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Background: Switching between antiarrhythmic drugs is timed to minimize arrhythmia recurrence and adverse reactions. Dronedarone and amiodarone have similar electrophysiological profiles; however, little is known about the optimal timing of switching, given the long half-life of amiodarone. Methods: The ARTEMIS atrial fibrillation (AF) Loading and Long-term studies evaluated switching patients with paroxysmal/persistent AF from amiodarone to dronedarone. Patients were randomized based on the timing of the switch: immediate, after a 2-week, or after a 4-week washout of amiodarone. Patients who did not convert to sinus rhythm after amiodarone loading underwent electrical cardioversion. The primary objectives were, for the Loading study, to evaluate recurrence of AF ≤60 days; and for the Long-term study, to profile the pharmacokinetics of dronedarone and its metabolite according to different timings of dronedarone initiation. Results: In ARTEMIS AF Loading, 176 were randomized (planned 768) after a 28 ± 2 days load of oral amiodarone. Atrial fibrillation recurrence trended less in the immediate switch versus 4-week washout group (hazard ratio [HR] = 0.65 [97.5% CI: 0.34-1.23]; P = .14) and in the 2-week washout versus the 4-week washout group (HR = 0.75 [97.5% CI: 0.41-1.37]; P = .32). In ARTEMIS AF Long-term, 108 patients were randomized (planned 105). Pharmacokinetic analyses (n = 97) showed no significant differences for dronedarone/SR35021 exposures in the 3 groups. Conclusion: The trial was terminated early due to poor recruitment and so our findings are limited by low numbers. However, immediate switching from amiodarone to dronedarone appeared to be well tolerated and safe.

Objectives The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy. Methods Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates. Results Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714–0.846), positive predictive value 0.636 (0.556–0.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636–0.8) and positive predictive value of 0.714 (0.636–0.8). Conclusion In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension.

Mild cognitive impairment (MCI) is a heterogeneous syndrome with two main clinical subtypes, amnestic (aMCI) and non-amnestic (naMCI). The analysis of heart rate variability (HRV) is a tool to assess autonomic function. Cognitive and autonomic processes are linked via the central autonomic network. Autonomic dysfunction entails several adverse outcomes. However, very few studies have investigated autonomic function in MCI and none have considered MCI subtypes or the relationship of HRV indices with different cognitive domains and structural brain damage. We assessed autonomic function during an active orthostatic challenge in 253 oupatients aged ≥ 65, [n = 82 aMCI, n = 93 naMCI, n = 78 cognitively normal (CN), neuropsychologically tested] with power spectral analysis of HRV. We used visual rating scales to grade cerebrovascular burden and hippocampal/insular atrophy (HA/IA) on neuroimaging. Only aMCI showed a blunted response to orthostasis. Postural changes in normalised low frequency (LF) power and in the LF to high frequency ratio correlated with a memory test (positively) and HA/IA (negatively) in aMCI, and with attention/executive function tests (negatively) and cerebrovascular burden (positively) in naMCI. These results substantiate the view that the ANS is differentially impaired in aMCI and naMCI, consistently with the neuroanatomic substrate of Alzheimer's and small-vessel subcortical ischaemic disease.

AIMS The efficacy of a telephone support program in chronic heart failure has been questioned particularly when considering short-term follow-up. This study is aimed to assess the impact of the HeartNetCare telephone support program in chronic heart failure within 18 months of observation and to verify a possible effect of a learning-to-care curve on outcome. METHODS We retrospectively compared a cohort of 269 chronic heart failure patients included in HeartNetCare program with 200 patients receiving usual care as a control group. All-cause death and hospitalization for heart failure or implantation of left ventricular assist device were the primary composite outcome. Secondary endpoints were the changes in left ventricular ejection fraction and in New York Heart Association (NYHA) functional class. Outcome data were also analyzed in relation to the time of enrollment from program initiation. RESULTS At baseline, HeartNetCare group showed lower ejection fraction and higher NYHA class. At the follow-up, 59 HeartNetCare patients (21.9%) and 49 usual care patients (24.5%) reached the primary endpoint (P = 0.51). After 18 months of follow-up, HeartNetCare patients improved ejection fraction and NYHA class compared with the usual care patients (P

Objectives: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard. Background: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation. Methods: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses. Results: In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv. Conclusions: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard.

Background Chagas disease (ChD) may lead to life-threatening heart disease, including malignant ventricular arrhythmias. The use of implantable cardioverter defibrillators (ICDs) has become the main therapeutic strategy for secondary prevention of SCD in Chagas disease (ChD). Microvolt T-wave alternans (MTWA) is a direct measure of ventricular repolarization instability and has emerged as a potentially useful way of determining arrhythmia vulnerability. However, this methodology has not been evaluated in patients with ChD. Objective To evaluate the predictive value of MTWA testing for appropriate therapy or death in ChD patients with ICDs. Methods This prospective study included consecutive patients who received ICD implantations in a Brazilian tertiary referral center. Results Seventy-two patients were followed for a median time of 422 (range 294–642) days. Thirty-three patients had ChD. The MTWA was non-negative (positive or indeterminate) in 27 (81.8%) of ChD patients. The combined primary outcome (appropriate ICD therapy or death) occurred in 29 patients (40.3%); 17 out 33 ChD patients presented the primary outcome. There was a statistically significant difference in event-free survival between ChD patients with negative and non-negative MTWA results ( p =0.02). Non-negative MTWA tests nearly triple the risk of appropriate ICD therapy or death (HR=2.7, 95% CI: 1.7–4.4, p =0.01) in patients with ChD and was the only variable associated with outcomes. The sensitivity and the negative predictive value was 100% in ChD patients. Conclusions MTWA may be useful in recognizing high-risk ICD patients who may require adjunctive therapies with antiarrhythmic drugs or catheter ablation.

The PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Antiplatelet Therapy (PRECISE-DAPT) score has been validated to predict bleeding complications in patients undergoing stent implantation and dual antiplatelet therapy. This score does not include the platelet count (PC), which has been shown to be an independent marker of mortality in patients with acute coronary syndrome (ACS). We assessed the role of the PRECISE-DAPT score calculated on admission for mortality risk prediction and evaluated whether the predictive accuracy of this score improved by adding the PC. In a retrospective cohort study of 1000 patients with ACS, after adjustment for relevant covariates, a PRECISE-DAPT score ≥25 was independently associated with mortality (hazard ratio [HR]: 7.91; 95% confidence interval [CI]: 4.37-14.30). When this score was combined with PC, compared to patients with PRECISE-DAPT 9/L, the adjusted HR was 7.2 (95% CI 2.4-21.6) for those with PRECISE-DAPT 9/L; 10.7 (95% CI: 5.2-21.9) for those with PRECISE-DAPT ≥25 and PC ≥150 × 109/L; and 17.9 (95% CI 7.0-45.4) for those with PRECISE-DAPT ≥25 and PC 9/L. Selecting thresholds for high-risk designation, the PRECISE-DAPT score integrated with PC had a higher prediction value, compared to the PRECISE-DAPT and Global Registry of Acute Coronary Events scores.

Coronary angioplasty (CA) is a surgical procedure meant to break the plaque and restore the blood flow in obstructed coronary arteries. It is based on inserting an inflatable balloon with a catheter in the clogged artery. When the balloon inflation is prolonged, it also provides an excellent model to investigate the electrophysiological changes due to early ischemia. In this work, we tested whether early cardiac ischemia induced by prolonged balloon inflations might lead to changes in spatial heterogeneity of ventricular repolarization (SHVR), as measured by the V-index on the 12-lead ECG. The metric was recently shown to significantly improve the ECG sensitivity for the diagnosis of non-ST elevation myocardial infarction, in patients presenting to the emergency department. The analysis was retrospectively performed on the data of 104 patients who underwent prolonged CA (STAFF III dataset). The V-index was estimated before, during and post-occlusion (limiting the analysis to the first inflation). Successively, it was quantified on short 90 s overlapping windows, during occlusion, to assess the time evolution of SHVR. V-index values estimated during occlusion were significantly larger (median: 6.2 ms, p; 0.05) than baseline room values. Also, pre- and post-occlusion values did not differ (p0.05), suggesting a complete recovery after CA. SHVR progressively increased during the occlusion with respect to baseline (median reaching 55.6 ms vs 34.2 ms). In conclusion, the V-index detected changes in SHVR due to early-stage cardiac ischemia.

Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three-dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image-guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography.

Background Critical limb ischemia (CLI) is a major health problem with no adequate treatment. Since CLI is characterized by insufficient tissue vascularization, efforts have focused on the discovery of novel angiogenic factors. Cyclophilin A (CyPA) is an immunophilin that has been shown to promote angiogenesis in vitro and to enhance bone marrow (BM) cell mobilization in vivo . However, its potential as an angiogenic factor in CLI is still unknown. Thus, this study aimed to evaluate whether CyPA might induce neo-angiogenesis in ischemic tissues. Methods and results Wild-type C57Bl/6j mice underwent acute hind-limb ischemia (HLI) and received a single intramuscular administration of recombinant CyPA or saline. Limb perfusion, capillary density and arteriole number in adductor muscles were significantly increased after CyPA treatment. Interestingly, BM-derived CD117 + cell recruitment was significantly higher in ischemic adductor tissue of mice treated with CyPA versus saline. Therefore, the effect of CyPA on isolated BM-derived CD117 + cells in vitro was evaluated. Low concentrations of CyPA stimulated CD117 + cell proliferation while high concentrations promoted cell death. Moreover, CyPA enhanced CD117 + cell adhesion and migration in a dose-dependent manner. Mechanistic studies revealed that CyPA up-regulated CXCR4 in CD117 + cells and in adductor muscles after ischemia. Additionally, SDF-1/CXCR4 axis inhibition by the CXCR4 antagonist AMD3100 decreased CyPA-mediated CD117 + cell recruitment in the ischemic limb. Conclusion CyPA induces neo-angiogenesis by recruiting BM-derived CD117 + cell into ischemic tissues, at least in part, through SDF-1/CXCR4 axis.

Contrast-induced acute kidney injury (CI-AKI) is associated with significantly increased mortality after primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). The prognostic value of CI-AKI depends on the definitions used to define it. We compare the predictive accuracy of long-term mortality of two definitions of CI-AKI on consecutive patients undergoing pPCI for STEMI.Incidence, risk factors and long-term prognosis of CI-AKI were assessed according to two different definitions: the first as an increase in serum creatinine ≥ 25% or ≥ 0.5 mg/dl from baseline within 72 h after pPCI (contrast-induced nephropathy (CIN) criteria), the second one according to Acute Kidney Injury Network (AKIN) classification system.A total of 402 patients were enrolled. The median follow-up period was 12 ± 4 months. Long-term mortality rate was 9.5%. Independent predictors of long-term mortality were: older age, basal renal impairment, left ventricular ejection fraction40%, in-hospital major bleedings and CI-AKI. A significant correlation was found between mortality and CI-AKI as assessed by both CIN (HR 4.84, 95% CI: 2.56-9.16, p=0.000) and AKIN (HR 9.70, 95% CI: 5.12-18.37, p=0.000) definitions. The area under the receiver operating curve was significantly larger for predicting mortality with AKIN classification than with CIN criteria (0.7984 versus 0.7759; p=0.0331).In patients with STEMI treated by pPCI, CI-AKI is a frequent complication irrespective of the criteria used for its definition. AKIN, however, seems to provide a better accuracy in predicting long-term mortality than CIN criteria.

We describe the echocardiographic finding of a 35-year-old pregnant woman, referred for a clinical consultation at our institution because of congestive heart failure. She underwent echocardiography with only little information about a history of cardiac surgery during infancy. At the first sight, parasternal long axis view demonstrates normal structures, but on the apical view we diagnosed a very rare condition with typical imaging findings: Criss Cross heart.

The coexistence of an atrial septal defect and a prominent eustachian valve is a rare congenital anomaly, rarely reported in literature. Differentiation between a giant eustachian valve and cor triatriatum dexter can be difficult. A case of a large atrial septal defect associated with cor triatriatum dexter diagnosed by echocardiography in an asymptomatic woman is reported. A watchful waiting strategy was adopted.

Background The purpose of the study was to determine the long-term prognostic value of normal adenosine stress cardiac magnetic resonance imaging (CMR) in patients referred for evaluation of myocardial ischemia. Methods We reviewed 300 consecutive patients (age 65 ± 11 years, 74% male) with suspected or known coronary disease and normal wall motion who had undergone adenosine stress CMR negative for ischemia and scar. Most patients were at intermediate risk of coronary artery disease. The end points studied were all causes of mortality and major adverse cardiac events, including cardiac death, myocardial infarction, revascularization, and hospitalization for unstable angina. Results During a mean follow-up of 5.5 years (mean = 5.4 ± 1.1), 16 patients died because of various causes (cardiac death in 5 patients). Three patients had a nonfatal myocardial infarction, 7 patients were hospitalized for revascularization, and 11 were medically treated for unstable angina. The annual cardiac event rate was 1.3% (0.78% in the first 3 years and 1.9% between the fourth and sixth years). The predictors of major adverse cardiac events in a multivariate analysis model were as follows: advanced age (hazard ratio [HR] 1.15, 95% confidence interval [95% CI] 1.02-1.30), diabetes (HR 17.5, 95% CI 2.2-140), and the habit of smoking (HR 5.9, 95% CI 1.0-35.5). For all causes of mortality, the only predictor was diabetes (HR 11.4, 95% CI 1.76-74.2). Patients with normal stress CMR had an excellent outcome during the 3 years after the study. The cardiac event rate was higher between the fourth and sixth years. Conclusion Over a 5.5-year period, a low event rate and excellent prognosis occurred in patients with normal adenosine stress CMR. Low- to intermediate-risk patients with a normal CMR are at low risk for subsequent cardiac events.

Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients. Methods Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at enrolment, on the morning of cardiac surgery, at end surgery, and 2 days postsurgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 s, centrally adjudicated and confirmed electrocardiographically. Results Higher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT-proBNP peaked on postoperative day 2 (2172 [1238–3758] ng/L, median [Q1–Q3]), while hs-cTnT peaked at the end of surgery (373 [188–660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (P > 0·05). Concentrations of NT-proBNP or hs-cTnT, on the morning of surgery, or changes in their level between morning of surgery and postsurgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics. Conclusion Among patients undergoing cardiac surgery, NT-proBNP and hs-cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.

The aim of the present study is to evaluate the additional value of systolic wall thickening to myocardial perfusion in diagnosing myocardial stunning in patients with angiography proven coronary artery disease. We selected 91 ischemic patients (82 males; mean age 59.7 ± 10.3) with CAD documented by angiography. Ischemia was defined as a summed difference score ≥5. All patients underwent a 2-day gated perfusion SPECT protocol. The patients received a dose of 740 MBq of 99mTc-tetrofosmin after stress and at rest. Treadmill maximal exercise tests were performed on all patients. The post-stress LVEF was significantly lower than rest LVEF (48.1% ± 10.3% vs 50.3% ± 10.7%; P = .0001). The wall thickening summed difference score was 4.44 ± 4.13 (P = .0001). At a multivariate regression analysis, only WT-SDS as independent variable was significantly correlated with myocardial ischemia (SDS). We also divided patients according to SDS in those with mild (SDS

A 56-year-old man presented to the Outpatient Cardiology Unit for dyspnea that had been lasting 6 months and an occasional episode of cold perspiration on climbing a flight of stairs. In the suspicion of coronary artery disease, he was prescribed a complete blood panel, an echocardiogram and a treadmill stress test. The echocardiogram, performed as late as 78 days after the first evaluation and only by chance scheduled 2 days before the stress test, enabled a diagnosis of left atrial myxoma for which the patient successfully underwent cardiac surgery. The authors discuss the aspecific and potentially misleading nature of myxoma symptoms and highlight the latency between cardiological evaluation and diagnostic echocardiography.

Undiagnosed atrial fibrillation (AF) patients are at high risk of cardioembolic stroke or other complications. The aim of this study was to analyze the blood volume pulse (BVP) signals obtained from a wristband device and develop an algorithm for discriminating AF from normal sinus rhythm (NSR) or from other arrhythmias (ARR).Thirty patients with AF, 9 with ARR and 31 in NSR were included in the study. The recordings were obtained at rest from Empatica E4 wristband device and lasted 10 min. The analysis, on a 2 min segment, included spectral, variability and irregularity analysis performed on the inter-diastolic interval series, and similarity analysis performed on the BVP signal. Main results and Significance: Variability parameters were the highest in AF, the lowest in NSR and intermediate for ARR, as an example pNN50 values were, respectively, [Formula: see text], [Formula: see text], [Formula: see text] (p 0.05). The similarity parameters were the highest in NSR, the lowest in AF and intermediate for ARR, as an example using a threshold for assessing similarity of [Formula: see text]: [Formula: see text], [Formula: see text], [Formula: see text], all p 0.05. The rhythm classification was preceded by over-sampling (using synthetic minority over-sampling technique) the class of ARR, being it the smallest class. Then, the features selection was performed (using the sequential forward floating search algorithm) which identified two variability parameters (pNN70 and pNN40) as the best selection. The classification by the k-nearest neighbor classifier reached an accuracy of about 0.9 for NSR and AF, and 0.8 for ARR. Using pNN70 and pNN40, the specificity for the three rhythms was Spnsr = 0.928, Spaf = 0.963, Sparr = 0.768, while the sensitivity was Spnsr = 0.773, Spaf = 0.754, Sparr = 0.758.

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice has revolutionized the prevention and the therapeutic approaches to thromboembolic events in patients with nonvalvular atrial fibrillation and represents with no doubts one of the most remarkable advances in the history of cardiovascular medicine over the last years. NOACs beyond a comparable efficacy with vitamin K antagonists allow to overcome the limitations of this last category of drugs owing to their less drug to drug interactions and a predictable anticoagulant effect that allows a fixed dose administration without the need for continuous monitoring. However, the penetration of NOACs into the Italian market is still lower than predicted with respect to their use in other European countries.The aim of this review is to critically analyze the reasons behind this attitude through the adoption of the nominal group technique, a methodology that permits to reach an official consensus.

Aims Dynamics of cardiovascular series may be explored with non-linear techniques. It is unknown if the arterial pressure irregularity commonly observed in patients with atrial fibrillation (AF) might be further increased by a sympathetic stimulus such as orthostatic tilt. Methods and results Twenty patients (62 ± 14 years, 15 men) were recruited for the study. Continuous beat-to-beat non-invasive arterial pressure was acquired at rest and during a passive orthostatic stimulus (‘tilt test’). Systolic (SAP) and diastolic (DAP) arterial pressure series of 300 samples were analysed in both conditions. Approximate (ApEn) and sample entropy (SampEn) were computed, as irregularity measures. Equivalent metrics (ApEnAR and SampEnAR) derived from an autoregressive model of the series were also obtained through numerical simulations, to further elucidate the non-linear mechanisms present in the series. In 11 patients (Group A), SAP significantly increased during tilt (from 103 ± 13 to 114 ± 17 mmHg, P < 0.001 rest vs. tilt), whereas in 9 patients (Group B) SAP remained almost unchanged (SAP: 110 ± 18 vs. 106 ± 19 mmHg, rest vs. tilt). No clinical differences were found between Groups A and B. When analysing Group A, all irregularity measures significantly increased in SAP (ApEn: 1.75 ± 0.20 vs. 1.88 ± 0.16, P < 0.05; SampEn: 1.71 ± 0.30 vs. 1.88 ± 0.27, P < 0.05; ApEnAR: 1.87 ± 0.20 vs. 1.96 ± 0.18, P < 0.05; SampEnAR: 1.94 ± 0.27 vs. 2.06 ± 0.18, P < 0.05; rest vs. tilt), whereas no differences were found in DAP series. No significant differences were found in Group B for either SAP or DAP. Conclusion The alterations of SAP during tilt in AF patients are not uniform and seem associated with different regularity patterns. The pressor response to sympathetic stimulation was also associated with an increase of SAP series irregularity.

Propranolol is becoming the treatment of choice for complicated infantile hemangioma. We report here data on peripheral blood flow, O2-saturation, electrocardiographic PR-interval, left ventricular function, blood pressure and heart rate that were assessed before and during treatment for ≥4 weeks with propranolol 2 mg/kg of body weight daily in 67 infants 2-saturation, electrocardiographic PR-interval and left ventricular fractional shortening or ejection fraction. Absolute blood pressure levels were similar without and with propranolol. However, age-adjusted centile levels for both systolic and diastolic levels were significantly lower while on propranolol. The heart rate was significantly lower both when expressed as absolute value and when expressed as age-adjusted centile on treatment with propranolol. In conclusion, propranolol 2 mg/kg of body weight daily causes a statistically though not clinically relevant decrease in blood pressure and heart rate in cardially healthy infants affected by infantile hemangioma. Temporary discontinuation during acute febrile illnesses and during diarrheal diseases should be considered to prevent excessive hypotension.

The exact mechanisms of sudden unexpected death in epilepsy remain elusive, despite there is consensus that SUDEP is associated with severe derangements in the autonomic control to vital functions as breathing and heart rate regulation. Heart rate variability (HRV) has been advocated as biomarker of autonomic control to the heart. Cardiac dysautonomia has been found in diseases where other branches of the autonomous nervous system are damaged, as Parkinson disease and multiple system atrophy. In this perspective, an impaired HRV not only is a risk factor for sudden cardiac death mediated by arrhythmias, but also a potential biomarker for monitoring a progressive decline of the autonomous nervous system. This slope may lead to an acute imbalance of the regulatory pathways of vital functions after seizure and then to SUDEP.

Cardiac magnetic resonance (CMR) is useful for the diagnosis of left ventricular noncompaction (LVNC). However, there are limited data regarding its prognostic value.The goal of this study was to evaluate the prognostic relevance of CMR findings in patients with LVNC.A total of 113 patients with an echocardiographic diagnosis of LVNC underwent CMR at 5 referral centers. CMR diagnostic criterion of LVNC (noncompacted/compacted ratio2.3 in end-diastole) was confirmed in all patients. We performed left ventricular (LV) and right ventricular quantitative analysis and late gadolinium enhancement (LGE) assessments and analyzed the following LVNC diagnostic criteria: left ventricular noncompacted myocardial mass (LV-ncMM)20% and25%, total LV-ncMM index15 g/mAt a mean follow-up of 48 ± 24 months, cardiac events (CEs) occurred in 36 patients (16 heart failure hospitalizations, 10 ventricular arrhythmias, 5 cardiac deaths, and 5 thromboembolic events). LV dilation, impaired LV ejection fraction, and LV-ncMM20% was significantly more frequent in patients with CEs. LV fibrosis was detected by using LGE in 11 cases. CMR predictors of CEs were LV dilation and LGE. LGE was associated with improved prediction of CEs, compared with clinical data and CMR functional parameters in all 3 models. No CEs occurred in patients without dilated cardiomyopathy and/or LGE.In patients with LVNC evaluated by using CMR, the degree of LV trabeculation seems to have no prognostic impact over and above LV dilation, LV systolic dysfunction, and presence of LGE.

Background— Computed tomography coronary angiography (cTCA) and stress cardiac magnetic resonance (stress-CMR) are suitable tools for diagnosing obstructive coronary artery disease in symptomatic patients with previous history of revascularization. However, performance appraisal of noninvasive tests must take in account the consequent diagnostic testing, invasive procedures, clinical outcomes, radiation exposure, and cumulative costs rather than their diagnostic accuracy only. We aimed to compare an anatomic (cTCA) versus a functional (stress-CMR) strategy in symptomatic patients with previous myocardial revascularization procedures. Methods and Results— Six hundred patients with chest pain and previous revascularization included in a prospective observational registry and evaluated by clinically indicated cTCA (n=300, mean age 68.2±9.7 years, male 255) or stress-CMR (n=300, mean age 67.6±9.7 years, male 263) were enrolled and followed-up in terms of subsequent noninvasive tests, invasive coronary angiography, revascularization procedures, cumulative effective radiation dose, major adverse cardiac events, defined as a composite end point of nonfatal myocardial infarction and cardiac death, and medical costs. The mean follow-up for cTCA and stress-CMR groups was similar (773.6±345 versus 752.8±291 days; P =0.21). Compared with stress-CMR, cTCA was associated with a higher rate of subsequent noninvasive tests (28% versus 17%; P =0.0009), invasive coronary angiography (31% versus 20%; P =0.0009), and revascularization procedures (24% versus 16%; P =0.007). Stress-CMR strategy was associated with a significant reduction of radiation exposure and cumulative costs (59% and 24%, respectively; P P P Conclusions— Compared with cTCA, stress-CMR is more cost-effective in symptomatic revascularized patients.

Background Subclinical inflammation and atrial stretch have been recognized as important contributors to atrial fibrillation (AF) onset and perpetuation. The aim of the study was to compare the predictive role of serum inflammatory markers (serum amyloid A [SAA], and C-reactive protein [CRP]) and N-terminal pro brain natriuretic peptide (NT-proBNP) an indice of atrial strain in relation to subacute arrhythmic recurrence rate in patients with persistent AF and normal left ventricular ejection fraction (LVEF). Methods We studied 57 patients with a mean LVEF of 58.7 ± 6%. NT-proBNP, SAA and CRP levels were determined few hours before electrical cardioversion and 3 weeks after cardioversion. Results Subacute AF recurrences were documented in 19 (33 %) patients. Whereas NT-proBNP levels did not predict arrhythmic outcome, higher SAA (> 6.16-6.19 mg/L) and CRP levels (> 2.99-3.10 mg/L) were significantly associated with AF recurrences (odds ratio [OR], 5.39; 95% confidence interval [CI], 1.59-18.26; P = 0.007 and OR, 14.93; 95% CI, 3.90-57.19; P P = 0.009) and high sensitivity CRP (OR, 42.03; 95% CI, 4.83-365.45; P = 0.001) through the multivariate logistic regression analysis show an independent role in predicting the AF recurrence with a sensitivity of 100% (38/38) and a specificity of 52.6% (10/19). Conclusions The present study demonstrates that in patients with persistent AF and preserved LVEF, SAA and CRP levels are independent predictors of AF subacute recurrence rate, whereas NT-proBNP, not associated with arrhythmic outcome, reflects the hemodynamic alterations secondary to arrhythmia presence. The simultaneous determination of SAA and high sensitivity CRP has a very high sensitivity (100%) in predicting the AF recurrence.

Antiarrhythmic Effect of Acupuncture. Introduction: In traditional Chinese medicine, stimulation of the Neiguan spot has been utilized to treat palpitations. We evaluated whether acupuncture might prevent or reduce the rate of arrhythmia recurrences in patients with persistent atrial fibrillation (AF). Methods and Results: We studied 80 patients with persistent AF after restoring sinus rhythm with electrical cardioversion. Twenty-six subjects who were already on amiodarone treatment constituted the AMIO reference group. The remaining patients were randomly allocated to receive acupuncture (ACU group, n = 17), sham acupuncture (ACU-sham group, n = 13), or neither acupuncture nor antiarrhythmic therapy (CONTROL group, n = 24). Patients in the ACU and ACU-sham groups attended 10 acupuncture sessions on a once-a-week basis. Only in the former group the Neiguan, Shenmen, and Xinshu spots were punctured. During a 12-month follow-up, AF recurred in 35 patients. Cumulative AF recurrence rates in the AMIO, ACU, ACU-sham, and CONTROL patients were 27%, 35%, 69%, and 54%, respectively (P = 0.0075, log-rank test). Ejection fraction (P = 0.0005), hypertension (0.0293), and left atrial diameter (P = 0.0361) were also significantly associated with AF recurrence. Compared with AMIO group, recurrence rate was similar in ACU patients (hazard ratio: 1.15, 95% CI: 0.38–3.49; P = 0.801) but significantly higher in ACU-sham and CONTROL patients (3.77, 1.39–10; P = 0.009 and 3.15, 1.23–8.06; P = 0.017, respectively) after adjustment for ejection fraction, hypertension, and left atrial diameter using Cox modeling. Conclusion: Our data indicate that acupuncture treatment prevents arrhythmic recurrences after cardioversion in patients with persistent AF. This minimally invasive procedure was safe and well tolerated. (J Cardiovasc Electrophysiol, Vol. 22, pp. 241-247, March 2011)

Our aim was to evaluate the Standard Deviation of Normal–Normal (SDNN) interbeat interval as a risk marker in left ventricular systolic dysfunction (LVSD) patients through a meta-analysis. We searched PubMed for studies that evaluated SDNN as a predictor of all-cause-death, cardiac death, transplantation, and progressive clinical deterioration using a search strategy validated for MEDLINE. Mean values and SD for SDNN in sixteen studies included were 115±48 ms in survivors versus 87±40 ms in non-survivors, resulting in a statistically significant standardized mean difference (0.594, 95%CI 0.385 to 0.803). In conclusion, SDNN may be a useful prognostic marker in LVSD. Additional studies must evaluate if SDNN may be used to subsidize therapeutic decisions.

Background Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm (SR). Identifying risk factors for recurrence may help define the best strategy for secondary prevention. Methods The GISSI-AF trial enrolled 1,442 patients in SR with at least 2 documented AF episodes in the previous 6 months or after cardioversion in the last 2 weeks. Patients were randomized to valsartan or placebo; all other treatments for AF or underlying heart diseases were allowed. Primary end points were time to first recurrence of AF and proportion of patients with >1 AF episode during 1-year follow-up. We evaluated clinical and electrocardiographic baseline characteristics of all patients to identify independent predictors for AF recurrence using a Cox multivariable model. Results Risk factors for AF recurrence were a history of 2 or more AF episodes in the previous 6 months, independent of the modality of SR restoration, spontaneous (HR 1.42, 95% CI 1.14-1.77, P = .002), or by cardioversion (HR 1.19, 95% CI 1.01-1.40, P = .038), and a lower heart rate during SR (HR 0.99, 95% CI 0.99-1.00, P = .052). The risk factors were the same for >1 AF recurrence. Patients treated with amiodarone had a lower risk for both end points ( P P = .017), whereas those on diuretics had a greater risk ( P = .009 and P = .003). Conclusions In the GISSI-AF study population, AF history had significant prognostic value independent of the modality of SR restoration. Amiodarone and diuretic treatment affected the rate of AF recurrence.

Atrial fibrillation (AF) is characterized by desynchronization of atrial electrical activity causing a consequent irregular ventricular response. In AF, the beat-to-beat variation of blood pressure is increased because of variations in filling time and contractility. However, only a few studies have analyzed short-term blood pressure variations in AF, and we have recently observed a harmonic low-frequency (LF) component in systolic arterial pressure (SAP) during AF. Aim of the present study is to propose a method to verify the reliability of the spectral component found in SAP series, based on the position of the poles of the autoregressive spectral decomposition in the z-plane. In particular, 1,000 random permutations of the series allowed the definition of an area in the z-plane where poles from random process are likely to occur. Poles lying outside this area are considered as reliable oscillations. We tested the method on 53 recordings obtained at rest from patients with persistent AF. LF component was found in, respectively, 51 and 43 recordings in SAP and RR series. High-frequency (HF) component was found in all the recordings for both SAP and RR series. Using the proposed test, the percentage of reliable components in LF and HF bands was 80 and 38 in SAP series, and 20 and 18 in RR series. We concluded that, at variance with RR ones, SAP LF components are likely to represent true physiological oscillations.

Background Contrast-induced nephropathy (CIN) is the third cause of acute deterioration of renal function in hospitalized patients. Hypothesis The purpose of the study was to compare the efficacy of saline infusion, saline infusion plus N-acetylcysteine (NAC), and sodium bicarbonate (SB) infusion to prevent CIN in patients undergoing coronary angiography and/or percutaneous coronary intervention. Methods We prospectively studied 156 patients with a baseline creatinine level ≥ 1.2 mg/dL. The primary endpoint was the development of CIN, defined as an increase in serum creatinine concentration ≥ 25% over the baseline value within 5 days from contrast exposure. Results Contrast-induced nephropathy developed in 23 patients (14.7%). Incidence of the primary endpoint was similar in the 3 groups of treatment, occurring in 7 patients (14%) in the saline infusion group, in 9 (17%) in the saline infusion plus NAC group, and in 7 (14%) in the SB infusion group. Conclusions Our findings suggest that neither the addition of NAC nor the administration of SB add further benefit in CIN prevention, compared to standard hydration with isotonic saline infusion. Copyright © 2009 Wiley Periodicals, Inc.

Atrial fibrillation (AF) is a common arrhythmia characterized by irregular ventricular response. During AF, beat-to-beat variability of arterial pressure (AP) is increased because of continuous changes in filling time, stroke volume and contractility. Only a few studies have analyzed short-term AP variability during AF but they were mainly focused on the effects of respiration. We therefore analyzed short-term systolic (S), diastolic (D) and mean (M) AP variability by autoregressive method and an FFT-based spectral estimation (Welch periodogram) in 26 patients with persistent AF before and after restoration of sinus rhythm by electrical cardioversion. A low frequency (LF) component (central frequency 0.07 ± 0.02 Hz, mean ± standard deviation) of SAP variability was observed in 23 out of 26 patients during AF. Frequency analysis of DAP and MAP also showed a LF component with a central frequency of 0.08 ± 0.03 Hz (20 patients) and 0.07 ± 0.03 Hz (25 patients), respectively. After recovery of sinus rhythm, we found significant reduction in mean SAP, DAP and MAP variability in all frequency bands. Squared coherence between SAP and heart rate variability after recovery of sinus rhythm revealed a weak and strong coupling within, respectively, LF and HF frequency bands. These data indicate that in patients with AF, in spite of an absence of rhythmical oscillation in RR interval time series, it is possible to observe a LF component in SAP, DAP and MAP variability signals. These 0.1 Hz fluctuations reflect the influence of the sympathetic fibres acting on the cardiovascular system.

Autoimmunity and dysautonomia are established features of Chagas disease (ChD) that could be related to its pathogenesis. Our objective was to assess heart rate variability (HRV) and levels of anti-M2 receptors autoantibodies in ChD patients with and without left ventricular (LV) dysfunction, in order to establish if these abnormalities occur early and concomitantly in the course of the illness.ChD patients (n=75) and healthy controls (n=14) underwent a standardized protocol including Doppler echocardiogram, Holter monitoring, HRV analysis, and measurement of anti-M2 receptors autoantibodies (ELISA). ChD patients were divided accordingly by the absence (group 1, n=45) or presence (group 2, n=30) of LV dysfunction, defined as reduced LV ejection fraction (55%) or regional wall motion abnormalities (including ventricular aneurysm).Both ChD groups displayed increased optical density values of anti-M2 cholinergic autoantibodies (Median (IQR): control=1.98(0.51); ChD 1=2.76(0.97); ChD 2=2.72(1.34), p.001) and reduced HF power of spectral analysis of HRV when compared to controls (Median (IQR) in ms2: control=1087(2284); ChD 1=286(763); ChD 2=285(763), p.001). M2 levels were significantly correlated with HF power values (r=-0.32, p=0.023), but not with LV ejection fraction.Anti-muscarinic autoantibodies and abnormal vagal modulation occur early in ChD patients, independently of the presence of LV dysfunction. Levels of antibodies against M2 muscarinic receptors were significantly and negatively correlated with HRV index HF power, suggesting an inhibitory effect of autoantibodies in vagal function.

Limited information is available on weight loss, metabolic control, cardiovascular disease and diabetic complications in morbidly obese patients undergoing gastric banding (LAGB) compared with morbidly obese patients receiving medical treatment.To assess the long-term effects of laparoscopic adjustable gastric banding (LAGB) on glucose tolerance, arterial hypertension, and cardiovascular disease and prevention of diabetic complications (retinopathy and renal function) in morbidly obese patients.University hospitals, Italy.In this retrospective study, 87 morbidly obese patients who underwent LAGB (20 with diabetes) and 87 morbidly obese patients who did not undergo surgery (36 with diabetes) for the treatment of obesity during the period 1995 to 2003 consented for re-examination after a mean (±standard deviation) period of 13.8±2.04 years. At baseline, all mobidly obese patients had a body mass index (BMI)≥35 kg/m(2) and were aged 18 to 65 years.At follow-up, LAGB patients maintained a lower weight compared with baseline values and demonstrated significant decreases in both blood pressure and heart rate measurements compared with control patients. LAGB patients also experienced greater improvement of glucose tolerance than did control patients (28% versus 10%, respectively; P.01) and reduction of insulin and homeostasis model assessment for insulin resistance. Fewer LAGB patients developed carotid plaques than did control patients (10% versus 26%, respectively; P.01). Intensification of antihypertensive therapy was required in 31% of surgery versus 60% of control patients (P.05). Among diabetic patients, improved glucose tolerance occurred in 55% of surgery patients versus 0% in the control group (P.01). In addition, insulin treatment was necessary in 9 control patients versus 0 in the surgery group (P.05), and carotid plaques occurred in 10% of LAGB patients versus 50% of control patients (P.01). Creatinine levels and the estimated glomerular filtration rate improved in LAGB diabetic patients but not in control patients (P.05).Despite a very small weight loss over the long term (i.e., 2.2 kg/m(2)), improvement of glucose tolerance persisted for long periods after LAGB, with no unfavorable effect on kidney function and retinopathy. In contrast, no effect was observed on prevention of arterial hypertension or cardiovascular disease.

Background Animal study results point to oxidative stress as a key mechanism triggering postoperative atrial fibrillation (Po AF ), yet the extent to which specific biomarkers of oxidative stress might relate to Po AF risk in humans remains speculative. Methods and Results We assessed the association of validated, fatty acid–derived oxidative stress biomarkers (F 2 ‐isoprostanes, isofurans, and F 3 ‐isoprostanes) in plasma and urine, with incident Po AF among 551 cardiac surgery patients. Biomarkers were measured at enrollment, the end of surgery, and postoperative day 2. Po AF lasting ≥30 seconds was confirmed with rhythm strip or electrocardiography and centrally adjudicated. Outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Urine level of each oxidative stress biomarker rose at the end of surgery (2‐ to 3‐fold over baseline, P 2 ‐isoprostanes and isofurans at the end of surgery were 20% and 50% higher in subjects who developed Po AF ( P ≤0.009). While baseline biomarker levels did not associate significantly with Po AF , end of surgery and postoperative day 2 isoprostanes and isofurans demonstrated relatively linear associations with Po AF . For example, the end of surgery extreme quartile multivariate adjusted OR (95% CI ) for urine isofurans and F 3 ‐isoprostanes were 1.95 (1.05 to 3.62; P for trend=0.01) and 2.10 (1.04 to 2.25, P for trend=0.04), respectively. The associations of biomarkers with Po AF varied little by demographics, surgery type, and medication use ( P ≥0.29 for each). Conclusions These novel results add to accumulating evidence supporting the likely key pathogenic role of elevated oxidative stress in Po AF . Clinical Trial Registration URL: Clinicaltrials.gov Unique identifier: NCT00970489.

Non-linear parameters were computed to assess the extent of spatial organization in the atria in terms of coupling/synchronization between electrograms recorded in different atrial sites. Recordings of 9 patients suffering from paroxysmal atrial fibrillation were tested during four clinical experimental conditions: sinus rhythm and atrial fibrillation, both before and after isoproterenol infusion, a drug mimicking adrenergic activation. Two non-linear metrics were investigated: an index of non-linear association (NLA) and a synchronization (S) index based on the cross-conditional entropy. Results evidence the presence of reduced coupling after drug infusion in both sinus rhythm and atrial fibrillation. Moreover, passing from the NLA to the S index, the capability of the parameter to capture the subtle changes due to isoproterenol administration increased.