Effect of Postablation Statin Treatment on Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Statins have been proposed as a means to prevent postablation atrial fibrillation (AF) recurrences, mainly on the basis of their pleiotropic effects. The objective of this subanalysis of a prospectively randomized controlled study population of patients undergoing radiofrequency ablation for paroxysmal AF was to test the hypothesis that statin treatment is associated with longer time to recurrence. METHODS AND RESULTS: This is a subanalysis over an extended follow-up period of a prospective randomized study (ClinicalTrials.gov Identifier NCT01791699). Among 291 patients, 2 propensity score-matched subgroups of patients who received or did not receive statins after pulmonary vein isolation were created. In the unmatched cohort, there was no difference in the rate of recurrence between statin-treated and not treated patients, with a 1-year recurrence estimate of 19% and 23%, respectively (Gehan statistic 0.59, P = 0.443). In the propensity-matched cohort (N = 166, 83 per group), recurrence-free survival did not differ significantly between groups (839 days, 95% confidence interval 755-922 days, in the no statin group vs. 904 days, 95% confidence interval 826-983 in the statin group; P = 0.301). The 1-year recurrence rate estimate was 30% in the no statin group versus 27% in the statin group (Gehan statistic 0.56, P = 0.455). CONCLUSION: Statin treatment does not seem to affect AF recurrence in following radiofrequency ablation for paroxysmal AF, over a follow-up time of about 2.5 years.

Colchicine Pharmacokinetics and Mechanism of Action.

Colchicine is a tricyclic, lipid-soluble alkaloid derived from the plant of the Lily family Colchicum autumnale, sometimes called the "autumn crocus". It is predominantly metabolized in the gastrointestinal tract. Two proteins, P-glycoprotein (P-gp) and CYP3A4 seem to play a pivotal role, governing its pharmacokinetic. The commonest side effects are gastrointestinal (nausea, vomiting and particularly dose-related-diarrhea) occurring in 5-10% of patients. Colchicine exerts its unique action mainly through inhibition of microtubule polymerization. Microtubule polymerization affects a variety of cellular processes including maintenance of shape, signaling, division, migration, and cellular transport. Colchicine interferes with several inflammatory pathways including adhesion and recruitment of neutrophils, superoxide production, inflammasome activation, the RhoA/Rho effector kinase (ROCK) pathway and the tumor necrosis factor alpha (TNF-α) -induced nuclear factor κΒ (NF-κΒ) pathway attenuating the inflammatory response. This concise paper attempts to give a brief review of its pharmacokinetic properties and its main mechanisms of action.

The role of the immunogenetic background in the development and recurrence of acute idiopathic pericarditis.

OBJECTIVES: We assessed the role of the immunogenetic background in the development and recurrence of acute idiopathic pericarditis (AIP). METHODS: Fifty-five patients with a first episode of AIP were followed for 23.8 ± 6.3 months and recurrences were recorded. The control group consisted of 246 healthy individuals. In all subjects, genomic human leukocyte antigen (HLA) typing was performed. Moreover, circulating lymphocyte subpopulations were studied in 44 randomly selected patients and in 20 controls. RESULTS: An increased frequency of HLA-A*02, -Cw*07 and -DQB1*0202 alleles, and a decreased frequency of the -DQB1*0302 allele was detected in patients with AIP. The recurrence rate was 40% and time to recurrence was 202.8 ± 164.1 days. In patients with idiopathic recurrent pericarditis (RP), increased frequencies of HLA-A*02, -Cw*07 and -DQB1*0202 alleles were found. Notably, no patient with RP exhibited HLA-DRB1*04 and -DQB1*0302 alleles. Patients with RP exhibited lower CD4+/CD45RA+ naïve T cells (p = 0.03) than controls, and higher CD8+DR+ activated T cells (p = 0.01) than patients without recurrence and controls. CONCLUSIONS: HLA alleles may confer either susceptibility or resistance to AIP and RP. Circulating T-cell subpopulations may also predict RP. A combination of the above parameters might help to better define patients prone to recurrence.

Acute coronary occlusion following TAVI.

Transcatheter aortic valve implantation (TAVI) has nowadays replaced open heart surgery as an alternative therapeutic tool in selected patients. Thirty-five percent of patients with severe degenerative aortic valve stenosis (AS) remain untreated because of the existing comorbidities that increase their perioperative risk. TAVI is a relatively new technique that has "come to stay" in the everyday clinical practice considering, that is the only alternative to surgery and appears to have excellent long term results. Herein, we describe a vascular complication immediately after the implantation of the Edwards SAPIEN (Edwards Lifesciences, Irvine, CA) prosthesis, followed by ad hoc percutaneous coronary intervention.

Recurrent apical ballooning syndrome "The masquerading acute cardiac syndrome".

Left ventricle (LV) apical ballooning syndrome (ABS) is a recently established reversible cardiomyopathy (CM) that presents as acute coronary syndrome (ACS) with ST segment elevation and specific echocardiographic (Echo) findings in the absence of significant coronary artery disease. Synonyms of ABS include "stress-induced CM" and "Takotsubo CM", terms that describe primarily the pathophysiology and the Echo findings of the syndrome respectively. This syndrome is a rare entity, accounting for the 2.2% of the ST segment elevation ACS, while recurrence rates reach 10% four years after the initial episode [1]. Herein we describe the first case in the literature of an 83 year-old (yo), female patient who suffered two episodes of ABS, the first in 1999 when the syndrome was unknown and diagnosis was "ST segment elevation myocardial infraction (STEMI)'' and the other one eight years later in 2007.

Time rate of blood pressure variation is superior to central hemodynamics as an associate of carotid intima-media thickness.

OBJECTIVE: The extent of target organ damage has been associated with both central hemodynamics and arterial stiffening, and the time rate of blood pressure (BP) changes in essential hypertension. However, the relative significance of these parameters has not been examined. METHODS: We recruited 232 consecutive uncomplicated newly diagnosed hypertensive patients and 241 normotensive individuals. Twenty-four-hour ambulatory BP monitoring was performed in all individuals. The time rate of SBP variation was computed as the first derivative of the SBP values against time. Aortic central SBP and central DBP, central pulse pressure, central augmentation index and central augmentation pressure were assessed noninvasively by pulse wave analysis. Common carotid artery intima-media thickness was measured by high-resolution ultrasonography. RESULTS: Median 24-h time rate of BP changes was 0.571 +/- 0.114 mmHg/min. Traditional risk factors, office SBP, several ambulatory BP monitoring parameters (24-h SBP, 24-h pulse pressure, 24-h heart rate and BP dipping), 24-h time rate of BP changes, time rate of BP changes at different time intervals, and central SBP, central pulse pressure, central augmentation index and central augmentation pressure significantly correlated with intima-media thickness. Age, sex, BMI, 24-h time rate of BP changes, time rate of BP changes measured at 0100-0600 h and 24-h heart rate remained significant associates of intima-media thickness after adjustment for confounding factors. By multivariate stepwise linear regression, 24-h time rate of BP changes and time rate of BP changes at 0100-0600 h had incremental value over traditional risk factors, other ambulatory BP monitoring parameters and central hemodynamics. CONCLUSION: These findings indicate that time rate of BP variation is superior to central hemodynamics as an associate of carotid intima-media thickness in hypertensive and normotensive individuals.

Heartscore calculated in individuals younger than 40 years is related to vascular markers of early atherosclerosis.

BACKGROUND: Heartscore is not well validated for individuals less than 40 years of age. In the latest guidelines a relative risk chart is provided with the proposal to be used for young adults aged less than 60 years instead of projecting risk at the age of 60 years. Moreover, coronary artery disease is insidiously manifested in younger patients. DESIGN: Cross-sectional study. METHODS: Two hundred and two young Greeks of age less than 40 years and 232 middle-aged adults aged 40-60 years without clinically overt cardiovascular disease or diabetes were consecutively recruited. Flow-mediated dilatation of the brachial artery, carotid, and femoral intima media thickness (IMT), carotid-radial and carotid-femoral pulse wave velocity (PWV) were measured in all individuals in one session. The European Society of Cardiology online Heartscore calculator was used for mortality risk (MR) 60 and Systematic Coronary Risk Evaluation risk charts for relative risk (RR) computation. RESULTS: MR60 in the younger significantly correlated with all measured vascular markers whereas RR significantly correlated with carotid IMT. By multivariate regression analysis, MR60 was a stronger identifier than RR for PWV, mean carotid and femoral IMT in both groups. Young adults (<40 years) with a high MR60 (>5%) had significantly higher carotid-radial PWV, carotid and femoral IMT whereas those with a high RR (>3rd tertile) had significantly higher carotid IMT. CONCLUSION: MR60 was a stronger identifier of most of the measured markers of early atherosclerosis as compared with RR. These data support Heartscore as a prognostic tool in terms of primary prevention for participants younger than 40 years old.

Clinical value of B-type natriuretic peptide for the assessment of left ventricular filling pressures in patients with systolic heart failure and inconclusive tissue Doppler indexes.

Invasive hemodynamic monitoring with Swan-Ganz catheterization to guide treatment decisions in heart failure may be hazardous and may lack prognostic value. We assessed the clinical utility of B-type natriuretic peptide (BNP) in estimating left ventricular filling pressures in patients with inconclusive tissue Doppler indexes. In this study, 50 patients with systolic heart failure and an early transmitral velocity to early diastolic mitral annular velocity ratio (E/Ea) between 8 and 15 were studied. Among them, 25 had been admitted for acutely decompensated heart failure (group A) and the remainder were clinically stable outpatients (group B). All patients underwent simultaneous invasive pulmonary capillary wedge pressure (PCWP) determination, BNP measurement, and echocardiography. In group A, BNP correlated with PCWP (r = 0.803, P < 0.001), deceleration time (DT, r = -0.602, p = 0.001), and end-systolic wall stress (SWS, r = 0.565, P = 0.003). In multivariate analysis, BNP was the only parameter independently associated with PCWP (P = 0.023). In group B, no correlation was found between BNP and PCWP or SWS, while DT correlated significantly with both PCWP (r = -0.817, P < 0.001) and BNP (r = -0.8, P < 0.001). We conclude that BNP may be a useful noninvasive tool for the assessment of left ventricular filling pressures in patients with acutely decompensated heart failure and inconclusive tissue Doppler indexes.

A variant form of acute reversible cardiomyopathy: a case report.

INTRODUCTION: Stress cardiomyopathy, also known as Takotsubo cardiomyopathy or left ventricular apical ballooning, has been linked to emotional or physical stress resulting in transient left ventricular dysfunction. It typically affects the mid and apical left ventricular segments. At onset, it resembles acute myocardial infarction, due to the acute onset of chest pain and ST-T segment elevation. However, there is minimal biomarker elevation and a normal coronary artery angiogram. CASE PRESENTATION: We report a case of a woman with transient myocardial injury after a stressful event, presenting with a variation of the affected segments. In this case, only the basal and mid portions of the left ventricle were affected, while the apex was completely spared. Coronary angiography revealed no significant occlusion and left ventricular function had recovered completely by the third day of hospitalization. CONCLUSION: We present a variant form of stress cardiomyopathy, affecting the basal and mid segments of the left ventricle.

Serum levels of the osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, metalloproteinase-1 (MMP-1) and tissue inhibitors of MMP-1 levels are increased in men 6 months after acute myocardial infarction.

BACKGROUND: Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) are critical regulators of bone remodeling and RANKL/RANK signaling could also play an important role in the remodeling process of several tissues, such as myocardium. Therefore, we investigated whether the serum concentrations of OPG and RANKL correlate with the serum levels of metalloproteinase-1 (MMP-1), MMP-9 and tissue inhibitors of MMP-1 (TIMP-1), which are known regulators of myocardial healing in acute myocardial infarction (AMI) patients. METHODS: We analyzed blood samples from 51 consecutively hospitalized men with AMI, 12 men with established ischemic heart failure (New York Heart Association category II, NYHA-II) and 12 healthy men age-matched to the NYHA-II patients. Serum levels of MMP-1, MMP-9, TIMP-1, OPG and RANKL were quantified using commercially available ELISA kits. AMI patients were sampled 4 days and 6 months after MI. RESULTS: Our data revealed increased serum levels of OPG, RANKL, MMP-1 and TIMP-1 levels and significant correlations between increased RANKL levels and MMP-1 and TIMP-1 serum levels 6 months after MI. In addition, the ratio OPG/RANKL was very low 6 months after MI, suggesting that the nuclear factor kappa-B signaling is possibly more active 6 months post-MI than it is on day 4 post-MI. CONCLUSIONS: Our data suggest that OPG, RANKL, MMP-1 and TIMP-1 serum levels can be potential mediators of myocardial healing after MI. However, further large studies are needed to confirm the utility of OPG and RANKL as markers of healing after ST elevation in MI.

Functional electrical stimulation improves endothelial function and reduces peripheral immune responses in patients with chronic heart failure.

BACKGROUND: Previous studies have shown beneficial effects of functional electrical stimulation (FES) on muscle performance and exercise capacity of patients with chronic heart failure. This study evaluates the impact of FES on endothelial function and peripheral markers of immune activation in patients with moderate to severe heart failure. METHODS: Twenty-four patients with a left ventricular ejection fraction of less than 40% and New York Heart Association class II-III symptoms, undergoing optimized drug therapy, were randomly assigned (2 : 1) to a 6-week training programme of FES (n=16) or served as controls (n=8). Endothelial function was assessed by Doppler flow-mediated dilatation (FMD) of the brachial artery before and after the training programme. Peripheral pro-inflammatory/anti-inflammatory markers such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1 and IL-10 were also measured before and after training. RESULTS: A significant improvement on the 6-min walk test (7.5+/-3.3%), Minnesota Living Score (18.2+/-8.6%) and FMD (38.5+/-15.1%) was observed only in the FES-treated group. FES also causes a significant reduction of TNF-alpha (-11.5+/-8.9%), sICAM-1 (-13.1+/-9.8%), and sVCAM-1 (-10.6+/-6.6%), as well as a respective increase in the ratio IL-10/TNF-alpha (37.1+/-29.4%). In the FES group, the percentage improvement in the Minnesota Living Score was significantly correlated with respective changes in circulating TNF-alpha (r=0.624, P<0.01), sVCAM-1 (r=0.665, P<0.001) and the ratio IL-10/TNF-alpha (r=-0.641, P<0.01). CONCLUSION: FES is an exercise training programme that improves endothelial function in patients with chronic heart failure, and also has anti-inflammatory effects.

Effect of lipid levels and lipid-lowering therapy on restenosis after coronary artery stenting.

BACKGROUND: Recent experimental and clinical data suggest that lowering serum lipid levels with statins may prevent or delay the process of restenosis. The purpose of this trial is to determine whether lipid levels relate to restenosis and/or whether statin therapy can prevent or delay the process of restenosis after intracoronary stenting. METHODS: One hundred thirty-six patients who underwent single coronary artery stenting from June 1995 to June 1997 in our institution were included in the study. All these patients were followed for at least 9 months (mean 392+/-148 days) for major adverse cardiac events (MACE). We defined as MACE the occurrence of death, myocardial infarction, or need for target lesion revascularization. From this cohort, 103 patients had at least one lipid parameter from the lipid profile evaluated within 2 months from the date of the procedure. Patients who had the stent because of an acute myocardial infarction were included in the study only if their lipid profile was evaluated before or at least 6 weeks after the event. Patients with triglyceride levels above 500 had both triglyceride and low-density lipoprotein cholesterol levels excluded from the statistical analysis. Patients were divided into two groups based on lipid levels: normal (Group I; n=31) and elevated (Group II; n=72). Patient outcomes were also analyzed by statin therapy use. RESULTS: There was no significant difference in MACE rates between the two groups when outcomes were analyzed by lipid levels (22.6% versus 20.8% P=0.8). Furthermore, outcomes were analyzed by use of statin therapy (Group III, n=53, on statin versus Group IV, n=50, on no statin). There was also no difference in MACE rates between the two groups (20.8% versus 22%; P=0.8). CONCLUSION: The process of restenosis has unique features that differentiate it from atherosclerosis. Although lipid-lowering therapy is crucial in delaying the process of atherosclerosis, its role in the prevention of restenosis is yet to be proven.

Comparison of myocardial contrast echocardiography with SPECT in the evaluation of coronary artery disease in asymptomatic patients with LBBB.

OBJECTIVE: The non-invasive assessment of coronary artery disease (CAD) in patients with left bundle branch block (LBBB) is troublesome. In this study, we investigated the diagnostic accuracy of myocardial contrast echocardiography (MCE) with adenosine to detect CAD in asymptomatic patients with LBBB, and we compared it with single photon emission computed tomography (SPECT) with adenosine. METHODS: Forty-seven patients with LBBB, and no previously documented CAD, initially underwent SPECT imaging and 1-3 days later MCE. Coronary arteriography was performed within 1 week from the latter procedure. RESULTS: The overall sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and kappa index of concordance of SPECT were 73%, 72%, 44%, 90%, 72%, and 0.37+/-0.13, respectively, whereas those of MCE were 91%, 92%, 77%, 97%, 92%, and 0.77+/-0.1, respectively (p<0.05 for all comparisons). Significant CAD was present in 11 patients (23%). Left anterior descending coronary artery was involved in 8 patients, left circumflex artery in 2 patients, and right coronary artery in 4 patients. Concerning the left anterior descending artery disease detection, SPECT had a sensitivity of 75%, a specificity of 79%, a positive predictive value of 43%, a negative predictive value of 94%, and a diagnostic accuracy of 79%. The respective values of MCE were 100% for all of the above variables. CONCLUSIONS: MCE with adenosine has a higher global diagnostic accuracy compared to SPECT for the detection of CAD in patients with LBBB, mainly due to the poor specificity of SPECT concerning perfusion defects detection in the left anterior descending artery territory.