient's previous sleeping habits) and the duration of the disease. Results: We found a statistically significant higher IMT value in patients with longer-lasting disease (OSAS duration in IMT < 0.9 mm: 120 (60-192) months versus OSAS duration in IMT ≥ 0.9 mm: 200 (120-310) months; p < 0.001). OSAS severity is positively related to IMT values. We found a positive relationship between IMT and OSAS duration [r = 0.34; p < 0.001] and between AHI and IMT [r = 0.51; p < 0.001]. Conclusions: Our study shows that the duration of OSAS and its severity are important factor related with higher values of IMT and hence with a higher risk of atherosclerosis.

Although the pathophysiology of vasovagal syncope is not completely understood, the involvement of sympathetic nervous system alterations has been suggested. Since predisposition to fainting during orthostatic challenge may be associated with genetic variations, we sought to explore the role of genetic polymorphisms affecting sympathetic nervous system function in the susceptibility to tilt-induced vasovagal syncope. We genotyped 129 subjects with recurrent unexplained syncope who underwent tilt testing, and investigated the recurrence of syncope. The analysed polymorphisms were Arg492Cys (ADRA1A gene), Ser49Gly and Arg389Gly (ADRB1), Arg16Gly and Gln27Glu (ADRB2), 825C/T (GNB3), -1021C/T (DBH) and S/L (SLC6A4). No association of the aforementioned genetic variants with both tilt test outcomes and new syncopal episodes during follow-up was found. None of the considered polymorphisms influencing sympathetic activity is a major risk factor for vasovagal syncope in Italian patients.

Introduction. Pulmonary venous flow transesophageal Doppler recording is a reliable marker of LV diastolic function. However, there are only few data in literature concerning its prognostic role. Furthermore, to date, no study with long-term follow up compared the relative prognostic value of Transmitral and Pulmonary venous flow Doppler recordings. Purpose. Aim of our study was to establish the prognostic impact of LV diastolic function as assessed by Transmitral flow and Pulmonary Venous Flow (PVF) transesophageal Doppler recording in patients with dilated cardiomyopathy (DC). Methods. One hundred and twenty two patients affected by DC with different etiologies were consecutively enrolled in 1995. They were all on optimized therapy. They underwent a TEE Doppler study. Thus PVF was evaluated with the most reliable approach. The following parameters were measured: peak systolic and diastolic PV wave ratio (S/D), E and A mitral wave ratio (E/A), mitral E deceleration time (EDT) and the time difference between PV atrial reversal (Ar) and mitral A wave duration (A). After 15 years the vital status was ascertained by contacting patients or their relatives by phone. Results. During the follow-up period (mean 13,5 +/- 0,8 years) 81 pts (66%) had events (71 died and 10 underwent heart transplantation); no pts were lost to follow-up. LVEF was 28.6±6.5%, LVEDD 65.41±7.1 mm. E/A ratio couldn’t be evaluated in 21 cases because of E and A wave fusion secondary to high heart rate. The multivariate analysis showed that a 2-strata composite variable (diastolic risk) attained by pulmonary waves and A mitral wave (worse category= S/D ratio &lt;1 or S/D&gt;=1 and Ar-A &gt;0) was the best single diastolic variable that predicts hard events in the long term follow-up (hazard ratio = 3,13 with CI = 1,8-5,3, p&lt;0.001, see graph). Other Doppler indexes of diastolic function were not significant at the multivariate analysis. This was due to better prediction of death of the worse category of diastolic risk with respect to the E/A ratio. Conclusion. Our data show that LV diastolic function has important prognostic role in dilated cardiomyopathy when it is best assessed by Pulmonary Venous flow (S/D) combined with A-Ar.

Background: Cardiac resynchronization therapy (CRT) is effective in patients with heart failure, but 30% to 50% of subjects are classified as nonresponders. Identifying responders remains a challenging task. Aims: The LODO-CRT trial investigated the association between left ventricular contractile reserve (LVCR) and clinical and echocardiographic long-term CRT response. Methods: This is a multicenter, prospective, observational study. Left ventricular contractile reserve was detected using a dobutamine stress echocardiography test, defined as an ejection fraction increase of >5 points. Clinical CRT response was defined as the absence of major cardiovascular events (ie, cardiovascular death or heart failure hospitalization). Echocardiographic response was defined as a left ventricle end-systolic volume reduction of >10%. Results: A total of 221 CRT-indicated patients were studied (80% presented LVCR). During a mean follow-up of 15 ± 5 months, 17 patients died and 16 were hospitalized due to heart failure. The proportion of clinical responders was 155 (88%) of 177 and 33 (75%) of 44 (P =.036) in the groups with and without LVCR, respectively. Kaplan-Meier analysis showed a significant difference in cardiac survival/hospitalization between patients with and without LVCR. The proportion of echocardiographic responders was 144 (87%) of 166 and 16 (42%) of 38 in the groups with and without LVCR (P <.001), respectively; LVCR showed 90% sensitivity and 87% positive predictive value to prefigure echocardiographic CRT responders. Multivariable analysis identified LVCR and interventricular dyssynchrony as independent predictors of CRT response. The concomitant presence of both factors showed 99% specificity and 83% sensitivity in detecting responders. Conclusion: The presence of LVCR helps in predicting a clinical and echocardiographic CRT response. Concomitant assessment of LVCR and interventricular dyssynchrony accurately stratifies responder and nonresponder patients.

Cardiac Implantable Electronic Device (CIED) infections are an emerging clinical issue. There are no national recommendations on the management of these infections, also due to the limited number of dedicated and high quality clinical studies. Therefore, researchers from southern Italian centres have decided to share the clinical experience gathered so far in this field and report practical recommendations for the diagnosis and treatment of adult patients with CIED infection or endocarditis. Here we review the risk factors, diagnostic issues (microbiological and echocardiographic) and aetiology, and describe extensively the best therapeutic approach. We also address the management of complications, follow-up after discharge and the prevention of CIED infections. In this regard, a multidisciplinary approach is fundamental to appropriately manage the initial diagnostic process and the comorbidities, to plan proper antimicrobial treatment and complete percutaneous hardware removal, with the key support of microbiology and echocardiography.

Background: To compare head-up tilt testing (HUT) outcomes and hemodynamic responses, and the prevalence and correlates of prodromes, in elderly and younger patients with suspected vasovagal syncope (VVS). Methods: Consecutive outpatients with a history of recurrent unexplained syncope underwent HUT by being tilted to 70°; the test was potentiated by the administration of 300 μg of nitroglycerine after 20 minutes. Occurrence of VVS and hemodynamic responses during passive and nitroglycerine phases of HUT were evaluated; symptoms preceding HUT-induced syncope were recorded, together with heart rate and arterial blood pressure values. Results: Four hundred and sixty of the 743 patients were HUT positive: 156 fainted during the unmedicated phase and 304 after nitroglycerine administration. The patients aged ≥65 years (n = 102) experienced VVS more frequently during the pharmacological stage of HUT; the overall rate of positive results was similar to that observed in the patients aged 36-64 years (n = 329) and only slightly lower than that observed in those aged ≤35 years (n = 312). In the older patients, who experienced fewer and mainly prodrome-free spontaneous syncopal episodes, HUT increased the number of premonitory symptoms, and there were no significant age-related differences in symptom prevalence or timing or the patients' hemodynamic characteristics. Conclusions: The rate of VVS induced by nitroglycerine-potentiated HUT is similar in elderly and younger patients. In the former, nitroglycerine- potentiated HUT significantly increases the prevalence of prodromes in comparison with spontaneous episodes, which suggests that it may be useful not only for diagnosis but also for patient counseling.

Nine patients (pts) with angiographically normal coronary arteries were submitted to absolute coronary flow reserve (CFR) in the distal left circumflex (LCx) coronary artery (specifically in the marginal branch that was insonified by a modified four-chamber view) using a novel non-invasive method (base-adenosine transthoracic echo Doppler in convergent color Doppler mode ). CFR in the distal left anterior descending coronary artery was attained as well using the same Doppler modality. Results: In this non consecutive series of patients blood flow velocity in LCx was adequately recorded at baseline and during adenosine infusion. However blood flow velocity recording in the LCx was more difficult to attain during hyperemic phase than during the basal one; in fact it was attained only in the pre-tachicardic phase of the hyperemia in 4 pts (45%). CFR attained in the LCx strictly concorded with that attained in the left anterior descending coronary artery territory (R= 0.94, p&lt;0.001) (see graph) so relative CFR was close to 1 (0,96 +/-0.08). Conclusion: In this preliminary non-consecutive study CFR in LCx seems feasible enough to have clinical potential value. Its strict agreement with LAD CFR over a wide range of values in patients with angiographically normal coronary arteries and expected homogeneous microcirculatory function indicate its potential higly reliability in terms of pathophysiology assessment of coronary function.

Background: Adenosine intravenous infusion is used to evaluate Coronary Flow Reserve (CFR) in patients with coronary artery disease. However, the proposed duration of adenosine infusion ranges from 90 seconds to 5 minutes. Therefore the optimal duration of Adenosine infusion to obtain maximal vasodilator effect still remains uncertain. Aim: Purpose of this study was to define the optimal duration of adenosine intravenous (iv) infusion to elicit maximal coronary hyperemic effect. Materials and Methods: We consecutively enrolled 101 patients between June 2009 and May 2011. The mean age was 53±11 years (64% male, 36% female), and ejection fraction (EF) was 59±13%. All patients underwent blood flow velocity Doppler recording in the distal left anterior descending coronary artery (LAD) at baseline and during adenosine iv infusion via a pump at the dosage of 0.14 mg/Kg/min over 5 minutes. Coronary blood flow velocity in LAD was continuously recorded by a well-validated non invasive approach: enhanced transthoracic Color-guided Pulsed-Wave Doppler recording. The time to maximal hyperaemic effect was obtained by activating a built-in chronometer at the starting of adenosine infusion. Results: We found that the peak effect occurred at 72 ± 32 seconds (see histogram). The peak effect occurred within 90 sec in 80 pts (66%) and after 90 sec in 46 pts (34%). In no pt, peak hyperaemic effect took place beyond 3 minutes. In addition in the vast majority of cases (90%) the maximal vasodilatatory effect was reached before the tachycardic phase of adenosine effect. Conclusions: The results of this study seem to indicate that the optimal duration of adenosine infusion to evaluate CFR should be at least 3 minutes.

Background Several previous implantable loop recorder (ILR) studies have shown bradyarrhythmic events requiring a pacemaker implantation in a significant proportion of patients with unexplained syncope (US). The aim of this observational, two-centre, study was to identify the predictive factors for pacemaker implantation in a population of patients receiving an ILR for US with suspected arrhythmic aetiology. Methods Fifty-six patients (mean age 68 years, 61% male) with a history of US and negative cardiac and neurological workup, who underwent ILR implantation, were enrolled. After the implantation, a follow-up visit was undertaken after symptomatic events or every 3 months in asymptomatic subjects. The end-point of the study was the detection of a bradyarrhythmia (with or without a syncopal recurrence) requiring pacemaker implantation. Results After a median ILR observation of 22 months, a clinically significant bradyarrhythmia was detected in 11 patients (20%), of which 9 cases related to syncopal relapses. In the multivariable analysis, three independent predictive factors for pacemaker implantation were identified: an age > 75 years (odd ratio [OR]: 29.9; p = 0.035); a history of trauma secondary to syncope (OR: 26.8; p = 0.039); and the detection of periods of asymptomatic bradycardia, not sufficient to explain the mechanism of syncope, during conventional ECG monitoring (through 24 h Holter or in hospital telemetry), performed before ILR implantation (OR: 24.7; p = 0.045). Conclusions An advanced age, a history of trauma secondary to syncope, and the detection of periods of asymptomatic bradycardia during conventional ECG monitoring were independent predictive factors for bradyarrhythmias requiring pacemaker implantation in patients receiving an ILR for US.

BACKGROUND: The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue. METHODS AND RESULTS: We studied 106 consecutive patients (62 men and 44 women; age, 35.6±18 years) with arrhythmogenic right ventricular cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk factors such as syncope, nonsustained ventricular tachycardia, familial sudden death, and inducibility at programmed ventricular stimulation. During follow-up of 58±35 months, 25 patients (24%) had appropriate ICD interventions and 17 (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months, the actual survival rate was 100% compared with the VF/ventricular flutter-free survival rate of 77% (log-rank P=0.01). Syncope significantly predicted any appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83 to 4.67; P=0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95% confidence interval, 1.39 to 5.63; P=0.005). The positive predictive value of programmed ventricular stimulation was 35% for any appropriate ICD intervention and 20% for shocks for VF/ventricular flutter, with a negative predictive value of 70% and 74%. None of the 27 asymptomatic patients with isolated familial sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate ICD interventions, and 18 (17%) had device-related complications. CONCLUSIONS: One fourth of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had appropriate ICD interventions. Syncope was an important predictor of life-saving ICD intervention and is an indication for ICD. Prophylactic ICD may not be indicated in asymptomatic patients because of their low arrhythmic risk regardless of familial sudden death and programmed ventricular stimulation findings. Programmed ventricular stimulation had a low predictive accuracy for ICD therapy.

Pulmonary Venous Flow as Assessed by Transesophageal Echocardiography Independently Predicts Mortality in Patients With Dilated Cardiomyopathy. A Thirteen Year Follow-up Study Background: Pulmonary venous flow (PVF), optimally studied during transesophageal echocardiography is a better index of diastolic restricted physiology in dilated cardiomyopathy (DCM) but it’s not known if it has an incremental value over the more established prognosticators such as LV ejection fraction (LVEF) and peak VO2 in the long term. Methods: This study included 122 patients (pts) with DCM (92 males, 58+/-11 years, LVEF= 28%+/-6), stable and in sinus rhythm. All pts underwent transesophageal echocardiography with color guided pulsed wave Doppler recording of PVF and transmitral flow; peak systolic and diastolic PVF wave ratio (S/D), E and A mitral wave ratio (E/A), mitral E deceleration time and the time difference between PVF atrial reversal (Ar) and mitral A wave duration (A) were measured. Others parameters attained were: LVEF, inspiratory collapse of the inferior vena cava, mitral regurgitation peak VO2, creatininemia. Cardiac events were defined as death or heart transplantation. Results: During the follow-up period (mean 13. 5+/- 0. 8 years) 81 pts (66%) had events; no pts were lost to follow-up. A 4-strata composite variable (high risk) attained by both LVEF (worse category= LVEF&lt; 25%) and LV diastolic function (worse category= S/D ratio&lt;1 or S/D&gt;=1 and Ar-A &gt;0) was the best predictor of hard events (see table). Other Doppler indices of diastolic function were not significant at the multivariate analysis. Conclusion: In the long term PVF and LVEF are the best predictors of outcome in pts with DCM.

AimsThe long-term impact of implantable device-related complications on the patient outcome has not been thoroughly evaluated. The aims of this retrospective, bi-centre study were to analyse the rate and nature of device-related complications requiring surgical revision in a large series of patients undergoing device implantation, elective generator replacement and pacing system upgrade and to systematically assess the impact of such complications on patient outcome and healthcare utilization.Methods and resultsData from 2671 consecutive procedures (1511 device implantations, 1034 elective generator replacements, and 126 pacing system upgrades) performed between January 2006 and March 2011 were retrospectively analysed. The outcome measures recorded were complication-related mortality, number of re-operations, need for complex surgical procedures, number of re-hospitalizations, and additional hospital treatment days. Over a median follow-up of 27 months, the overall rate of complications was 2.8% per procedure-year [9.5% in cardiac resynchronisation therapy (CRT) device implantation, 6.1% in pacing system upgrade, 3.5% in implantable cardioverter defibrillator implantation, 1.7% in pacemaker implantation, and 1.7% in generator replacement). The procedure with the highest risk of complications was CRT device implantation (odds ratio: 6.6; P < 0.001); these complications primarily involved coronary sinus lead dislodgement and device infection. Patients with complications had a significantly higher number of device-related hospitalizations (2.3 ± 0.6 vs. 1.0 ± 0.1; P < 0.001) and hospital treatment days (15.7 ± 25.1 vs. 3.6 ± 1.1; P < 0.001) than those without complications. Device infection was the complication with the greatest negative impact on patient outcome.ConclusionCardiac resynchronisation therapy implantation was the procedure with the highest risk of complications requiring surgical revision. Complications were associated with substantial clinical consequences and a significant increase in the number and length of hospitalizations.

Objective: The study aim was to compare C3 levels with the common carotid artery intima-media thickness (CCAIMT) in subjects of both genders, with a wide range of BMI, independently of age, gender, and abdominal obesity. Method: 140 euthyroid, mainly overweight/obese subjects (age 18-30 years) were examined. BMI, waist circumference, blood pressure, fasting insulin, glucose, lipids, C3 and C-reactive protein serum concentrations, and insulin resistance degree (estimated by homeostasis model assessment for insulin resistance (HOMAIR)) were measured. Results: CCA-IMT was positively (p < 0.001) correlated with BMI, waist circumference, systolic and diastolic blood pressures, HOMAIR, and insulin, CRP, and C3 serum levels. The multiple linear regression analysis showed that only male gender and waist circumference maintained an independent relation with the CCA-IMT. Conclusion: This study suggests that central fat accumulation and male gender independently increase the thickness of the arterial wall, whereas inflammation and inflammatory markers do not have an independent effect on this parameter.

Background: Remote monitoring (RM) permits home interrogation of implantable cardioverter defibrillator (ICD) and provides an alternative option to frequent in-person visits. Objective: The Italia-RM survey aimed to investigate the current practice of ICD follow-up in Italy and to evaluate the adoption and routine use of RM. Methods: An ad hoc questionnaire on RM adoption and resource use during in-clinic and remote follow-up sessions was completed in 206 Italian implanting centers. Results: The frequency of routine in-clinic ICD visits was 2 per year in 158/206 (76.7%) centers, 3 per year in 37/206 (18.0%) centers, and 4 per year in 10/206 (4.9%) centers. Follow-up examinations were performed by a cardiologist in 203/206 (98.5%) centers, and by more than one health care worker in 184/206 (89.3%) centers. There were 137/206 (66.5%) responding centers that had already adopted an RM system, the proportion of ICD patients remotely monitored being 15% for single- and dual-chamber ICD and 20% for cardiac resynchronization therapy ICD. Remote ICD interrogations were scheduled every 3 months, and were performed by a cardiologist in 124/137 (90.5%) centers. After the adoption of RM, the mean time between in-clinic visits increased from 5 (SD 1) to 8 (SD 3) months (P<.001). Conclusions: In current clinical practice, in-clinic ICD follow-up visits consume a large amount of health care resources. The results of this survey show that RM has only partially been adopted in Italy and, although many centers have begun to implement RM in their clinical practice, the majority of their patients continue to be routinely followed-up by means of in-clinic visits.

Background: The obstructive sleep apnoea syndrome (OSAS) is a common airways disease which often involves cardiovascular structures, causing vessel inflammation as well as hypoxia, induced by difficulties in the passage of air through the upper airways. Aim of our research is to evaluate the effects of Continuous Positive Airway Pressure (CPAP) on the syndrome itself and the patients cardiovascular risk profile, practically adopting Flow-Mediated Vasodilation (FMD) technique to evaluate endothelial function. Methods and results: We enrolled 63 patients (49 males and 14 female, mean age: 54 ± 10 years) subdivided into four groups: high cardiovascular risk factors, no CPAP therapy, CPAP therapy started less- and more than 3 months before. The patients underwent FMD of the brachial artery using a high resolution ultrasonograph connected to an image analysis system. The maximum recovery value was calculated as the ratio (maximum-baseline) of the change in diameter over the baseline value. Data obtained from this study demonstrate the significant reversibility of FMD in patients treated for more than 3 months with CPAP therapy (Group 4). Conclusions: Our study shows the importance of administering CPAP therapy for more than 3 months in patients suffering from OSAS to improve EF to a level equal to high cardiovascular risk subjects probably due to a recovery from the systemic hypoxia. Besides, our work points out the importance of FMD as a clinical tool able to point out any improvement or regression after therapies.

Cardiac resynchronization therapy defibrillators (CRT-D) are able to monitor various parameters that may be combined by an automatic algorithm to provide a heart failure risk status (HFRS). We sought to validate the HFRS for stratifying patient risk, evaluate its association with heart failure (HF) symptoms, and investigate its utility for triage of automatic alerts.

Lamin A/C is a structural protein of the nuclear envelope (NE) and cardiac involvement in Lamin A/C mutations was one of the first phenotypes to be reported in humans, suggesting a crucial role of this protein in the cardiomyocytes function. Mutations in LMNA gene cause a class of pathologies generically named 'Lamanopathies' mainly involving heart and skeletal muscles. Moreover, the well-known disease called Hutchinson-Gilford Progeria Syndrome due to extensive mutations in LMNA gene, in addition to the systemic phenotype of premature aging, is characterised by the death of patients at around 13 typically for a heart attack or stroke, suggesting again the heart as the main site sensitive to Lamin A/C disfunction. Indeed, the identification of the roles of the Lamin A/C in cardiomyocytes function is a key area of exploration. One of the primary biological roles recently conferred to Lamin A/C is to affect contractile cells lineage determination and senescence. Then, in differentiated adult cardiomyocytes both the 'structural' and 'gene expression hypothesis' could explain the role of Lamin A in the function of cardiomyocytes. In fact, recent advances in the field propose that the structural weakness/stiffness of the NE, regulated by Lamin A/C amount in NE, can 'consequently' alter gene expression. © 2014 Société Française des Microscopies and Société de Biologie Cellulaire de France.

The meaning of angiographically assessed slow runoff in patients (pts) with angiographically normal coronary artery is controversial. Non-invasevely assessed absolute coronary flow reserve (CFR) in in the left anterior descending coronary artery (LAD) by Color guided pulsed-wave Doppler is a reliable parameter to assess coronary microcirculatory dysfunction (CMD). So this study aimed at assessing the value of slow runoff in predicting CMD. Results: We studied 38 consecutive pts with angiographically normal coronary artery that underwent non-invasive assessement of CFR in the LAD. We found that 9 pts out of 38 (group 1)had slow runoff and the remaining 29 had normal runoff (group 2). The CFR evaluated in the the 2 groups was not significantly different (see graph). CFR was infact, in the group 1 (Mean +/- SD) = 2,79+/- 0,8 and in the group 2= 2,89 +/- 0,7 (p= ns). In addition considering a CFR value =&lt; 2,5 as index of coronary microcirculatory dysfunction, we found CMD in 3 pts of group 1 (33%) and in 8 pts of group 2 (27%) (p=ns). The calculated sensitivity and specificity of slow runoff in predicting CMD was at 44% and 64% respectively. Conclusion: Slow runoff is not a good predictor of coronary microcirculatory dysfunction and its clinical value, if any, is uncertain and probably multifactorial.

Aim. The purpose of this study was to investigate the feasibility of contrast-enhanced ultrasound (CEUS) in the evaluation of renal artery stenosis as compared with traditional techniques: echo color Doppler (ECD) investigation and selective angiography .CEUS is a technique based on the injection of an intravascular biocompatible tracer, namely an intravenous contrast galactose microparticle suspension containing microbubbles (Levovist), that has a similar rheology to that of red blood cells, allowing quantification of renal tissue perfusion. Methods. A population of 120 hypertensive patients (82 men, mean age 55) with a systolic abdominal murmur and/or a diagnosis of poly-districtual atherosclerosis was studied by ECD and CEUS (Levovist). Selective angiography was performed in patients with renal artery stenosis demonstrated by one of the two ultrasonographic techniques. Results. Forty of the 120 patients in the study population showed renal artery stenosis at one of the two ultrasound techniques: ECD identified renal artery stenosis in 33 cases and CEUS in 38. Instead, selective angiography had detected renal artery stenosis in 38 patients, the same with renal artery stenosis diagnosed by CEUS. Thus, CEUS sensitivity, specificity and accuracy were similar to those of angiography while six false negatives and two false positives were obtained with ECD. Conclusion. Our results suggest that this renal CEUS is a promising, new, non-invasive method for screening patients with suspected renal artery stenosis. This technique appears to be superior to traditional ECD flow imaging for diagnosing renal artery stenosis and so may be an important aid in cardiovascular diagnostics.

Mutations in the Lamin A/C gene (LMNA), which encodes A-type nuclear Lamins, represent the most frequent genetic cause of dilated cardiomyopathy (DCM). This study is focused on a LMNA nonsense mutation (R321X) identified in several members of an Italian family that produces a truncated protein isoform, which co-segregates with a severe form of cardiomyopathy with poor prognosis. However, no molecular mechanisms other than nonsense mediated decay of the messenger and possible haploinsufficiency were proposed to explain DCM. Aim of this study was to gain more insights into the disease-causing mechanisms induced by the expression of R321X at cellular level. We detected the expression of R321X by Western blotting from whole lysate of a mutation carrier heart biopsy. When expressed in HEK293 cells, GFP- (or mCherry)-tagged R321X mislocalized in the endoplasmic reticulum (ER) inducing the PERK-CHOP axis of the ER stress response. Of note, confocal microscopy showed phosphorylation of PERK in sections of the mutation carrier heart biopsy. ER mislocalization of mCherry-R321X also induced impaired ER Ca(2+) handling, reduced capacitative Ca(2+) entry at the plasma membrane and abnormal nuclear Ca(2+) dynamics. In addition, expression of R321X by itself increased the apoptosis rate. In conclusion, R321X is the first LMNA mutant identified to date, which mislocalizes into the ER affecting cellular homeostasis mechanisms not strictly related to nuclear functions.

Background. Indications to the implantable cardioverter-defibrillator (ICD) have been expanded in the last decade, including patients suffering from heart disease with or without functional disorders. Accordingly, the increasing number of patients with ICD is posing relevant legal implications. Currently, the Medical Committee that evaluates the legal criteria for disability is employing guidelines referring only to pacemaker devices and not to ICD. The aim of this study was to propose new indications for patients with ICD to replace the current criteria. Methods. The study included 219 patients (83%male, mean age 63 years) with ICD who were administered an anonymous questionnaire to evaluate the presence of any disability. Most patients were suffering from ischemic or non-ischemic dilated heart disease (41% and 34%, respectively). Single- and dual-chamber ICD (72%) were more frequently implanted compared to biventricular ICD (28%). Results. A higher percentage of disability was found in older patients (69±14 years) with ischemic heart disease (61%) and single- or dual-chamber ICD before ICD implantation. Conversely, a lower percentage of disability was found in younger patients (53±15 years), active workers (44%), without ischemic or non-ischemic dilated heart disease (36%), and with a lower number of biventricular ICD (22%) after ICD implantation. Conclusions. Overall, these data show that disability is currently recognized because of the presence of ICD rather than the underlying heart disease. We propose, therefore, new criteria that include the impact of the underlying heart disease for a better evaluation of disability in patients with ICD.

Background: Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting. Objective: The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions. Methods: In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year. Results: The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25th-75th percentile, 1-4) days vs 29 (25th-75th percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65). Conclusions: RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits.

Background: With the advent of remote monitoring, current models of implantable cardioverter defibrillators (ICDs) have the possibility of sending automatic alert messages that allow early diagnosis of events such as lung fluid overload, atrial fibrillation and device integrity issues. Timely treatment of these events has the potential to improve patient outcome, but this has not as yet been proven. Methods: The MORE-CARE study is a multicenter randomized controlled trial evaluating the efficacy of advanced device diagnostics and remote monitoring in improving the outcome of patients with biventricular ICDs. Up to 1720 patients with a standard indication for a biventricular ICD will be randomized to standard in-office follow-up, or to a remote monitoring strategy using the CareLink network and involving automatic alerts for lung fluid overload, atrial fibrillation, and device integrity issues. The first phase aims at evaluating the delay between an alert event, and clinical action to the event. The second phase of the study will evaluate whether the remote monitoring strategy results in a significant reduction of a combined end point of total mortality or cardiovascular and device-related hospitalization. The duration of the study will be event-driven due to its sequential design. Conclusion: MORE-CARE will evaluate the efficacy of remote monitoring for improving patient outcome in patients implanted with a biventricular ICD.

Abstract AIMS: The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). METHODS AND RESULTS: We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. CONCLUSIONS: Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis

AIMS: The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). METHODS AND RESULTS: We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. CONCLUSIONS: Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis.

Background. The meaning of the slow coronary flow phenomenon, (SCF) as visualized in patients (pts) with angiographically normal coronary arteries, is controversial. Non-invasively assessed absolute coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) by transthoracic colour guided pulsed-wave Doppler is a reliable parameter to assess coronary microcirculatory dysfunction (CMD). This study aimed to assess the value of SCF in predicting CMD. Methods. Seventy-three consecutive pts with angiographically normal coronary arteries underwent both non-invasive assessment of CFR in the LAD and TIMI frame count assessment of coronary contrast runoff. Results. We found that 13 pts out of 73 (group 1) had SCF and the remaining 60 had normal runoff (group 2). The CFR evaluated in both groups was not significantly different (see graph). CFR was 2.86+ 0.7 (Mean + SD) in group 1, and 2.89 + 0.8 in group 2 (p= ns). In addition, considering a CFR value &lt; 2.5 as an index of coronary microcirculatory dysfunction, we found CMD in 5 pts of group 1 (38%) and in 20 pts of group 2 (33%) (p=ns). The calculated sensitivity and specificity of SCF in predicting CMD was 20% (5/20) and 83% (40/48) respectively (p=ns). Conclusion: The slow coronary flow phenomenon is not a good predictor of coronary microcirculatory dysfunction as assessed by absolute CFR. It might reflect, however, only a resting microcirculatory abnormality and probably remains a multifactorial phenomenon.

Background: Heart failure(HF) and atrial fibrillation(AF) frequently coexist in the same patient and are associated with increased mortality and frequent hospitalizations. As the concomitance of AF and HF is often associated with a poor prognosis, the prompt treatment of AF in HF patients may significantly improve outcome.Methods/design: Recent implantable cardiac resynchronization (CRT) devices allow electrical therapies to treat AF automatically. TRADE-HF (trial registration: NCT00345592; http://www.clinicaltrials.gov) is a prospective, randomized, double arm study aimed at demonstrating the efficacy of an automatic, device-based therapy for treatment of atrial tachycardia and fibrillation(AT/AF) in patients indicated for CRT. The study compares automatic electrical therapy to a traditional more usual treatment of AT/AF: the goal is to demonstrate a reduction in a combined endpoint of unplanned hospitalizations for cardiac reasons, death from cardiovascular causes or permanent AF when using automatic atrial therapy as compared to the traditional approach involving hospitalization for symptoms and in-hospital treatment of AT/AF.Discussion: CRT pacemaker with the additional ability to convert AF as well as ventricular arrhythmias may play a simultaneous role in rhythm control and HF treatment. The value of the systematic implantation of CRT ICDs with the capacity to deliver atrial therapy in HF patients at risk of AF has not yet been explored. The TRADE-HF study will assess in CRT patients whether a strategy based on automatic management of atrial arrhythmias might be a valuable option to reduce the number of hospital admission and to reduce the progression the arrhythmia to a permanent form.Trial registration: NCT00345592