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.

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.

Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure.

Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.

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.

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.

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.

Safety of transvenous right ventricular endomyocardial biopsy guided by two-dimensional echocardiography.

A total of 231 endomyocardial biopsy procedures performed in 74 consecutive patients were evaluated to compare the incidence and nature of complications in procedures guided by fluoroscopy versus those guided by echocardiography. Sixty biopsy procedures were guided by fluoroscopy and 171 by two-dimensional echocardiography. The right interventricular septum was the target site for biopsy sampling in all patients. Clinical signs of myocardial perforation occurred during one (1.7%) procedure guided by fluoroscopy versus two (1.2%) procedures guided by echocardiography. Two cases of interventricular septal perforation were visualized during the echo-guided procedures. The biopsy specimens were judged to be inadequate for diagnosis in 2.2% of the biopsy procedures, all of which were guided by fluoroscopy. The number of samples obtained during a procedure guided by fluoroscopy was lower (mean 2.3 +/- 1.6) (mean +/- 1 SD) than that taken during a procedure guided by echocardiography (mean 4.0 +/- 1.2). Epicardial or pericardial tissue was present in 5.8% of the samples obtained under fluoroscopic guidance, versus 0.7% of the samples obtained using echocardiography (p = 0.0003). It is concluded that although echocardiography seems to provide more accurate and safer guidance for the positioning of the bioptome toward the septum, the presence of epicardium or pericardium in 0.7% of the samples indicates that inadvertent sampling from the right ventricular free wall cannot be avoided.

Clinical value of transesophageal atrial stimulation and recording in patients with arrhythmia-related symptoms or documented supraventricular tachycardia--correlation to clinical history and invasive studies.

The main objective of the present study was to evaluate the clinical applicability of transesophageal atrial stimulation (TAS) and recording with regard to inducibility of supraventricular tachycardia (SVT) in patients with either an ECG-documented paroxysmal SVT or a clinical history of palpitations suggesting this disease. A further objective was to assess the inducibility of SVT and to compare the inducibility by TAS with that obtained by an invasive electrophysiologic study (EPS). A total of 64 patients (aged 13-74 years) with ECG-documented paroxysmal SVT (n = 50) or only a history of palpitations (n = 14) was referred for TAS. Preexcitation was present in 35 patients. The study protocol included single and double extrastimuli delivered at a basic paced interval of 500 ms, and incremental atrial stimulation until a cycle length of 275 ms or a second-degree AV block appeared. In 10 patients atropine intravenously was required for induction. The same protocol was used in 34 of the patients who also underwent invasive EPS. TAS was completed in 56 of 64 patients (88%). In this group SVT was induced during TAS in 84% (47/56). Of patients with ECG-documented tachycardia, clinical tachycardia was induced in 90% (35/39) with ECG-documented regular paroxysmal SVT and in 67% of patients (4/6) with ECG-documented atrial fibrillation. In patients without ECG-documented atrial fibrillation. In patients without ECG-documented tachycardia, clinically relevant arrhythmia was induced in 73% (8/11). In 30 of 32 patients (94%) with an inducible tachycardia during invasive EPS, it was also possible to induce the tachycardia by TAS.(ABSTRACT TRUNCATED AT 250 WORDS)