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Background and Aims: Intensive statin therapy represents an effective option after acute coronary syndromes (ACS). Despite evidence, switching to less effective statins frequently occurs in practice. Aim of this observational study was to assess the impact of switching from intensive to moderate statin therapy on clinical outcomes after ACS., Methods and Results: A cohort of 1321 consecutive ACS patients (886 men, age 71 ± .8 years) discharged on atorvastatin 80 mg/d in a 6.5 year period was followed for 12 months after discharge. During follow-up, 557 patients (42%) were switched by primary care physicians to moderate statin therapy, either for side effects (56%) or for safety concerns (44%). No major adverse reaction was reported. Increasing age (HR 1.52 per 10-year increase, 95% CI 1.23-1.78, p=0.01), and female gender (HR 1.11, 95% CI 1.06-1.23, p=0.02) were associated with a higher probability of switch. Patients following a cardiac rehabilitation program (HR 0.64 95% CI 0.49-0.86, p=0.02) and diabetic subjects (HR 0.81, 95% CI 0.67-0.92, p=0.02) were more likely to continue atorvastatin 80 mg/d. During follow-up, a major adverse clinical event occurred in 331 patients (one-year probability 0.25, 95% CI 0.22-0.27). Multivariate analysis with Cox proportional hazards method, including statin switching as a time-dependent covariate, demonstrated that, after adjustment for demographic and clinical variables, reduction from intensive to moderate statin therapy was an independent predictor of adverse clinical outcomes (HR 2.7, 95% CI 1.7-5.1, p=0.004)., Conclusion: Switching from intensive to moderate statin therapy after ACS is associated with an increased incidence of adverse clinical events., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present study was to evaluate the smoking relapse rate among smokers who had become abstinent during admission for acute coronary syndromes. The association between smoking relapse and mortality was also analyzed. A cohort of 1,294 consecutive active smokers who had interrupted smoking after admission for acute coronary syndromes (1,018 men and 276 women, mean age 59.7 ± 12.3 years) was followed up for 12 months after the index admission. All patients received a brief in-hospital smoking cessation intervention consisting of repeated counseling sessions. During follow-up, 813 patients (62.8%) resumed regular smoking (median interval to relapse 19 days, interquartile range 9 to 76). Increasing age (hazard ratio [HR] 1.034 per year, 95% confidence interval [CI] 1.028 to 1.039, p = 0.001) and female gender (HR 1.23, 95% CI 1.09 to 1.42, p = 0.03) were independent predictors of smoking relapse. Patients enrolled in a cardiac rehabilitation program (HR 0.74, 95% CI 0.51 to 0.91, p = 0.02) and those with diabetes (HR 0.79, 95% CI 0.68 to 0.94, p = 0.03) were more likely to remain abstinent. During follow-up, 97 patients died (1-year probability of death 0.075, 95% CI 0.061 to 0.090). Multivariate analysis with the Cox proportional hazard regression method, including smoking relapse as a time-dependent covariate, demonstrated that, after adjustment for patient demographics, the clinical history features and variables related to the index event, the resumption of smoking was an independent predictor of total mortality (HR 3.1, 95% CI 1.3 to 5.7, p = 0.004). In conclusion, smoking relapse after acute coronary syndromes is associated with increased mortality, and counseling interventions should be integrated into the postdischarge support to reduce the negative effects of smoking resumption., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A standardized and evidence-based approach to the cardiological management of patients undergoing noncardiac surgery has been recently defined by Task Forces of the American Heart Association (AHA), American College of Cardiology (ACC) and the European Society of Cardiology (ESC) that published their guidelines in 2007 and 2009, respectively. Both the recommendations moved from risk indices to a practical, stepwise approach of the patient, which integrates clinical risk factors and test results with the estimated stress of the planned surgical procedure. In the present paper the main topics of the guidelines are discussed, and moreover, emphasis is placed on four controversial issues such as the use of prophylactic coronary revascularization in patients with myocardial ischemia, the perioperative management of patients with congestive heart failure, the routine use of betablockers and statins, and, finally, the management of antiplatelet therapies in patients with coronary stents. In addition to promoting an improvement of immediate perioperative care, the preoperative cardiological evaluation should be a challenge for identifying subjects with enhanced risk of cardiovascular events, who should be treated and monitored during a long-term follow-up.

Background: The early period following the onset of acute coronary syndromes (ACS) represents a critical stage of coronary heart disease with a high risk for recurrent events and deaths. The short-term effects of early treatment with statins in patients suffering from ACS on patient-relevant outcomes are unclear., Objectives: To assess the benefits and harms of early administered statins in patients with ACS from randomized controlled trials (RCTs)., Search Strategy: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL (to 1 February 2010). No language restrictions were applied. We supplemented the search by contacting experts in the field, by reviewing reference lists of reviews and editorials on the topic, and by searching trial registries., Selection Criteria: RCTs comparing statins with placebo or usual care, initiation of statin therapy within 14 days following the onset of ACS, and follow-up of at least 30 days reporting at least one clinical outcome., Data Collection and Analysis: Two authors independently assessed study quality and extracted data. We pooled treatment effects and calculated risk ratios (RRs) for all outcomes in the treatment and control groups using a random effects model., Main Results: Eighteen studies (14,303 patients) compared early statin treatment versus placebo or usual care in patients with ACS. Compared to placebo or usual care, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction (MI), and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) and four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month and at four months, although there were favorable trends related to statin use for each of these endpoints. The incidence of episodes of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels > 10 times the upper limit of normal) in statin treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg., Authors' Conclusions: Based on available evidence, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS.

Aims: This study tested the hypothesis that the addition of full-dose atorvastatin (80 mg/day) to conventional medical treatment could reduce ischaemic recurrences after non-ST-elevation acute myocardial infarction (NSTE-AMI) in patients with severe and diffuse coronary artery disease (CAD) not amenable to any form of mechanical revascularisation., Methods and Results: The study was an open-label, randomised, controlled, blinded end-point classification trial, employing the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design. A total of 290 patients (mean age 74.6 +/- 9.6 years) with NSTE-AMI and angiographic evidence of severe and diffuse CAD, not amenable to revascularisation by either coronary surgery or angioplasty, were randomised to atorvastatin 80 mg/day (n = 144) or conventional medical treatment (n = 146). A primary end point event (combination of cardiovascular death, non-fatal acute myocardial reinfarction and disabling stroke within 12 months of randomisation) occurred in 16.0% of patients treated with atorvastatin 80 mg/day and in 26.7% of patients receiving conventional treatment (HR 0.56; 95% CI 0.33-0.93, p = 0.027). The study was not blinded. Consequently, a bias in the assessment of clinical outcome cannot be completely excluded., Conclusions: In conclusion, when compared with a conventional treatment strategy, full-dose therapy with atorvastatin 80 mg/day provides greater protection against ischaemic recurrences after NSTE-AMI in patients with severe, diffuse, non-revascularisable CAD.

Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers.

The aim of this study was to assess the impact of cardiac autonomic derangement on gender-associated functional outcome of patients with subacute ischemic stroke undergoing a hospital-based rehabilitation program. The study population included 126 consecutive first-ever stroke survivors (mean age 59.7 +/- 11.6 years). Time-domain measures of heart rate variability (HRV) by 24-hour Holter monitoring (HM) were considered in all cases. By the end of the rehabilitation program an unfavorable functional outcome with dependency (Barthel Index score of <75) was found in 27 men (40.3%) and in 31 women (52.5%; p = 0.168). Multivariate analysis demonstrated that high age, low Barthel Index score and low Rankin Scale score on admission were independent predictors of an unfavorable functional outcome in both men and women. The standard deviation of normal-to-normal RR intervals on HM was an independent predictor of rehabilitation outcome only in men (OR 15.29, 95% CI 2.47-46.58, p = 0.001). The presence of insular damage on neuroimaging studies was independently associated with an unfavorable functional outcome only in female (OR 18.89, 95% CI 2.34-71.4, p = 0.006). HRV does not predict functional outcome after rehabilitation in women. Instead, insular damage appears to have a role in determining the final results of rehabilitation in women but not in men., ((c) 2010 S. Karger AG, Basel.)

Unlabelled: The prevention of symptomatic heart failure represents the treatment of patients in the A and B stages of AHA/ACC heart failure classification. Stage A refers to patients without structural heart disease but at risk to develop chronic heart failure. The major risk factors in stage A are hypertension, diabetes, atherosclerosis, family history of coronary artery disease and history of cardiotoxic drug use. In this stage, blockers hypertension is the primary area in which beta blockers may be useful. Beta blockers seem not to be superior to other medication in reducing the development of heart failure due to hypertension. Stage B heart failure refers to structural heart disease but without symptoms of heart failure. This includes patients with asymptomatic valvular disease, asymptomatic left ventricular (LV) dysfunction, previous myocardial infarction with or without LV dysfunction. In asymptomatic valvular disease no data are available on the efficacy of beta blockers to prevent heart failure. In asymptomatic LV dysfunction only few asymptomatic patients have been enrolled in the trials which tested beta blockers. NYHA I patients were barely 228 in the MDC, MERIT and ANZ trials altogether. The REVERT trial was the only trial focusing on NYHA I patients with LV ejection fraction less than 40%. Metoprolol extended release on top of ACE inhibitors ameliorated LV systolic volume and ejection fraction. A post hoc analysis of the SOLVD Prevention trial demonstrated that beta blockers reduced death and development of heart failure. Similar results were reported in post MI patients in a post hoc analysis of the SAVE trial (Asymptomatic LV failure post myocardial infarction). In the CAPRICORN trial about 65% of the patients were not taking diuretics and then could be considered asymptomatic. The study revealed a reduction in mortality and a non-significant trend toward reduction of death and hospital admission for heart failure., Conclusions: beta blockers are not specifically indicated in stage A heart failure. On the contrary, in most of the stage B patients, and particularly after MI, beta blockers are indicated to reduce mortality and, probably, also the progression toward symptomatic heart failure.

Objective: Although decreased heart rate variability (HRV) has been well-documented in association with depression after myocardial infarction, this phenomenon has not been studied in patients with stroke. The present study was designed to prospectively assess heart rate in relationship to depression among patients with acute stroke., Design: Using 24-hour Holter monitoring, HRV was assessed., Setting: A large university rehabilitation hospital., Participants: Patients with first ever stroke and no other severe physical illness, cigarette smoking, or drug therapy that could affect HRV were evaluated over 24 hours for HRV., Measurements: Patients were evaluated using the Structured Clinical Interview for depression diagnosis. Severity was assessed by the Hamilton Depression Rating Scale. Stroke severity was assessed by the National Institutes of Health Stroke Scale, the Barthel Index, and the Mini- Mental State Exam. The standard deviation (SD) of time in milliseconds of normal to normal beats (SDNN) was the primary measure of HRV., Results: Among patients with poststroke major or minor depression (N = 33), the SDNN was 109 +/- 32.6 SD compared with nondepressed patients (N = 16) whose SDNN was 133.9 +/- 40.1 SD (Wilcoxon rank test S = 492, p = 0.048). The SDNN was significantly and independently related to the existence of depression, but no other intergroup differences., Conclusions: These findings, for the first time, have provided some evidence that both major and minor poststroke depression may lead to decreased HRV. Future research in larger groups of patients should determine whether other measures of HRV more specific to sympathetic-parasympathetic tone are decreased in patients with poststroke depression.

Background: We assessed the role of left ventricular ejection fraction and of ambulatory blood pressure monitoring (ABPM) to predict cardiac death and heart failure in patients with defibrillator fulfilling MADIT II criteria. ABPM variables assessed included: mean 24 hours diastolic and systolic blood pressure, mean 24 hours heart rate, and pulse pressure., Methods: We studied 105 consecutive patients (age 67 +/- 11), all with a defibrillator and ejection fraction or= 220 n = 71) had clinical events at 12-month follow-up, compared with 61% of patients with low PI (< 220 n = 34) (P < 0.0001)., Conclusion: The PI built by mean 24 hours diastolic and systolic blood pressure and age could be a simple method to stratify risk of cardiac death and acute heart failure in MADIT II patients, in whom ejection fraction, uniformly depressed, is not predictive.

Objectives: This investigation was undertaken to compare diabetic and non-diabetic hypertensive patients with a first acute non-ST segment elevation myocardial infarction (NSTEMI) and to assess the impact of clinical and laboratory parameters on the occurrence of in-hospital complications., Methods: The study population comprised 112 consecutive male hypertensive patients with their first NSTEMI, who were divided into two groups according to the presence of type 2 diabetes mellitus. All patients underwent echocardiography and 24-h electrocardiographic (ECG) and blood pressure monitoring within 48 h from admission., Results: Diabetic hypertensive patients had significantly higher mean daytime, night-time, 24-h systolic blood pressure and heart rate and hypertensive peaks (P < 0.01), more episodes of asymptomatic ST segment depression (P < 0.05), which were also more severe and prolonged (P < 0.01), and more episodes of non-sustained ventricular tachycardia (P = 0.01). Diabetic patients showed a greater left ventricular mass index (LVMI) and a lower left ventricular ejection fraction (LVEF) (P < 0.01). In-hospital adverse clinical events were more frequent in diabetic hypertensives compared to non-diabetics (40.3% versus 18.1%, P = 0.01). In particular, heart failure occurred during hospitalization in 33.3% versus 14.5% (P = 0.02). The difference in transient cerebral ischaemic attacks did not reach statistical significance (7.0% versus 1.8%, P = 0.18). Multivariate Cox proportional hazards analysis showed that the only independent predictors for the occurrence of in-hospital adverse clinical events in diabetic patients were: 24-h systolic blood pressure variability [relative risk (RR) = 1.013, 95% confidence interval (CI) = 1.001-1.025, P = 0.03]; mean 24-h heart rate (RR = 7.05, 95% CI = 1.35-35.9, P = 0.02) and the LVMI (RR = 1.9, 95% CI = 1.121-3.785, P = 0.02)., Conclusions: This study indicates that in-hospital complications, including heart failure and transient cerebral ischaemia, occur frequently during the acute phase of a first NSTEMI in patients with both diabetes and hypertension. The coexistence of diabetes and hypertension doubles the risk of complications with respect to hypertension alone. In addition, adverse events may appear despite an initial uncomplicated clinical presentation, which can be predicted by the early assessment of heart rate and blood pressure behaviour and by the echocardiographic assessment of left ventricular mass.

Background and Purpose: The majority of patients with previous ischemic stroke are expected to benefit significantly from long-term statin therapy. However, discontinuation of medication therapy frequently occurs in clinical practice. The aim of this study was to assess the impact of discontinued statin therapy on clinical outcome in patients discharged after an acute ischemic stroke., Methods: The study population included 631 consecutive stroke survivors (322 men and 309 women; mean+/-SD age, 70.2+/-7.6 years) without clinical evidence of coronary heart disease. All patients were discharged on statin therapy and were followed up for 12 months after the acute ischemic stroke., Results: Within 12 months from discharge, 246 patients (38.9%) discontinued statin therapy; the mean time from discharge to statin discontinuation was 48.6+/-54.9 days (median time, 30 days; interquartile range, 18 to 55 days). During follow-up, 116 patients died (1-year probability of death=0.18; 95% CI, 0.15 to 0.21). Multivariate analysis demonstrated that after adjustment for all confounders and interactions, statin therapy discontinuation (hazard ratio=2.78; 95% CI, 1.96 to 3.72; P=0.003) was an independent predictor of all-cause 1-year mortality., Conclusions: A large number of patients discontinue their use of statins early after acute stroke. Moreover, patients discontinuing statins have a significantly increased mortality during the first year after the acute cerebrovascular event. These findings suggest that patient care should be improved during the transition from a hospital setting to outpatient primary care.

Objectives: The aim of our study was to assess the possible role of a prognostic index based on ambulatory blood pressure monitoring in a large cohort of patients with recent myocardial infarction., Methods: The study population included 1335 consecutive patients admitted for ST elevation myocardial infarction and discharged alive from 48 Italian hospitals participating in the multicentric IMPRESSIVE (Infarto Miocardico, Pressione arteriosa e frequenza cardiaca. Studio Italiano di Valutazione Epidemiologica) study. Ambulatory blood pressure monitoring was performed 3 weeks after discharge, with a clinical follow-up of 12 months. End-points included cardiac death and new admission for heart failure. A prognostic index was obtained from the ambulatory blood pressure monitoring variables according to the formula: (220-age)-mean 24 h heart rate (m24hHR)+mean 24 h diastolic blood pressure (m24hDBP)., Results: Among many potential predictors only left-ventricular ejection fraction, creatinine levels, Killip class and the prognostic index were independently associated with events during the follow-up. In particular, higher values of the prognostic index were associated with a lower incidence of events, with an odds ratio of 0.958 (95% confidence intervals 0.943-0.974) and a 4% reduction in risk for each point of the prognostic index. Overall incidence of cardiac events was 6-fold higher in patients within the lowest quartile of the prognostic index (< or =148) compared with the other three quartiles (12 vs. 2, 1.4 and 2% respectively in the other three quartiles; P<0.0001)., Conclusions: A simple prognostic index based on ambulatory blood pressure monitoring and age may be a useful tool in predicting cardiac death and heart failure in patients with recent myocardial infarction.

Aim of This Study: To describe the extent to which hyperglycemia, hypertension, and dyslipidemia are currently detected, treated, and controlled in diabetic patients attending a network of urban community-based diabetic care clinics in Italy., Methods: The study population included 1078 consecutive patients with type 2 diabetes mellitus (47% women, mean age 67.6+/-9.8 years) visited at eight diabetic care clinics between 1 and 30 of November 2004. Values of glycosilated hemoglobin, blood pressure, and cholesterol subfractions, as well as clinical and medication data, were prospectively collected in all cases in a computerized database., Results: Despite a high prevalence of hypertension (66.6%), only 29.6% of patients met the treatment goal of a systolic blood pressure <130 mmHg, while a diastolic blood pressure <80 mmHg was reached by 38.6% of the study cohort. Optimal LDL cholesterol values (<100mg/dl) were present in just 25.5% of cases. Values of glycosilated hemoglobin <7% were present in 57.8% of patients., Conclusions: We conclude that adherence to current guidelines for cardiovascular prevention and cardiovascular risk factor control represent an exception in diabetic patients attending community-based diabetic care clinics. Major efforts are required to improve the quality of health care currently delivered to diabetic patients.

Objectives: The aim of this study was to compare--in patients with persistent and permanent atrial fibrillation (AF)--the efficacy and safety of left atrial ablation with that of a biatrial approach., Background: Left atrium-based catheter ablation of AF, although very effective in the paroxysmal form of the arrhythmia, has an insufficient efficacy in patients with persistent and permanent AF., Methods: Eighty highly symptomatic patients (age, 58.6 +/- 8.9 years) with persistent (n = 43) and permanent AF (n = 37), refractory to antiarrhythmic drugs, were randomized to two different ablation approaches guided by electroanatomical mapping. A procedure including circumferential pulmonary vein, mitral isthmus, and cavotricuspid isthmus ablation was performed in 41 cases (left atrial ablation group). In the remaining 39 patients (biatrial ablation group), the aforementioned approach was integrated by the following lesions in the right atrium: intercaval posterior line, intercaval septal line, and electrical disconnection of the superior vena cava., Results: During follow-up (mean duration 14 +/- 5 months), AF recurred in 39% of patients in the left atrial ablation group and in 15% of patients in the biatrial ablation group (p = 0.022). Multivariable Cox regression analysis showed that ablation technique was an independent predictor of AF recurrence during follow-up., Conclusions: In patients with persistent and permanent AF, circumferential pulmonary vein ablation, combined with linear lesions in the right atrium, is feasible, safe, and has a significantly higher success rate than left atrial and cavotricuspid ablation alone.

Context: The short-term effects of early treatment with statins in patients after the onset of acute coronary syndromes (ACS) for the outcomes of death, myocardial infarction (MI), and stroke are unclear., Objective: To evaluate relevant outcomes of patients from randomized controlled trials comparing early statin therapy with placebo or usual care at 1 and 4 months following ACS., Data Sources and Study Selection: Systematic search of electronic databases (MEDLINE, EMBASE, PASCAL, Cochrane Central Register) from their inception to August 2005, which was supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of randomized controlled trials that compared treatment with statins with a control, were initiated within 14 days after onset of ACS, and had a minimal follow-up of 30 days. Trials with cerivastatin were only included in a sensitivity analysis., Data Extraction: Information on baseline characteristics of included trials and patients, reported methodological quality, lipid levels, and clinical outcome was independently extracted by 2 investigators. Investigators from each included trial contributed additional data if necessary., Data Synthesis: Twelve trials involving 13 024 patients with ACS were included in the meta-analysis. The risk ratios for the combined end point of death, MI, and stroke for patients treated with early statin therapy compared with control therapy were 0.93 (95% confidence interval [CI], 0.80-1.09; P = .39) at 1 month and 0.93 (95% CI, 0.81-1.07; P = .30) at 4 months following ACS. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, fatal or nonfatal MI, or revascularization procedures (percutaneous coronary intervention or coronary artery bypass graft surgery). Sensitivity analyses with restriction to trials of high quality or with additional data from a large trial using cerivastatin indicated summary risk ratios even closer to 1., Conclusion: Based on available evidence, initiation of statin therapy within 14 days following onset of ACS does not reduce death, MI, or stroke up to 4 months.

Despite the wide improvement of diagnostic techniques and the introduction of effective pharmacological and instrumental therapeutic strategies aimed to the treatment of cardiovascular diseases, their incidence and lethality are still elevated, with economic implications increasingly less sustainable by the public medical systems. The modern practice of cardiovascular prevention requires, thus, that diagnostic and therapeutic interventions, both at population level and on the single patient, should be more and more precise, effective, and appropriate. From this point of view, a correct global cardiovascular risk stratification assumes a preponderant relevance, in order to allow an adequate therapeutical response. For this purpose several work instruments, as risk charts and guidelines, namely dedicated to arterial hypertension and dyslipidemias, were developed and offered to clinicians interested in cardiovascular prevention. The aim of this review is to illustrate, in synthesis, those instruments, aiming to facilitate their implementation, thus reducing the actual gap between theoretical indications and the real world.

Background: Recent studies have shown that autologous bone marrow mononuclear cell (aBM-MNC) transplantation can be effectively performed in human beings either by the coronary route or by endoventricular injections. However, scanty data are available for patients undergoing coronary artery bypass grafting (CABG). Accordingly, the aim of this study was to evaluate the feasibility and safety of aBM-MNC transplantation in patients with recent myocardial infarction undergoing CABG., Methods and Results: The study population included 36 consecutive patients with recent myocardial infarction (< 6 months) undergoing CABG. Eighteen patients (17 men, mean age 64 years) underwent CABG plus aBM-MNC transplantation, whereas 18 subjects undergoing conventional CABG (17 men, mean age 67 years) served as control subjects. Cell transplantation was performed by direct injections in the border zone of the recently infarcted area. An average number of 292 +/- 232 x 10(6) aBM-MNCs was injected in each patient. When compared with control subjects, transplanted patients showed higher values of troponin I peak after CABG (median values of 1.65 ng/mL vs 0.64 ng/mL, P < .001). No major transplant-related adverse event could be detected. During follow-up, transplanted patients had an improvement in left ventricular ejection fraction (from 0.46 to 0.51, P < .05) and wall motion score index (from 1.71 to 1.42, P < .01). The incidence of arrhythmias immediately after CABG and during follow-up was similar in the 2 groups., Conclusions: Our data support the idea that direct injection of aBM-MNCs in the myocardium during CABG is feasible and safe. Larger studies are needed to assess the efficacy of such an approach in patients undergoing CABG.

A metastatic involvement of the heart is an uncommon phenomenon in clinical practice; it is more frequent in patients with end-stage disease and a wide tumor spread. The clinical diagnosis is very difficult because there are no early symptoms and most often, the presence of metastases in other sites, such as lung and lymph nodes, may determine a misunderstanding of the clinical picture. We report the case of a young male (44 years old) with a complete atrioventricular block due to metastatic myocardial involvement from a primary occult lung cancer. The first symptom of the disease was a syncopal spell. In spite of permanent pacemaker implantation, the patient died suddenly and unexpectedly after 3 days. Autopsy revealed an anaplastic carcinoma of the right lung hilus. The myocardium was invaded by numerous metastatic nodules, particularly in the interventricular septum and in the left ventricular wall.

Background and Purpose: Acute stroke is associated with impairment of cardiac autonomic balance and increased incidence of arrhythmias. These abnormalities appear more relevant in the case of involvement of the right insula in the infarct area. The aim of this study was to assess the impact of right-sided insular damage, cardiac autonomic derangement, and arrhythmias on clinical outcome after acute ischemic stroke., Methods: Holter monitoring for 24 hours was performed in 208 consecutive patients with first-ever acute ischemic stroke. Time- and frequency-domain measures of heart rate variability and arrhythmias were considered in all cases. All patients were followed for a 12-month period after the initial event., Results: During the 12-month follow-up period, 48 patients died (1-year probability of death, 0.23; 95% CI, 0.17 to 0.30). Multivariate analysis demonstrated that age (hazard ratio [HR], 1.06; 95% CI, 1.01 to 1.10; P=0.0087), stroke severity on admission (HR, 1.25; 95% CI, 1.13 to 1.39; P=0.0001), presence of right-sided insular damage (HR, 2.01; 95% CI, 1.13 to 1.39; P=0.0187), as well as lower values of the SD of all normal-to-normal RR intervals (HR, 3.32; 95% CI, 1.67 to 6.24; P=0.002), and presence of nonsustained ventricular tachycardia during Holter monitoring (HR, 2.99; 95% CI, 1.58 to 5.67; P=0.0007) were independent predictors of 1-year mortality., Conclusions: The integration of traditional risk stratifiers with autonomic and arrhythmic markers, and the careful search for right-sided insular involvement, may represent an effective approach for identification of stroke patients at risk for early mortality.

Objectives: The aim of this study was to assess the efficacy of preoperative and postoperative treatment with n-3 polyunsaturated fatty acids (PUFAs) in preventing the occurrence of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG)., Background: Postoperative AF is a common complication of CABG. There is growing clinical evidence that PUFAs have cardiac antiarrhythmic effects., Methods: A total of 160 patients were prospectively randomized to a control group (81 patients, 13 female, 64.9 +/- 9.1 years) or PUFAs 2 g/day (79 patients, 11 female, 66.2 +/- 8.0 years) for at least 5 days before elective CABG and until the day of discharge from the hospital. The primary end point was the development of AF in the postoperative period. The secondary end point was the hospital length of stay after surgery. All end points were independently adjudicated by two cardiologists blinded to treatment assignment., Results: The clinical and surgical characteristics of the patients in the two groups were similar. Postoperative AF developed in 27 patients of the control group (33.3%) and in 12 patients of the PUFA group (15.2%) (p = 0.013). There was no significant difference in the incidence of nonfatal postoperative complications, and postoperative mortality was similar in the PUFA-treated patients (1.3%) versus controls (2.5%). After CABG, the PUFA patients were hospitalized for significantly fewer days than controls (7.3 +/- 2.1 days vs. 8.2 +/- 2.6 days, p = 0.017)., Conclusions: This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF (54.4%) and was associated with a shorter hospital stay.

Clinical studies suggest that stem cell transplantation (SCT) is feasible and has the potential for beneficial effects in several cardiac affections, including myocardial infarction and advanced heart failure. However, concern exists about the possible occurrence of serious arrhythmias after SCT, even if such complication has been shown only in case of skeletal myoblast transplantation. SCT might induce arrhythmias by several mechanisms, such as electrotonic stimulation of cardiac cells, electrical heterogeneity of action potentials during stem cell differentiation process, increased nerve sprouting, and local tissue injury induced by intramyocardial injection. As a matter of fact, the use of endothelial progenitor cells from the peripheral blood or of stem cells from bone marrow has not been associated with any significant cardiac rhythm disturbance. Recently, a new opportunity for SCT has emerged: the development of a biological cardiac pacemaker. Both gene therapy and cell therapy have been used in this new perspective. In fact, at present, the transformation of a normal cardiomyocyte in a pacemaker cell can be obtained in animal models by the injection of a plasmid or virus, incorporating the gene encoding for specific proteins. This procedure transforms cardiomyocytes in transgenic cells that may show an overexpression of beta2-adrenergic receptors, or abnormal membrane ion channels. As an alternative, genetically modified mesenchymal stem cells can be delivered within the heart and engraft to develop a biological pacemaker. To date, several studies have been performed in different animal models employing both cell and gene therapy. However, complex problems concerning safety and efficacy require a solution before we can move to the step of clinical evaluation in human beings.

Aims: This study was undertaken to evaluate the epidemiological features and the prognostic implications of syncope in young athletes., Methods and Results: A cohort of 7568 young athletes (5132 males, 2436 females, aged 16.2 +/- 2.4) underwent a pre-participation evaluation. A syncopal spell in the last 5 years was reported by 474 athletes (6.2%). Syncope was unrelated with exercise in 411 athletes (86.7%), post-exertional in 57 (12.0%) and exertional in 6 (1.3%). All episodes of non-exertional or post-exertional syncope had the typical features of neurally-mediated fainting. The 6 athletes with exertional syncope underwent further testing allowing the diagnosis of hypertrophic cardiomyopathy in one case, and of right ventricular outflow tract tachycardia in another. The remaining 4 athletes only showed a positive response to tilt-testing. All athletes were followed for 6.4 +/- 3.1 years, during 48,066.6 person-years of follow-up. The recurrence rate was 20.3 per 1000 subject-years in athletes with non-exertional, and 19.2 per 1000 subject-years in athletes with post-exertional syncope. The incidence of first report of syncope was 2.2 per 1000 subject-years for non-exertional and 0.26 per 1000 subjects-years for post-exertional spells. No other adverse event was noted during follow-up., Conclusions: In young athletes, syncope occurring before the initial pre-participation screening has a neurally-mediated origin in most cases and shows a low recurrence rate. Exercise-related syncope is infrequent and is not associated with an adverse outcome in subjects without cardiovascular abnormalities. The incidence of new syncope during competitive activity is particularly low.

Objectives: The purpose of this research was to evaluate the impact of athletic training and, in particular, physical deconditioning, on frequent and/or complex ventricular tachyarrhythmias assessed by 24-h ambulatory (Holter) electrocardiogram (ECG)., Background: Sudden deaths in athletes are usually mediated by ventricular tachyarrhythmias., Methods: Twenty-four hour ambulatory ECGs were recorded at peak training and after a deconditioning period of 19 +/- 6 weeks (range, 12 to 24 weeks) in a population of 70 trained athletes selected on the basis of frequent and/or complex ventricular tachyarrhythmias (i.e., > or =2,000 premature ventricular depolarization [PVD] and/or > or =1 burst of non-sustained ventricular tachycardia [NSVT]/24 h)., Results: A significant decrease in the frequency and complexity of ventricular arrhythmias was evident after deconditioning: PVDs/24 h: 10,611 +/- 10,078 to 2,165 +/- 4,877 (80% reduction; p < 0.001) and NSVT/24 h: 6 +/- 22 to 0.5 +/- 2, (90% reduction; p = 0.04). In 50 of the 70 athletes (71%), ventricular arrhythmias decreased substantially after detraining (to <500 PVDs/24 h and no NSVT). Most of these athletes with reduced arrhythmias did not have structural cardiovascular abnormalities (37 of 50; 74%). Over the 8 +/- 4-year follow-up period, each of the 70 athletes survived without cardiac symptoms., Conclusions: Frequent and/or complex ventricular tachyarrhythmias in trained athletes (with and without cardiovascular abnormalities) are sensitive to brief periods of deconditioning. In athletes with heart disease, the resolution of such arrhythmias with detraining may represent a mechanism by which risk for sudden death is reduced. Conversely, in athletes without cardiovascular abnormalities, reduction in frequency of ventricular tachyarrhythmias and the absence of cardiac events in the follow-up support the benign clinical nature of these rhythm disturbances as another expression of athlete's heart.

Background and Purpose: The insula of the right cerebral hemisphere may have a major role in cardiac autonomic control. This study was aimed at assessing the effects of acute right insular ischemic damage on heart rate variability (HRV) and arrhythmias., Methods: Holter monitoring for 24 hours was performed in 103 consecutive patients with first-ever acute ischemic stroke. Time and frequency domain measures of HRV and arrhythmias were considered in all cases., Results: Forty-nine patients (47.5%) had a right-sided infarction, whereas 54 (52.5%) had a left-sided infarction. Insular involvement was present in 33 patients with right-sided stroke (67.3%) and in 36 patients with left-sided stroke (66.6%). When compared with all other stroke patients, subjects with right-sided insular damage showed significantly lower values of the standard deviation of all normal-to-normal (SDNN) R wave to R wave (RR) intervals and of the root mean square of differences (rMSSD) of adjacent normal-to-normal RR intervals, and higher low-frequency/high-frequency ratio values (P<0.05). Right insular stroke was also associated with more complex arrhythmias than any other localization (P<0.05). Moreover, in the whole population of stroke patients, lower values of SDNN were associated with the presence of more frequent and complex arrhythmias., Conclusions: These findings further support the notion that the right insula is implicated in the autonomic control of cardiac activity and that acute right insular damage may lead to a derangement of cardiac function with potential prognostic implications.

Aims: Aim of the present study was the development and the subsequent validation of a simple risk classification system for patients presenting with syncope to the emergency departments., Methods and Results: A group of 270 consecutive patients (145 females, mean age 59.5 years) presenting with syncope to the emergency departments of six community hospitals of the Lazio region of Italy was used as a derivation cohort for the development of the risk classification system. Data from the baseline clinical history, physical examination and electrocardiogram were used to identify independent predictors of total mortality within the first 12 months after the initial evaluation. Multivariate analysis allowed the recognition of the following predictors of mortality: (1) age >65 years; (2) cardiovascular disease in clinical history; (3) syncope without prodromes; and (4) abnormal electrocardiogram. The OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) score was calculated by the simple arithmetic sum of the number of predictors present in every single patient. Mortality increased significantly as the score increased in the derivation cohort (0% for a score of 0, 0.8% for 1 point; 19.6% for 2 points; 34.7% for 3 points; 57.1% for 4 points; p<0,0001 for trend). A similar pattern of increasing mortality with increasing score was prospectively confirmed in a second validation cohort of 328 consecutive patients (178 females; mean age, 57.5 years)., Conclusions: Clinical and electrocardiographic data available at presentation to the emergency department can be used for the risk stratification of patients with syncope. The OESIL risk score may represent a simple prognostication tool that could be usefully employed for the triage and management of patients with syncope in emergency departments.

Background: A better understanding of transseptal activation may be important for the treatment of atrial fibrillation, but little is known about preferential routes of conduction from the left atrium (LA) to the right atrium (RA) in humans., Methods and Results: Twelve patients were studied. A noncontact mapping system was used to map the RA during pacing from several sites of LA at different cycle lengths. The location of the Bachmann's bundle (BB), the fossa ovalis (FO) and the coronary sinus (CS) ostium were determined using intracardiac echocardiography. The BB was the earliest area of right atrial activation during pacing from the atrial appendage, roof and postero-superior wall in 94% of cases. The FO was the area of earliest activation during pacing from the septum and the right superior pulmonary veins (PV) in 95% of cases. The CS ostium (alone or associated with the FO) was the region of transseptal breakthrough in all patients during pacing from the right inferior PV, postero-inferior wall and distal CS. Various patterns of activation with 2 or 3 distinct areas of transseptal breakthrough were observed during pacing from the lateral wall and the left superior PV. The pacing cycle length did not influence the modality of transseptal activation., Conclusions: Different patterns of transseptal activation were found during pacing from LA. The preferential routes of conduction from the LA to the RA were related to the sites of stimulation and were not influenced by the pacing cycle length.