Flecainide: Current status and perspectives in arrhythmia management.

Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease.

Economic evaluation of dabigatran etexilate in the management of atrial fibrillation in Greece.

INTRODUCTION: The objective of the present study was to evaluate, from an economic perspective, dabigatran etexilate in comparison to existing pharmaceutical therapeutic options available for the protection of moderate-to-high risk patients with non-valvular atrial fibrillation from cardioembolic risk. METHODS: An existing Markov model was adapted to the Greek setting to reflect the natural course of the disease and the management of patients with different therapies. The model predicts health and economic outcomes and the implications for the social security system during the course of a patient's lifetime. The data for the population of the model were derived from the international literature and local economic databases. RESULTS: The incremental cost per quality-adjusted life year (QALY) of dabigatran 150 mg twice daily relative to the other therapies varied from €5547 to €11,762 and that of dabigatran 110 mg twice daily from €7398 to €16,437. The incremental cost per QALY of dabigatran 150 mg relative to aspirin, the least costly option, was €11,762 and relative to warfarin and acenocoumarol, the local standards of care, it was €11,400 and €11,224 respectively, well below the local thresholds of acceptance. CONCLUSION: Dabigatran etexilate may represent a cost-effective option for the prevention of thromboembolic events in AF patients at moderate-to-high risk of stroke or systemic embolism.

Correlation of mechanical dyssynchrony with QRS duration measured by signal-averaged electrocardiography.

BACKGROUND: Preimplantation left ventricular dyssynchrony is considered a prerequisite for a beneficial response to cardiac resynchronization therapy (CRT). However, electrical dyssynchrony estimated by QRS duration (QRSd) on ECG has not been proven to be an optimal surrogate of mechanical dyssynchrony. We evaluated the correlation of mechanical dyssynchrony with QRSd as measured by signal-averaged electrocardiography (SAECG) in comparison with measurements based on conventional surface ECG and with onscreen measurements based on digital ECG. METHODS: We included 49 consecutive patients with decompensated heart failure (40 men, aged 66.8 +/- 9.5 years), New York Heart Association (NYHA) class II-IV, and LVEF < or = 40%. QRSd was calculated by manual measurement of 12-lead ECG, on-screen measurement of computer-based ECG, and calculation of total ventricular activation time on SAECG. RESULTS: Only 60.4% of the studied patients had QRS > or = 120 ms based on measurements derived by SAECG compared to 69.4% by using on-screen measurement of computer-based ECG and 73.5% based on surface ECG (P=0.041). Interventricular but not intraventricular delay was correlated with QRSd. The correlation of interventricular dyssynchrony with QRSd was stronger when measured by SAECG than by surface ECG (r=0.45, P=0.001 vs r=0.35, P < 0.01). Among patients with ischemic cardiomyopathy, no significant correlation was demonstrated between mechanical dyssynchrony and QRSd. In nonischemic patients, interventricular delay was significantly correlated with QRSd measured by surface ECG (r=0.45, P < 0.05) and SAECG (r=0.46, P < 0.05). CONCLUSIONS: The use of SAECG results in different patient classification in wide QRS complex category as compared to surface ECG. Furthermore, QRSd measured by SAECG is correlated with interventricular but not intraventricular dyssynchrony in heart failure patients.

Duration of treadmill exercise testing combined with QRS score predicts adverse cardiac outcome at long-term follow-up.

OBJECTIVE: Total exercise duration and abnormal QRS score values are treadmill exercise testing (TET) prognostic parameters that have been shown to be significantly and independently associated with cardiac mortality. We evaluated the prognostic value of a new index (M score, Michaelides score) incorporating TET duration and QRS score values in a simple index. METHODS: In this study, we included 626 patients, who underwent TET and coronary arteriography. Cardiac catheterization showed the presence of coronary artery disease in 64.3% of these patients. The M score was calculated by adding the value of the Athens QRS score to the duration of TET (in minutes). The outcome measure was a composite of myocardial infarction or death. Patients were prospectively followed for 38+/-21 months (median 36 months). RESULTS: The composite endpoint was more frequent among the patients of the 1st quartile (M-score values <-5.8). In univariate analysis, mortality of the first-quartile patients was significantly higher (14 vs. 1.1%, P<0.001). In multivariate Cox's regression analysis for age, sex, diabetes, smoking status, hypertension, hypercholesterolemia, maximum ST depression at TET, angina during TET, coronary artery disease on angiography, and echocardiographic left ventricular ejection fraction, the first quartile of M-score values was found to be independently associated with the composite endpoint (relative risk = 3.26, 95% confidence interval = 2.01-5.29, P<0.001). CONCLUSION: This study shows that a new index termed the M score, which incorporates QRS score and exercise duration, predicts mortality and occurrence of myocardial infarction at long-term follow-up of high-risk individuals, independently of TET-induced ST-segment changes.

Intracardiac echocardiography-facilitated ablation of a left-lateral bypass tract in a patient with atrial septal aneurysm.

Intracardiac echocardiography (ICE) has been used as an adjunctive tool during electrophysiological procedures, mainly to increase the safety of transseptal puncture. We present the case of a young patient with a left-lateral bypass tract and atrial septal aneurysm, in whom ICE delineated the underlying anatomy, excluded the presence of thrombus and facilitated access to the left atrium through a small atrial septal defect, avoiding the risk of needle puncture for interatrial septal crossing.

Correlation of modification of heart rate recovery with adaptation to myocardial ischemia in a model of sequential exercise testings.

BACKGROUND: Heart rate recovery (HRR) has been identified as a reliable predictor of cardiac mortality, correlated with autonomic tone. In a model of sequential exercise testings, we investigated the reproducibility of HRR and the association between HRR modification and myocardial adaptation to ischemia. METHODS: We studied 128 patients (mean age 62 +/- 9 years, 83% males) with angiographically documented coronary artery disease (CAD) and a first positive exercise testing, who agreed to undergo a second exercise testing after 24 hours. RESULTS: HRR was increased from 25 +/- 10 beats/min at the first exercise testing to 30 +/- 13 beats/min at the second exercise testing (P < 0.001). Thereafter, participants were divided into two groups: Group I comprised 88 patients who presented augmentation of the HRR in the first compared to the second exercise testing, while group II comprised 40 patients who presented unchanged or reduced HRR. The rate-pressure product (RPP) at 1 mm ST-segment depression (ischemic threshold) at the second compared to the first exercise testing were significantly improved in group I patients (2345 +/- 3429 mmHg/min), while it was worsened in group II patients (-630 +/- 2510 mmHg/min) (P < 0.001). CONCLUSIONS: In a model of sequential exercise testings, myocardial adaptation to exercise-induced ischemia was associated with favorable modification of HRR.

Modification of cardiometabolic risk through cannabinoid type-1 receptor antagonism.

Large-scale epidemiological studies show that hypertension, diabetes, and dyslipidaemia are highly prevalent among obese individuals. Regrettably, preventive efforts have failed to abolish the increasing prevalence of obesity worldwide. The endocannabinoid system is implicated in the regulation of appetite, food intake, lipids, and glucose metabolism. Rimonabant is the first type-1 endocannabinoid receptor blocker that has been shown to improve the serum lipid profile, insulin and glucose levels, and blood pressure. In particular, the RIO (rimonabant in obesity) studies documented the beneficial metabolic effects of rimonabant. These favorable metabolic effects exceed by about 50% those anticipated by weight reduction, possibly due to modulation of the endocannabinoid system in peripheral tissues. The beneficial effects, however, seem to come at the cost of an increased risk of psychiatric disorders. However, given the efficacy of this treatment and the magnitude of the obesity problem, rimonabant may prove to be a valuable adjunct in targeting obesity-related cardiovascular risk factors.

Alternate site pacing in patients at risk for heart failure.

Cardiac pacing from the right ventricular apex is the most common site of cardiac pacing. During the last decade, several studies demonstrated the harmful effects of the iatrogenic left bundle branch block, which is observed in cardiac pacing from the right ventricular apex. These observations led to an interest in alternative right ventricular pacing sites aiming to achieve a more "physiological" pattern of ventricular activation. Alternate site pacing may involve His bun- dle, other right ventricular sites (outflow or septal sites), or left ventricular sites in either unifocal or bifocal or biventricular modes. Pacing from the right ventricular outflow tract has been studied extensively. Several studies showed that right ventricular outflow tract pacing has better hemodynamic effects and less harmful influence. Bifocal right ventricular (apical and outflow tract) pacing has been proposed for patients with heart failure where the coronary sinus approach to effect biventricular pacing turns out to be unsuccessful because of various reasons. Some studies examined left ventricular pacing alone as an alternative mode of pacing, and the results were quite encouraging but not conclusive. Finally, in heart failure patients not responding to biventricular pacing, the triple site pacing mode has been recently proposed. In triple site pacing, the leads are inserted in the right ventricular apex and outflow tract in conjunction with lateral left ventricular pacing. Improvement of exercise capacity and increased ejection fraction were observed with this triventricular pacing. Although more data from specifically designed randomized studies are needed, there are many alternative pacing sites, especially for patients at high risk of heart failure, which seems to be less harmful and better tolerated by the patients.

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction.

BACKGROUND: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. METHODS: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. RESULTS: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77-1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63-2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29-4.04, P = 0.908). CONCLUSION: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AMI.

Multiple cardiac metastases from a malignant melanoma.

Metastatic tumors in the pericardium or the heart are more common than primary tumors and their incidence has increased during the last decades due to the prolonged survival of patients with cancer and the increased prevalence of the disease in the general population. We present the case of a 36-year-old patient admitted to our hospital due to fatigue, dyspnea, and episodes of dizziness and fainting during the last month. He had a history of a malignant skin melanoma surgically removed 4 years ago. The echo study identified multiple metastases in the heart involving the pericardium, the myocardium and the right atrium, where the tumor was mobile creating mechanical tricuspid valve stenosis. Malignant metastasis was confirmed by pericardiocentesis and, although treatment with chemotherapy was promptly initiated, the patient died 4 months later. Despite the difficulty in clinical diagnosis of cardiac melanoma, early detection has important therapeutic and prognostic implications. Echocardiography is the most common diagnostic modality and transesophageal approach may be the technique of choice to image intracardiac metastatic tumors.

QRS score improves diagnostic ability of treadmill exercise testing in women.

OBJECTIVE: The accuracy of treadmill exercise testing to detect coronary artery disease is limited in women. This study was undertaken to evaluate whether QRS score can improve the accuracy of treadmill exercise testing in women. METHODS: The study population consisted of 114 women with angina-like symptoms, who underwent both treadmill exercise testing and coronary angiography. The impact of QRS score on the standard ST-segment based diagnostic ability of treadmill exercise testing to detect coronary artery disease was studied. RESULTS: Incorporation of QRS score in standard ST-segment diagnostic criteria significantly enhanced sensitivity (from 59 to 80%), specificity (from 40 to 94%) and diagnostic accuracy (from 50 to 87%) of treadmill exercise testing. The QRS score was shown to reduce significantly the false-positive results from 60 to 6%. Furthermore, QRS score accuracy was correlated with the extent of coronary artery disease. The diagnostic ability of QRS score was greater both among patients with normal and impaired systolic function of the left ventricle. CONCLUSIONS: QRS score can improve the limited diagnostic accuracy of treadmill exercise testing in women, by predominantly decreasing the high prevalence of false-positive results.

Hypertensive patients with false-positive thallium-201 scintigraphic results in the infero-posterior wall are in high risk for coronary artery disease development.

BACKGROUND: It has been previously postulated that Thallium-201 (Tl201) scintigraphy is characterized by relatively low specificity in hypertensive patients. This study was undertaken to assess any possible influence of false-positive scintigraphic results on the prognosis of hypertensive patients. METHODS: The study group comprised 179 consecutive hypertensive patients (128 men and 51 women), aged 50+/-7 years, who underwent exercise Tl(201) scintigraphy and coronary angiography (patients with normal scintigraphic results underwent coronary angiography due to persistent angina-like symptoms). All patients with normal coronary arteries underwent a second Tl201 scintigraphy within 36+/-6 months. Patients with reversible ischemia in the second scintigraphy underwent also a second coronary angiography. RESULTS: Coronary artery disease (CAD) was detected in 78 (44%) patients, while the rest 101 (56%) patients had normal coronary arteries. Abnormal scintigraphic results were revealed in 66 (85%) patients with CAD and in 38 (38%) patients without CAD. Twenty-two (58%) of the 38 hypertensive patients with false-positive scintigraphic results presented reversible ischemia of the infero-posterior wall of the left ventricle. Coronary artery disease was detected in 7 (32%) of these patients during the follow-up period. CONCLUSIONS: Hypertensive patients with normal coronary arteries and false-positive scintigraphic results usually present with reversible ischemia of the infero-posterior wall of the left ventricle. This group of patients seems to be at increased risk of developing CAD in a long-term follow-up period.

The aortic distensibility alteration is an index of influence of ischemic preconditioning to myocardial performance.

BACKGROUND: Ischemic preconditioning (IP) is a cardioprotective phenomenon, induced by brief episodes of myocardial ischemia, which is supposed to affect not only the myocardium, but also the entire cardiovascular system. Considering that patients with coronary artery disease (CAD) have also been described to present impaired aortic mechanical properties, we tried to investigate the possible influence of the late phase of IP on aortic distensibility in patients with CAD. METHODS: Fifty patients, aged 48 to 72 (mean, 57+/-6 years), with angiographically confirmed CAD and exercise-induced myocardial ischemia, underwent two treadmill exercise testings (ETs). The second ETs was performed the next day. Thallium-201 scintigraphy was performed during the first and the second ET. Aortic distensibility was evaluated before each exercise testing by a non-invasive technique, using two-dimensional guided M-mode transthoracic echocardiography and arterial pressure was measured simultaneously at the brachial artery by sphygmomanometry. RESULTS: The patients were divided in 2 groups according to the extent of myocardial ischemia at peak exercise of the second test, compared to the first test. In 35 (70%) of the studied patients ischemia signs were reduced during the second ET (Group A), while in the rest 15 (30%) of the patients (Group B) no improvement or even worsening of the observed ischemia signs was demonstrated by the studied exercise parameters and the extent of myocardial ischemia in thallium-scintigraphy. Increased aortic distensibility during the second measurement was found in 33 (94%) of the 35 patients of Group A but only in 1 (7%) of the 15 patients of Group B. Aortic distensibility was found to be significantly improved in patients of Group A, while it was found to be worsened in Group B patients. CONCLUSIONS: The aortic distensibility alteration could be used as an index of influence of ischemic preconditioning to exercise-induced myocardial ischemia, which could be considered indicative of the systemic effects of IP in humans.