The changing circumstance of atrial fibrillation - progress towards precision medicine.

The prevalence of atrial fibrillation (AF) in the general population is between 1% and 2% in the developed world and is higher in men than in women. The arrhythmia occurs much more commonly in the elderly, and the estimated lifetime risk of developing AF is one in four for men and women aged 40 years and above. Projected data from multiple population-based studies in the USA and Europe predict a two- to threefold increase in the number of AF patients by 2060. The high lifetime risk of AF and increased longevity underscore the important public health burden posed by this arrhythmia worldwide. AF has multiple aetiologies and a broad variety of presentations. The primary pathologies underlying or promoting the occurrence of AF vary more than for any other cardiac arrhythmia, ranging from autonomic imbalance to organic heart disease and metabolic disorders, such as diabetes mellitus, metabolic syndrome, hyperthyroidism and kidney disease, and lifestyle factors such as smoking, alcohol consumption and participation in endurance sports. Biomarkers are increasingly being investigated and, together with clinical and genetic factors, will eventually lead to a clinically valuable detailed classification of AF which will also incorporate pathophysiological determinants and mechanisms of the arrhythmia. In turn, this will allow the development and application of precision medicine to this troublesome arrhythmia.

A tailored treatment strategy: a modern approach for stroke prevention in patients with atrial fibrillation.

The main priority in atrial fibrillation (AF) management is stroke prevention, following which decisions about rate or rhythm control are focused on the patient, being primarily for management of symptoms. Given that AF is commonly associated with various comorbidities, risk factors such as hypertension, heart failure, diabetes mellitus and sleep apnoea should be actively looked for and managed in a holistic approach to AF management. The objective of this review is to provide an overview of modern AF stroke prevention with a focus on tailored treatment strategies. Biomarkers and genetic factors have been proposed to help identify 'high-risk' patients to be targeted for oral anticoagulation, but ultimately their use must be balanced against that of more simple and practical considerations for everyday use. Current guidelines have directed focus on initial identification of 'truly low-risk' patients with AF, that is those patients with a CHA2 DS2 -VASc [congestive heart failure, hypertension, age ≥75 years (two points), diabetes mellitus, stroke (two points), vascular disease, age 65-74 years, sex category] score of 0 (male) or 1 (female), who do not need any antithrombotic therapy. Subsequently, patients with ≥1 stroke risk factors can be offered effective stroke prevention, that is oral anticoagulation. The SAMe-TT2 R2 [sex female, age <60 years, medical history (>2 comorbidities), treatment (interacting drugs), tobacco use (two points), race non-Caucasian (two points)] score can help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2 R2 score 0-2) or those who are likely to have a poor time in therapeutic range (SAMe-TT2 R2 score >2). A clinically focused tailored approach to assessment and stroke prevention in AF with the use of the CHA2 DS2 VASc, HAS-BLED [hypertension, abnormal renal/liver function (one or two points), stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years) drugs/alcohol concomitantly (one or two points)] and SAMeTT2 R2 scores to evaluate stroke risk, bleeding risk and likelihood of successful warfarin therapy, respectively, is discussed.

What have we learned of ablation procedures for atrial fibrillation?

Atrial fibrillation is a widespread disease of growing clinical, economic and social importance. Interventional therapy for atrial fibrillation offers encouraging results, with pulmonary vein isolation (PVI) as the established cornerstone. Yet, the challenge to create durable transmural lesions remains, leading to recurrence of atrial fibrillation in long-term follow-up even after multiple ablation procedures in 20% of patients with paroxysmal atrial fibrillation and approximately 50% with persistent atrial fibrillation. To overcome these limitations, innovative tools such as the cryoballoon and contact force catheters have been introduced and have demonstrated their potential for safe and effective PVI. Furthermore, advanced pharmacological and pacing manoeuvres enhance evaluation of conduction block in PVI.

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.

Task Force on Sudden Cardiac Death, European Society of Cardiology.

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.

Thoracic epidural anesthesia does not influence the occurrence of postoperative sustained atrial fibrillation.

BACKGROUND: To evaluate whether thoracic epidural anesthesia (TEA) can reduce the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). METHODS: Forty-one patients undergoing CABG were treated with TEA intraoperatively and postoperatively. Another 80 patients served as the control group. The sympathetic and parasympathetic activities were evaluated by analysis of neuropeptides, catecholamines and heart rate variability (HRV), preoperatively and postoperatively. RESULTS: Postoperative AF occurred in 31.7% of the TEA-treated patients and in 36.3% of the untreated patients (p = 0.77). TEA significantly suppressed sympathetic activity, as indicated by a less pronounced increase of norepinephrine and epinephrine (p = 0.03, p = 0.02) and a significant decrease of neuropeptide Y (p = 0.01) postoperatively in TEA-treated patients compared to untreated patients. The HRV variable expressing sympathetic activity was significantly lower and the postoperative increase in heart rate was significantly less in the TEA group than in the control group after surgery (p = 0.01, p < 0.001). Among patients developing AF, the maximal number of supraventricular premature beats per minute increased significantly in untreated patients postoperatively but remained unchanged in TEA-treated patients (p = 0.004 versus p = 0.86). CONCLUSIONS: TEA has no effect on the incidence of postoperative sustained AF, despite a significant reduction in sympathetic activity.

Diminished circadian variation in heart rate variability before surgery in patients developing postoperative atrial fibrillation.

OBJECTIVE: To evaluate the role of the autonomic nervous system for the development of atrial fibrillation (AF) after coronary artery bypass surgery. DESIGN: Eighty patients without a previous history of AF were included. The sympathetic and parasympathetic activity were evaluated by the analysis of heart rate variability (HRV) in the frequency domain from 24-h Holter recordings and by measuring neuropeptides (neuropeptide Y, chromogranin A, chromogranin B, and pancreatic polypeptide (PP)) and catecholamines, obtained pre- and postoperatively. RESULTS: Preoperatively, patients (36.3%) developing AF postoperatively showed a statistically significant less circadian variation in the HRV variables, the high-frequency (HF) component (p = 0.013) and the low-frequency (LF)/HF ratio (p = 0.007), than patients remaining in sinus rhythm. The HF component and PP. both reflecting parasympathetic activity, and all other variables in the frequency domain, decreased significantly after surgery in both patient groups (p < 0.0001). Although catecholamines increased significantly postoperatively in both patient groups, neither catecholamines nor neuropeptides expressing sympathetic activity, differed between the two groups. PP was, however, significantly higher in patients with postoperative AF than in those with sinus rhythm postoperatively on day 1. CONCLUSION: The diminished circadian variation in HRV before surgery and the indirect signs of a higher parasympathetic activity in patients developing postoperative AF compared with patients remaining in sinus rhythm, may indicate a propensity for AF.

Effects of the maze operation on health-related quality of life in patients with atrial fibrillation.

BACKGROUND: Maze surgery for atrial fibrillation (AF) is a curative therapy, but its effect on health-related quality of life has not been studied. METHODS AND RESULTS: Maze operations were performed in 48 patients with drug-refractory AF. The majority of patients (80%) had lone AF, and the primary indication for surgery in all patients was AF. The SF-36 Health Survey was used to assess quality of life before operation and at 6 months and 1 year after surgery. Twenty-five patients were available for the 1-year follow-up and completed all questionnaires. Before maze surgery, the SF-36 scores were significantly lower than in the general Swedish population, reflecting significant impairment in well-being, physical and social functioning, and mental health. After maze surgery, the quality of life was significantly improved at 6 months and at 1 year on all scales except for bodily pain, which, however, was not significantly decreased before surgery. At both 6 months and 1 year after maze surgery, quality of life, measured by the SF-36, reached the levels of the general Swedish population. CONCLUSIONS: The maze operation can significantly improve the health-related quality of life in selected groups of patients with both paroxysmal and chronic AF refractory to antiarrhythmic therapy.

The value of predischarge ICD tests in patients with a successful peroperative test.

An internal cardioverter defibrillator (ICD) is normally extensively tested during implantation. The necessity of retesting prior to discharge of the patient is a matter of debate. In our material of 30 patients undergoing first-time implantation of a transvenous internal defibrillator system, we retrospectively compare the predischarge defibrillation test with the peroperative test. A successful peroperative defibrillation test with no failed shocks at 10 J below maximal energy level was followed by a successful predischarge test with the same safety margin in 18/19 patients, while one patient required a maximal energy ICD shock for conversion at the predischarge test. We conclude that the predischarge defibrillation test can be omitted if the peroperative test was successful, with no failed shocks at 10 J below maximal energy level and if the shock therapy is set to maximal energy level.

Tachyarrhythmias and triggering factors for atrial fibrillation after coronary artery bypass operations.

BACKGROUND: We evaluated the role of supraventricular arrhythmias and assessed clinical predictors of atrial fibrillation (AF) that developed after coronary artery bypass operations. METHODS: Eighty patients, with a mean age of 65.8 years, underwent 24-hour Holter monitoring preoperatively and for 4 consecutive days postoperatively, or until clinically documented AF, for analysis of the number of premature beats and tachyarrhythmias. Atrial areas and atrial peptides were measured preoperatively and postoperatively. RESULTS: Twenty-nine of 80 (36.3%) patients had postoperative AF. Preoperatively, the maximal supraventricular premature beats per minute were higher in the AF group (p = 0.02). The body mass index and total amount of cardioplegia were lower (p = 0.02 and p = 0.006, respectively), and withdrawal of beta-blockers postoperatively more frequent (p = 0.001) in the AF group, but atrial areas and atrial peptides did not differ. CONCLUSIONS: Frequent supraventricular premature beats preoperatively may indicate a propensity for AF. A larger amount of cardioplegia during the cross-clamp period may reduce the risk of postoperative AF. Further studies are mandatory to clarify why patients with lower body mass index were more prone to AF.

Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q.

Twenty-one members of a Swedish family suffering from myopathy and cardiomyopathy underwent neurological and cardiological investigations. Medical charts of 2 affected deceased patients were reviewed. Twelve patients had myopathy. The distribution of weakness was axial in mildly affected, axial and predominantly distal in moderately affected, and generalized in severely affected patients. The electromyogram showed signs of myopathy in 10 patients. Muscle biopsy specimens showed myopathic changes, rimmed vacuoles, and accumulation of desmin, dystrophin, and other proteins. Electron microscopy revealed granulofilamentous changes and disorganization of myofibrils. Several patients had episodes of chest pain or palpitations. Three men had arrhythmogenic right ventribular cardiomyopathy. Nonsustained ventribular tachycardia, atrial flutter, and dilatation of the ventricles mainly affecting the right ventricle were documented. Two of them had a pacemaker implanted because of atrioventricular block and sick sinus syndrome. Inheritance is autosomal dominant with variable onset and severity of skeletal muscle and cardiac involvement. Linkage analysis of candidate chromosomal regions showed a maximum 2-point LOD score of 2.76 for marker locus D10S1752 on chromosome 10q. A multipoint peak LOD score of 3.06 between markers D10S605 and D10S215 suggests linkage to chromosome 10q22.3, and this region may harbor a genetic defect for myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopahty.

The safety of reusing ablation catheters with temperature control and the need for a validation protocol and guidelines for reprocessing.

The objective of this study was to evaluate the safety of reusing ablation catheters with temperature control, which has not previously been reported. A review of previously conducted studies on the feasibility of reusing electrode catheters is also presented. From September 1994 to December 1997, 74 deflectable ablation catheters with temperature control (Cordis-Websters and Osypkas) were used during mean 7.6 +/- 8.0 ablation sessions. The catheter tests included visual inspection for surface defects using a magnification glass, impedance measurements, evaluation of the catheter deflection capability, and the integrity of the thermistor and thermocouple. The catheters were sterilized by Sterrad after each use. A total of 41 catheters were rejected after an average 9.1 +/- 8.8 uses (range 1-31). The main reasons for rejection were inaccurate temperature measurements by the thermistor or thermocouple (19%), breakage of or defect in the internal pulling wire (12%), loss or disturbance of electrogram (9%), and loss of deflection capability (8%). The reuse of the catheters has not resulted in any major catheter failures or any major adverse clinical complications. There were no local or systemic infections. It can be concluded that these types of ablation catheters will sustain repeated uses and resterilizations without untoward harm to the patient provided that a thorough validation protocol and guidelines for quality control and rejection of catheters are used. There seems to be no rational for setting a limit for the number of reuses, since most failures occurred at any time of reuse.

Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study.

OBJECTIVES: The aim of the present investigation was to redefine the clinicopathologic profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC), with special reference to disease progression and left ventricular (LV) involvement. BACKGROUND: Long-term follow-up data from clinical studies indicate that ARVC is a progressive heart muscle disease that with time may lead to more diffuse right ventricular (RV) involvement and LV abnormalities and culminate in heart failure. METHODS: Forty-two patients (27 male, 15 female; 9 to 65 years old, mean [+/-SD] age 29.6 +/- 18) from six collaborative medical centers, with a pathologic diagnosis of ARVC at autopsy or heart transplantation, and with the whole heart available, were studied according to a specific clinicomorphologic protocol. RESULTS: Thirty-four patients died suddenly (16 during effort); 4 underwent heart transplantation; 2 died as a result of advanced heart failure; and 2 died of other causes. Sudden death was the first sign of disease in 12 patients; the other 30 had palpitations, with syncope in 11, heart failure in 8 and stroke in 3. Twenty-seven patients experienced ventricular arrhythmias (ventricular tachycardia in 17), and 5 received a pacemaker. Ten patients had isolated RV involvement (group A); the remaining 32 (76%) also had fibrofatty LV involvement that was observed histologically only in 15 (group B) and histologically and macroscopically in 17 (group C). Patients in group C were significantly older than those in groups A and B (39 +/- 15 years vs. 20 +/- 8.8 and 25 +/- 9.7 years, respectively), had significantly longer clinical follow-up (9.3 +/- 7.3 years vs. 1.2 +/- 2.1 and 3.4 +/- 2.2 years, respectively) and developed heart failure significantly more often (47% vs. 0 and 0, respectively). Patients in groups B and C had warning symptoms (80% and 87%, respectively, vs. 30%) and clinical ventricular arrhythmias (73% and 82%, respectively, vs. 20%) significantly more often than patients in group A. Hearts from patients in group C weighed significantly more than those from patients in groups A and B (500 +/- 150 g vs. 328 +/- 40 and 380 +/- 95 g, respectively), whereas hearts from both group B and C patients had severe RV thinning (87% and 71%, respectively, vs. 20%) and inflammatory infiltrates (73% and 88%, respectively, vs. 30%) significantly more often than those from group A patients. CONCLUSIONS: LV involvement was found in 76% of hearts with ARVC, was age dependent and was associated with clinical arrhythmic events, more severe cardiomegaly, inflammatory infiltrates and heart failure. ARVC can no longer be regarded as an isolated disease of the right ventricle.

Signed value of monophasic action potential duration difference. A useful measure in evaluation of dispersion of repolarization in patients with ventricular arrhythmias.

AIMS: To evaluate the usefulness of the signed value of monophasic action potential duration difference in analysing the cause of dispersion of ventricular repolarization. METHODS AND RESULTS: Monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 36 patients with ventricular arrhythmias. The time difference between the ends of repolarization on the two monophasic action potentials was used as a measure of the dispersion of ventricular repolarization, and the signed value of the monophasic action potential duration difference was used to specify the contributions of the activation time difference and the monophasic action potential duration difference to the dispersion of ventricular repolarization. During right ventricular pacing, single and double programmed stimulation and at the induction of ventricular arrhythmias, the dispersion of ventricular repolarization and the signed value of monophasic action potential duration difference were markedly greater in the 11 patients with polymorphic ventricular tachycardia/ventricular fibrillation induced than in the 13 patients with monomorphic ventricular tachycardia induced, and in the 10 patients with clinical polymorphic ventricular tachycardia/ventricular fibrillation/cardiac arrest than in the 12 patients with sustained monomorphic ventricular tachycardia. This disclosed that the increased dispersion of ventricular repolarization was caused by increases in both the activation time difference and the monophasic action potential duration difference in the former, but mainly by an increased activation time difference in the latter groups. CONCLUSION: The signed value of monophasic action potential duration difference can specify whether an increased dispersion of ventricular repolarization is caused by inhomogeneous repolarization, inhomogeneous conduction or both, and thereby it is useful in study of the mechanism of ventricular arrhythmias.

Dispersion of repolarization following double and triple programmed stimulation. A clinical study using the monophasic action potential recording technique.

To study the dispersion of ventricular repolarization following double and triple programmed stimulation and its correlation with the inducibility of ventricular arrhythmias, monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 12 patients with ventricular arrhythmias and a normal QT interval. The time difference between the ends of the two monophasic action potentials were used as a measure of the dispersion of ventricular repolarization, which consists of the activation time difference and the monophasic action potential duration difference. During double and triple programmed stimulation, the dispersion of ventricular repolarization increased significantly with the shortening of the coupling interval but decreased slightly with the shortening of the preceding interval. The induction of the ventricular arrhythmias in these patients was invariably associated with a marked increase in the dispersion of ventricular repolarization. The maximal dispersion of ventricular repolarization was significantly larger in the seven patients with polymorphic ventricular tachycardia and/or ventricular flutter/fibrillation induced than in the four patients with monomorphic ventricular tachycardia induced. Analysis of the two components of the dispersion of ventricular repolarization revealed that the increased dispersion of ventricular repolarization was mainly caused by an increase in the activation time difference in the monomorphic ventricular tachycardia subgroup, and by increases in both the activation time difference and monophasic action potential duration difference in the polymorphic ventricular tachycardia/fibrillation subgroup. These findings suggest that increased dispersion of ventricular repolarization is one of the underlying mechanisms accounting for the myocardial vulnerability to ventricular arrhythmias and that repolarization disturbance is important for the genesis of polymorphic ventricular tachycardia/fibrillation.