An update on atrial fibrillation in 2014: From pathophysiology to treatment.

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy.

Cardiac electrophysiology in diabetes.

Patients with diabetes mellitus are at higher risk of cardiac arrhythmias and sudden death. Although there are several animal and human studies on this topic, the pathophysiology of the increased electrical vulnerability in diabetes is complex and remain undefined. It is conceivable that an interplay of several concomitant factors may facilitate the occurrence of arrhythmias. Atherosclerosis as well as microvascular disease, which are increased in diabetic patients, may facilitate myocardial ischemia that predisposes to cardiac arrhythmias and sudden death. In addition, autonomic neuropathy and/or cardiac repolarization abnormalities such as prolonged QT interval and altered T-waves of the diabetic heart also increases electrical instability. Therefore, all these factors may simultaneously contribute to create an electrical instability leading to cardiac arrhythmias and sudden cardiac death. Recently, we have demonstrated that diabetes is the strongest predictor of atrial fibrillation (AF) progression and that diabetic patients frequently have asymptomatic episodes of AF with silent arrhythmia progression. Another recent study has reported that patients with type 2 diabetes and AF are at substantially higher risk of death of any cause compared with those without AF. These seminal studies emphasize that AF in diabetic patients should be regarded as a prognostic marker of adverse outcome and then a prompt aggressive management of all risk factors is required. In conclusion, diabetes mellitus significantly alters the cardiac electrophysiology throughout several complex mechanisms greatly contributing to create an electrical instability of the heart, which may lead to potentially life-threatening arrhythmias and sudden cardiac death.

Role of regional mechanical dyssynchrony as a determinant of functional mitral regurgitation in patients with left ventricular systolic dysfunction.

OBJECTIVE: To assess regional mechanical dyssynchrony as a determinant of the degree of functional mitral regurgitation (FMR). SETTING: Tertiary cardiology clinic. PATIENTS: 74 consecutive patients with left ventricular (LV) dysfunction (ejection fraction < 40%, mean 32.2 (SD 7.3)%) were evaluated. METHODS: Effective regurgitant orifice (ERO) area, indices of mitral deformation (systolic valvular tenting, mitral annular contraction) and of global LV function and remodelling (ejection fraction, end systolic volume, sphericity index) and local remodelling (papillary-fibrosa distance, regional wall motion score index), and tissue Doppler-derived dyssynchrony index (DI) (regional DI, defined as the standard deviation of time to peak myocardial systolic contraction of eight LV segments supporting the papillary muscles attachment) were measured. RESULTS: All the assessed variables correlated significantly with ERO. By multivariate analysis, systolic valvular tenting was the strongest independent predictor of ERO (R(2) = 0.77, p = 0.0001), with a minor influence of papillary-fibrosa distance (R(2) = 0.77, p = 0.01) and regional DI (R(2) = 0.77, p = 0.03). Local LV remodelling (regional wall motion score index: R(2) = 0.58, p = 0.001; papillary-fibrosa distance: R(2) = 0.58, p = 0.002) and global remodelling indices (sphericity index: R(2) = 0.58, p = 0.003) were the main determinants of systolic valvular tenting, whereas regional DI did not enter into the model. Regional DI was an independent predictor of ERO (R(2) = 0.56, p = 0.005) in patients with non-ischaemic LV dysfunction but not in patients with ischaemic LV dysfunction when these groups were analysed separately. CONCLUSIONS: The degree of FMR is associated mainly with mitral deformation indices. The regional dyssynchrony also has an independent association with ERO but with a minor influence; however, it is not a determinant of FMR in patients with ischaemic LV dysfunction.

Radiofrequency catheter ablation in drug refractory maternal supraventricular tachycardias in advanced pregnancy.

BACKGROUND: Treatment of maternal tachyarrhythmias in pregnancy is a major clinical issue. Pharmacological treatment raises important concerns regarding partial efficacy and side effects. Radiofrequency ablation of arrhythmogenic substrate has rarely been performed during pregnancy because of the fetal risks related to x-ray exposure and potential fetomaternal procedural complications. CASES: Three women affected by supraventricular tachycardias refractory to pharmacological therapy underwent successful radiofrequency catheter ablation at 29 to 30 weeks' pregnancy. All patients had cesarean delivery of newborns with normal Apgar scores. CONCLUSION: Radiofrequency catheter ablation is an effective treatment of drug refractory maternal supraventricular tachycardias in advanced pregnancy. Further studies are required to establish its long-term fetal safety.

Heart failure. The pacing therapy.

Several medical therapies, including digoxin, angiotensin-converting enzyme inhibitors, and beta-blockers, have reduced the number of re-hospitalizations and slowed the progression of congestive heart failure (CHF) improving survival. Despite these benefits, medical therapy frequently fails to improve quality of life. Since 1990, there has been a growing interest in using cardiac pacing as additional treatment in severe CHF. Biventricular pacing is used in CHF patients with left bundle branch block (LBBB) to improve ventricular activation sequence which may lead to a more coordinated and efficient ventricular contraction. Since its introduction in CHF in 1994, biventricular pacing has been widely applied with many clinical trials and the development of new specific technology. With the development of new technology, the left ventricular catheterization via a coronary sinus vein, increased from 56% to over 95% during the last 2 years with an acceptable number of complications. Despite encouraging acute and short-term results, pacing strategies for CHF are still limited and currently regarded as investigational. It is clear that while some patients respond remarkably, this is high variable. Clinical trials are currently underway to assess the impact of cardiac resynchronization therapy on morbi-mortality and to assess the association with ventricular defibrillation. The whole validation process of cardiac resynchronization therapy should be completed on 2004-2005. Another novel mode of pacing therapy, which may be clinically appropriate for a broader range of CHF patients irrespective of the presence of LBBB, is contractility modulation, which involves sub-threshold pacing to increase intracellular calcium and enhance inotropy.

Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation.

BACKGROUND: Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). METHODS AND RESULTS: We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001). CONCLUSIONS: Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

[Prospects of the treatment of atrial fibrillation. Circumferential radiofrequency ablation of pulmonary vein ostia]. / Prospettive nel trattamento della fibrillazione atriale. L'ablazione circonferenziale in radiofrequenza degli osti delle vene polmonari.

The dominance of the left atrium (LA) in the pulmonary vein (PV) regions for triggering and maintaining atrial fibrillation (AF) is now widely recognized. Radiofrequency (RF) PV isolation with electroanatomical guidance has recently emerged as a promising approach for AF treatment. We report the clinical outcome of the procedure in 251 consecutive patients with paroxysmal (n = 179) or permanent (n = 72) AF. Circular RF lesions were deployed transseptally during sinus rhythm or AF at 5 mm from PV ostia. Procedural and mapping times were 112 +/- 32 min and 75 +/- 27 min, respectively, with 29 +/- 11 min of fluoroscopy. Complete lesions (peak-to-peak bipolar electrogram amplitude < 0.1 mV inside the line and no double potentials) were achieved in 85% of the veins treated. Sinus rhythm was restored during RF delivery in 52% and by DC shock in the remaining. Major complications (cardiac tamponade) occurred in 3%. Extent of ablated area was 4.9 +/- 0.5 cm2, accounting for 28 +/- 9% of the total LA map surface. After 11 +/- 5 months, procedure success rates (freedom from AF without antiarrhythmic drugs) were 85% for paroxysmal and 68% for permanent AF. No PV stenoses were detected. By univariate analysis, an increased risk of recurrence was predicted by LA dilation (diameter > 50 mm), AF duration, and a low ablated area (< 15% of total LA surface). After adjustment, only the latter variable continued to be significant (odds ratio 3.5, 95% confidence interval, 1.6-5.8). In conclusion, RF PV isolation is safe and effective in either paroxysmal or permanent AF. Patients with enlarged left atrium may require wider lesions to achieve AF suppression.

Fibroma of the left ventricle in a patient with Sotos syndrome.

Primary tumors of the heart are rare, with an incidence between 0.001% and 0.33% in autopsy findings, and with fibromas representing about 4% of benign cardiac tumors. We report the case of a cardiac fibroma in a 5-year-old child affected by Sotos syndrome. The mean sign was a ventricular tachycardia.

Electrical modulation of cardiac contractility: clinical aspects in congestive heart failure.

Heart failure is a highly prevalent disease in western society. Drug therapies aimed at increasing myocardial contractility have been associated with decreased survival. Several short and mid term clinical studies have suggested adjuvant or alternative therapies to congestive heart failure using modified pacing techniques that were aimed to increase contractility (e.g. Paired pacing) or restore synchrony of contraction (biventricular pacing). While delivery of paired pacing was abandoned during the early 70's, biventricular pacing has recently emerged as an adjuvant treatment to limited group of congestive heart failure patients with aberrant left ventricular conduction. In this brief review, we describe our initial safety and efficacy experience in patients with heart failure using a novel non-stimulatory electrical approach to the delivery of positive inotropic therapy to the failing myocardium. The study suggests that unlike modified pacing techniques, delivery of the signal to the left ventricle during the refractory period resulted in a rapid increase in myocardial contractility and improved hemodynamic performance. The near instantaneous contractility improvement achieved by this type of stimulus was shown to be safe and effective independently of the primary cause of heart failure or the function of the conduction system. Unlike pharmacologic treatments, which have a relatively constant effect, use of electrical stimuli may prove useful as a new therapeutic modality in the treatment of heart failure with which contractility can be improved when and as needed.

Pulmonary vein isolation by circumferential radiofrequency lesions in atrial fibrillation. From substrate to clinical outcome.

Circumferential ablation around pulmonary vein ostia by CARTO system was performed in 98 patients with paroxysmal and 29 with permanent atrial fibrillation (AF). Preablation and postablation activation, propagation and voltage maps were obtained. A total of 135 +/- 18 radiofrequency pulses were delivered. After a follow-up of 14.7 +/- 3.3 months, 84 patients with paroxysmal and 22 with chronic AF are in sinus rhythm and 75 of them without antiarrhythmics. Only the area extent of low voltage potentials within and just around the lesions distinguished patients with and without successful ablation. Pulmonary vein isolation is an effective procedure to cure resistant AF; the extent of lesion area around pulmonary vein ostia may be crucial in predicting the outcome.

[Epicardial ablation of atrial fibrillation during heart valve surgery]. / Ablazione epicardica della fibrillazione atriale durante chirurgia valvolare.

BACKGROUND: We report the results of an intraoperative ablation procedure for combined treatment of atrial fibrillation (AF) in patients affected by heart valve disease. METHODS: From February 1998 to June 2000, 80 patients scheduled for heart valve operations underwent combined surgical treatment of AF. Seventy-eight patients had mitral valve disease and 2 had aortic regurgitation; 74 patients were affected by chronic AF (mean 50 +/- 74 months, range 6-480 months) and 6 had paroxysmal AF. A left atrial set of radiofrequency ablations (mainly epicardial) was performed in all patients. RESULTS: Thirty-five patients underwent conservative mitral valve surgery, 43 had mitral valve replacement and 2 had aortic valve replacement. The combination of the ablation procedure did not lead to a substantial prolongation of cardiopulmonary and aortic cross clamp time and did not increase perioperative morbidity. No procedure-related complications were recorded. Operative mortality was favorably comparable with that of valvular surgery alone (2.5%). Mean hospital stay was 6.8 +/- 4.4 days. At follow-up (16.2 +/- 9.2 months, range 3-28 months), 61 patients (78.2%) were in stable sinus rhythm; all of them recovered left and right atrial contractility as assessed by Doppler echocardiography. CONCLUSIONS: The combined treatment of AF with a radiofrequency ablation surgical technique is effective in restoring stable sinus rhythm and atrial contractility. The procedure is low risk thereby allowing a prompt clinical recovery after operation. It should therefore be considered in all patients with AF undergoing open-heart surgery.

QRS complex voltage changes associated with supraventricular tachycardia.

INTRODUCTION: The aim of this study was to evaluate the changes in ventricular complex voltage associated with narrow QRS supraventricular tachycardia (SVT). METHODS AND RESULTS: One hundred forty-five patients undergoing catheter ablation for SVT, 85 with AV nodal reentrant tachycardia (AVNRT) and 60 with AV reentrant tachycardia (AVRT) due to a concealed accessory pathway, were studied. Four consecutive tachycardia beats and four consecutive sinus beats were analyzed, excluding the last tachycardia complex and the first sinus one. For each of the 12 leads, the QRS complex voltage was measured, and the results of four beats were averaged both in SVT and in sinus rhythm (SR). The sum (sigma) of the QRS voltages measured in the 12 leads during SVT (sigmaSVT) and SR (sigmaSR) were calculated, as well as the QRS axis during SVT and SR. QRS complex voltage was significantly increased during SVT, with respect to SR, in leads II, III, aVR, aVF, and V2 to V6. In addition, sigmaSVT was significantly greater than sigmaSR. Only lead V1 showed a significant voltage decrease during SVT. These voltage changes were almost identical in patients with AVNRT and patients with AVRT. No relationship was found between tachycardia rate and QRS voltage variation. The QRS axis showed a significant shift during SVT, from 55.8 degrees to 64.5 degrees. CONCLUSION: QRS voltage increase occurs in reentrant SVT, independent of the underlying reentrant circuit. The phenomenon likely depends on tachycardia-related reduced ventricular filling. This could result in displacement of the heart in such a way that the left ventricle becomes closer to the precordial electrodes (proximity effect). Alternatively, decreased intracavitary blood mass could diminish the intracardiac short-circuiting of potentials, resulting in augmented transmission of cardiac vectors to the body surface.

Acute electrophysiologic effect of estradiol 17beta in menopausal women.

Sixteen postmenopausal women underwent electrophysiologic study before and 20 minutes after the administration of sublingual estradiol 17beta or placebo. Estradiol 17beta significantly affected electrophysiologic parameters, thereby suggesting its role in the development of palpitations in women.

Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families.

BACKGROUND: The ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. METHODS AND RESULTS: Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). CONCLUSIONS: At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation.

BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. METHODS: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

A simple way to treat chronic atrial fibrillation during mitral valve surgery: the epicardial radiofrequency approach.

OBJECTIVE: We describe an original radiofrequency ablation technique to treat chronic atrial fibrillation in patients undergoing mitral valve surgery. Most of the procedure is carried out epicardially, in order to avoid an undue increase of surgical time and trauma. METHODS: The ablations are performed using a temperature-controlled multipolar radiofrequency catheter. Two encircling lesions around the ostia of the right and of the left pulmonary veins are carried out epicardially, usually before cardiopulmonary bypass. Through a conventional left atriotomy the ablation procedure is completed with two endocardial lesions connecting the two encirclings between them and to the mitral valve annulus. After the mitral valve procedure is performed, the left appendage is sutured. RESULTS: From February 1998 to May 1999, 40 patients with chronic atrial fibrillation (43. 1+/-51.9 months) underwent combined radiofrequency ablation and mitral valve surgery. Mean left atrial diameter was 56.8+/-10.7 mm. Mean cardiopulmonary bypass and aortic cross-clamp time were, respectively, 119.1+/-26.3 and 76.7+/-21.0 min. Mean postoperative blood loss was 287.2+/-186.6 ml. No reexploration for bleeding occurred. One patient died of pneumonia 12 days after operation. No patient needed permanent pacemaker implantation. Mean postoperative hospital stay was 7.3+/-5.6 days. At follow-up (mean 11.6+/-4.7 months), 30/39 (76.9%) of the patients were in stable sinus rhythm. All patients in sinus rhythm 3 months after operation recovered both left and right atrial contractility at echocardiographic control (mean 7.3+/-3.4 months). The left atrial diameter decreased significantly in patients recovering sinus rhythm. CONCLUSIONS: Epicardial radiofrequency ablation is a safe means to achieve surgical ablation of atrial fibrillation with a high success rate. The simplicity of the technique and the low procedure-related risk should dictate combined treatment virtually in all patients with atrial fibrillation undergoing open heart operations.

Paroxysmal supraventricular tachycardia caused by 1:2 atrioventricular conduction in the presence of dual atrioventricular nodal pathways.

One-to-two atrioventricular conduction, ie, the double response to a single sinus or atrial impulse, resulting in two QRS complexes for one P wave, is a rare manifestation of dual atrioventricular (AV) nodal pathways. This report describes the case of a 61-year-old woman with continuous episodes of supraventricular tachycardia caused by independent conduction to the ventricles of sinus impulses over both the fast and the slow AV nodal pathway, giving rise to a ventricular rate that was twice the sinus rate. A wide spectrum of electrocardiographic manifestations of 1:2 AV conduction was observed on the surface electrocardiogram. The diagnosis was suggested by several elements including evidence of dual AV nodal pathways during sinus rhythm and cycle length alternans during tachycardia. The patient underwent successful slow pathway ablation with complete disappearance of symptoms and electrocardiographic manifestations of 1:2 AV conduction.