Rationale and design of the MONITOR-ICD study: a randomized comparison of economic and clinical effects of automatic remote MONITORing versus control in patients with Implantable Cardioverter Defibrillators.

BACKGROUND AND AIMS: Implantable cardioverter defibrillator (ICD) remote follow-up and ICD remote monitoring (RM) are established means of ICD follow-up. The reduction of the number of in-office visits and the time to decision is proven, but the true clinical benefit is still unknown. Cost and cost-effectiveness of RM remain leading issues for its dissemination. The MONITOR-ICD study has been designed to assess costs, cost-effectiveness, and clinical benefits of RM versus standard-care follow-up in a prospective multicenter randomized controlled trial. METHODS AND RESULTS: Patients indicated for single- or dual-chamber ICD are eligible for the study and are implanted an RM-capable Biotronik ICD (Lumax VR-T or Lumax DR-T; Biotronik SE & Co KG, Berlin, Germany). Implantable cardioverter defibrillator programming and alert-based clinical responses in the RM group are highly standardized by protocol. As of December 2011, recruitment has been completed, and 416 patients have been enrolled. Subjects are followed-up for a minimum of 12months and a maximum of 24months, ending in January 2013. Disease-specific costs from a societal perspective have been defined as primary end point and will be compared between RM and standard-care groups. Secondary end points include ICD shocks (including appropriate and inappropriate shocks), cardiovascular hospitalizations and cardiovascular mortality, and additional health economic end points. CONCLUSIONS: The MONITOR-ICD study will be an important randomized RM study to report data on a primary economic end point in 2014. Its results on ICD shocks will add to the currently available evidence on clinical benefit of RM.

A multicenter study of shock pathways for subcutaneous implantable defibrillators.

INTRODUCTION: A purely subcutaneous implantable cardioverter defibrillator (ICD) requires higher energy but may be an effective alternative to transvenous ICDs to deliver lifesaving therapies. OBJECTIVE: To identify combinations of anteroposterior subcutaneous shock pathways and waveforms with defibrillation efficacy comparable to transvenous ICDs. METHODS: Defibrillation testing was performed in 141 patients temporarily implanted with an active can emulator and subcutaneous coil electrodes. The patients were subdivided into 5 groups within 2 study phases. In all groups, a posterior electrode was positioned with its tip close to the spine. In the first study phase, 2 different can locations were evaluated: (1) an inframammary pocket (IM-1-750), or (2) a conventional infraclavicular pocket (IC-1-750). In both cases, a 70 J biphasic shock was used (peak voltage 750 V; 270 µF capacitance). In the second phase, configuration IC-1-750 was enhanced by the addition of a second (parasternal) subcutaneous electrode (IC-2-750). Furthermore, the effects of a different 70 J shock waveform (1,000 V, 160 µF) were evaluated for configurations IM-1-750 and IC-2-750 (becoming IM-1-1000 and IC-2-1000). RESULTS: The proportion of patients satisfying a defibrillation safety margin test of 2 consecutive successes at ≤50 J was 74%, 11%, and 44%, respectively, for the IM-1-750, IC-1-750, and IC-2-750 configurations, and 93% and 86% for the IM-1-1000 and IC-2-1000 configurations. CONCLUSIONS: Defibrillation efficacy comparable to that of a transvenous system was achieved with an anteroposterior subcutaneous ICD configuration, with 160 µF capacitance, 1,000 V, and 70 J output. An infraclavicular pocket location becomes feasible if a parasternal subcutaneous coil is added.

Implantable defibrillators with enhanced detection algorithms: detection performance and safety results from the PainFree SST study.

BACKGROUND: Implantable defibrillators (ICD) are highly effective in reducing arrhythmia-related mortality. ICD shock therapy has been shown to increase psychological distress, health care utilization, and is associated with increased mortality. The Protecta ICDs (Medtronic Inc., Minneapolis, MN, USA) have algorithms designed to reduce unnecessary and inappropriate shock therapy. METHODS AND RESULTS: The PainFree SmartShock™ Technology (PainFree SST) study is a prospective, multicenter, clinical trial with two consecutive phases, a premarket phase safety study and a postmarket phase effectiveness study. We report the results of the PainFree SST safety study. The premarket phase aimed to investigate safety in the first year postimplant, and to determine if the novel algorithms (T-wave discrimination, right ventricular lead noise discrimination and confirmation+) affect appropriate ventricular fibrillation (VF) detection. Patients (total: n = 246 [male 78%, mean age 63 year, primary prevention indication in 76%]) were implanted either with a Protecta XT dual-chamber ICD (n = 114 [46%]) or a defibrillator with cardiac resynchronization therapy (n = 132 [54%]). Appropriate VF detection was measured during VF induction at implantation when the novel algorithms were programmed ON. A two-second delay in VF detection was classified as clinically significant. No delay in VF detection was observed with all algorithms programmed ON. No unanticipated serious adverse device effects occurred during first year postimplant. CONCLUSION: The results of the premarket phase of the PainFree SST trial demonstrate the safety of the Protecta XT defibrillators. Detection of induced VF was not delayed with SmartShock™ algorithms ON.

Workload and usefulness of daily, centralized home monitoring for patients treated with CIEDs: results of the MoniC (Model Project Monitor Centre) prospective multicentre study.

AIM: Automated, daily Home Monitoring (HM) of pacemaker and implantable cardioverter-defibrillator (ICD) patients can improve patient care. Yet, HM introduction to routine clinical practice is challenged by resource allocation for regular HM data review. We tested the feasibility, safety, workload, and clinical usefulness of a centralized HM model consisting of one monitor centre and nine satellite clinics. METHODS AND RESULTS: Having no knowledge about patients' clinical data, a telemonitoring nurse (TN) and a supporting physician at the monitor centre screened and filtered HM data in 62 pacemaker and 59 ICD patients from nine satellite clinics for over 1 year. Basic screening of arrhythmic and technical events required 25.7 min (TN) and 0.7 min (physician) per working day, normalized for 100 patients monitored. Communication of relevant events to satellite clinics per email or phone required additional 4.3 min (TN) and 0.4 min (physician). Telemonitoring nurse also screened for abnormal developments in longitudinal data trends weekly for 3 months after implantation, and then monthly; one patient session lasted 4.0 ± 2.9 min. To handle transmission-gap notifications, TN needed additional 2.8 min daily. Satellite clinics received 231.3 observations from the monitor centre per 100 patients/year, which prompted 86.3 patient contacts or intensive HM screening periods by the satellite clinic itself (37.3% response rate), 51.7 extra follow-up controls (22.3%), and 30.1 clinical interventions (13.0%). CONCLUSION: Centralized HM was feasible, reliable, safe, and clinically useful. Basic screening and communication of relevant arrhythmic and technical events required a total of 30 min (TN) and 1.1 min (physician) daily per 100 patients monitored.

Comparison of phenprocoumon with direct oral anticoagulants in catheter ablation of atrial fibrillation.

Aims: In patients undergoing catheter ablation for atrial fibrillation (AF), direct oral anticoagulants (DOACs) are as effective and safe as the vitamin K antagonist (VKA) warfarin. Phenprocoumon has a different pharmacokinetic profile compared with warfarin and is the most used VKA in Germany. The aim of the study was to compare DOAC with phenprocoumon. Methods and results: In this retrospective single-centre cohort study, 1735 patients who underwent 2219 consecutive catheter ablations for AF between January 2011 and May 2017 were included. All patients were in-hospital for at least 48 h after catheter ablation. The primary outcome was defined as peri-procedural thrombo-embolic events. The secondary outcome was any bleeding according to the International Society on Thrombosis and Haemostasis (ISTH). The mean age of the patients was 63.3 years. Phenprocoumon was prescribed in 929 (42%) of the cases, and in 697 (31%) dabigatran, 399 (18%) rivaroxaban, and 194 (9%) apixaban. During hospitalization, 37 (1.6%) thrombo-embolic events occurred, including 23 transient ischaemic attacks (TIAs). Compared with the use of phenoprocoumon, the use of DOAC was significantly associated with a lower thrombo-embolic risk [16 (1.2%) vs. 21 (2.2%), odds ratio (OR)], 0.5 [95% confidence interval (CI) 0.2-0.9], P = 0.04. No statistically significant association with bleeding risk was observed [phenprocomoun: 122 (13%); DOAC: 163 (12.6%); OR 0.9 (95% CI 0.7-1.2); P = 0.70]. Interruption of oral anticoagulation (OAC) was associated with an increased risk for thrombo-embolic complications [OR 2.2 (1.1-4.3); P = 0.031], and bleeding [OR 2.5 (95% CI 1.8-3.2), P = 0.001]. Conclusion: In patients undergoing catheter ablation for AF, the use of DOAC was associated with a reduced risk of thrombo-embolic events compared with phenprocoumon. Non-interrupted oral anticoagulation (OAC) therapy was associated with a reduced risk of peri-procedural thrombo-embolic and any bleeding complications.

Catheter ablation of recurrent scar-related ventricular tachycardia using electroanatomical mapping and irrigated ablation technology: results of the prospective multicenter Euro-VT-study.

INTRODUCTION: Ventricular tachycardia (VT) late after myocardial infarction is an important contributor to morbidity and mortality. This prospective multicenter study assessed the efficacy and safety of electroanatomical mapping in combination with open-saline irrigated ablation technology for ablation of chronic recurrent mappable and unmappable VT in remote myocardial infarction. METHODS AND RESULTS: In 8 European institutions, 63 patients (89% males) were enrolled in the study. All patients had remote myocardial infarction and presented with a median number of 17 (range 1-380) VTs in the preceding 6 months. Incessant VT was present in 14 patients (22%). Left ventricular ejection fraction measured 30 +/- 13%. A mean of 3 VTs were targeted per patient and 22% of all patients had only unmappable VT. The mean follow-up period was 12 +/- 3 months. A total of 164 VTs were targeted during catheter ablation. Ablation was acutely successful in 51 patients (81%). One patient (1.5%) experienced a major complication with degeneration of VT into ventricular fibrillation necessitating cardiopulmonary resuscitation maneuvers. However, no death occurred acutely or within the first 30 days after catheter ablation. During the follow-up, 19 of the initially successful ablated patients (37%) and 31 of all ablated patients (49%) developed some type of VT recurrence. CONCLUSIONS: The results of this multicenter study demonstrate the high acute success rate and a low complication rate of irrigated tip catheter ablation of all clinical relevant VTs in remote myocardial infarction. However, during the follow-up a relevant number of recurrences occurred.

A randomized controlled trial of secondary prevention of anxiety and distress in a German sample of patients with an implantable cardioverter defibrillator.

OBJECTIVE: To evaluate a minimal, easy, accessible intervention targeting anxiety and reduced quality of life in patients with an implantable cardioverter defibrillator (ICD). An estimated 24% to 87% of patients experience anxiety, and 10% to 15% have reduced quality of life. METHODS: A total of 119 ICD patients were assigned randomly to usual medical aftercare (n = 63) or additional psychological treatment (n = 56) comprising of written information on medical and psychological consequences of an ICD plus 6 months of individual phone counseling. Treatment efficacy was evaluated by comparing T0 (immediately after implantation) and T1 (6 months later) assessments. RESULTS: Although 75% of patients considered the program helpful, age moderated treatment efficacy. As indicated by triple interactions, only in the treatment group, anxiety (HADS-Anxiety, p < .01), psychological distress (SCL-K-9, p < .02), and somatic quality of life (SF-36-PCS, p < .01) improved in ICD patients aged <65 years but deteriorated in older patients (age, 65-75 years). Frequency of ICD discharges was associated with a symptom increase from T0 to T1 in all patients (HADS-Depression, CAQ-Avoidance, and ICD-Constraints; all p < .05). CONCLUSIONS: Our findings confirm that psychological treatments cannot be expected to have uniformly positive effects in ICD patients. Our minimal intervention may have adequately addressed ICD-related concerns in younger patients but may have fostered problems in older patients with fewer concerns. Therefore, our findings warrant custom treatment with particular attention to the elderly as well as patients with frequent ICD discharges.

Assessing acute ventricular volume changes by intracardiac impedance in a chronic heart failure animal model.

BACKGROUND: Implantable device diagnostics may play an essential role in simplifying the care of heart failure patients by providing fundamental insights into their complex clinical patterns. Early recognition of heart failure progression by a continuous hemodynamic monitoring would allow for timely therapeutic interventions to prevent decompensation and hospitalization. In this study, the feasibility of assessing ventricular volume changes by implant-based measurements of intracardiac impedance was tested in a heart failure animal model. METHODS: Heart failure was induced in five minipigs by high-rate pacing over 3 weeks. During a final open-chest examination a graded dobutamine stress test was performed. Stroke volume (SV) was measured by an ultrasonic flow probe at the ascending aorta. End diastolic pressure (EDP) and maximum pressure slope (dP/dtmax) were calculated from a left ventricular microtip catheter signal. Impedance was measured by an implanted pacemaker between biventricular leads. Stroke impedance (SZ) was calculated as the difference between end-systolic and end-diastolic impedance (EDZ). RESULTS: Administration of dobutamine led to an increase in SV (55+/-16%), dP/dtmax (107+/-89%), and SZ (56+/-30%). EDP changed by 37+/-21% whereas EDZ changed by 7.4+/-4%. Significant correlations were found between SZ and SV (r=0.88), and between EDZ and EDP (r=-0.82). CONCLUSION: The strong correlation with SV allows the application of intracardiac impedance measurements for an implant-based continuous monitoring of cardiac function. Impedance may also be used for hemodynamic optimization of cardiac resynchronization therapy.

Intracardiac impedance monitors hemodynamic deterioration in a chronic heart failure pig model.

INTRODUCTION: A large number of heart failure (HF) patients benefit from cardiac resynchronization therapy. Measurements of intrathoracic impedance (ITZ) by implantable devices correlate with intrathoracic fluid content and are used for monitoring lung edema formation in HF patients. However, intrathoracic fluid is only an indirect parameter of cardiac function. We hypothesized that changes in intracardiac impedance correlate with left ventricular (LV) volume changes. Therefore, measurements of intracardiac impedance between a right ventricular lead and a LV lead may be used to monitor long-term changes of LV function. METHODS AND RESULTS: HF was successfully induced in nine mini-pigs by continuous high-rate pacing. Hemodynamic parameters as well as intracardiac impedance and ITZ were measured before HF induction and after 20 +/- 5 days of high-rate pacing. After the pacing period, we found a significant deterioration of hemodynamics, reflected by a reduction of ejection fraction from 71+/-11% to 48+/-7% and an increase of LV end diastolic pressure (EDP) from 12 +/- 4 mmHg to 26 +/- 8 mmHg. Worsening of cardiac function correlated with a significant >30% decrease of end diastolic intracardiac impedance, in accordance with a >20% increase of end diastolic volume (EDV). ITZ decreased by more than 8%. We observed a significant inverse correlation between end diastolic intracardiac impedance and EDP (r =-0.81, P < 0.001). CONCLUSIONS: In this animal model, changes of intracardiac impedance revealed hemodynamic deterioration as reflected by EDV and EDP pressure. Thus, intracardiac impedance is a promising new application to monitor heart failure status within implantable devices.

Stability and cause of anxiety in patients with an implantable cardioverter-defibrillator: a longitudinal two-year follow-up.

OBJECTIVE: Several investigations have found that anxiety disorders often develop in patients with an implantable cardioverter-defibrillator (ICD). This study investigated the inter--and intraindividual stability of anxiety and its relation to ICD activity in patients with an ICD. METHODS: Changes in the psychopathology of 35 patients with an ICD were assessed at the beginning of the trial period and 2.5 years later. Psychometric measures of anxiety were collected. During this period, shocks and antitachycardia pacing were assessed. RESULTS: Anxiety was found to be interindividually stable. We also found a slight, but statistically significant, reduction in trait anxiety and avoidance behavior over time. Patients who experienced shocks or antitachycardia pacing did not differ on psychometric or demographic variables from patients without those events. CONCLUSIONS: Anxiety seems to be interindividually stable in patients with an ICD. We found no connection between anxiety and tachycardia episodes in patients with an ICD.

Initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy.

OBJECTIVES: The purpose of this study was to evaluate an implantable cardioverter-defibrillator (ICD) incorporating biventricular pacing. BACKGROUND: Biventricular pacing improves the symptoms of heart failure, a frequent problem in ICD recipients. METHODS: This prospective multicenter study evaluated the safety and efficacy of an ICD with biventricular pacing. RESULTS: A total of 84 patients with a standard ICD indication, symptomatic heart failure, left ventricular (LV) ejection fraction <35% and a QRS duration >130 ms were included in the trial. In 81 of 84 patients the LV lead was successfully implanted. Patients significantly improved in the 6-min hall-walk test (baseline 304 plus minus 131 m, three months 397 plus minus 142 m, p < 0.001), quality of life (baseline 38.9 plus minus 21.2, three months 26.5 plus minus 21.2, p < 0.001) and the New York Heart Association (NYHA) classification (baseline 2.8 plus minus 0.6, three months 2.2 plus minus 0.5). Left ventricular end-diastolic (from 79.6 plus minus 13.0 mm to 73.6 plus minus 12.9 mm, p = 0.002) and end-systolic (from 68.3 plus minus 13.5 mm to 63.9 plus minus 12.9 mm, p < 0.001) diameter decreased, and fractional shortening increased (from 16 plus minus 6% to 18 plus minus 6%, p = 0.018). Of the patients 26 experienced 472 episodes of spontaneous sustained ventricular tachyarrhythmias. All episodes were successfully terminated except for 16 episodes occurring in a patient with incessant ventricular tachycardia. Biventricular antitachycardia pacing was more effective than right ventricular antitachycardia pacing (p < 0.001). During follow-up (median 185 days, range 12 to 344 days) five patients died from progressive heart failure. CONCLUSIONS: Incorporating biventricular pacing in an ICD is feasible and leads to an improvement of heart failure symptoms. Therefore, this therapy may become an option for patients who need ICD therapy in the presence of severe heart failure.

Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I(Ca,L) and I(to) in rapid atrial pacing in rabbits.

OBJECTIVES: The purpose of the study was to characterize the ionic and molecular mechanisms in the very early phases of electrical remodeling in a rabbit model of rapid atrial pacing (RAP). BACKGROUND: Long-term atrial fibrillation reduces L-type Ca(2+) (I(Ca,L)) and transient outward K(+) (I(to)) currents by transcriptional downregulation of the underlying ionic channels. However, electrical remodeling starts early after the onset of rapid atrial rates. The time course of ion current and channel modulation in these early phases of remodeling is currently unknown. METHODS: Rapid (600 beats/min) right atrial pacing was performed in rabbits. Animals were divided into five groups with pacing durations between 0 and 96 h. Ionic currents were measured by patch clamp techniques; messenger ribonucleic acid (mRNA) and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS: L-type calcium current started to be reduced (by 47%) after 12 h of RAP and continued to decline as pacing continued. Current changes were preceded or paralleled by decreased mRNA expression of the Ca(2+) channel beta subunits CaB2a, CaB2b, and CaB3, whereas significant reductions in the alpha(1) subunit mRNA and protein expression began 24 h after pacing onset. Transient outward potassium current densities were not altered within the first 12 h, but after 24 h, currents were reduced by 48%. Longer pacing periods did not further decrease I(to). Current changes were paralleled by reduced Kv4.3 mRNA expression. Kv4.2, Kv1.4, and the auxiliary subunit KChIP2 were not affected. CONCLUSIONS: L-type calcium current and I(to) are reduced in early phases of electrical remodeling. A major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.

beta3-Adrenergic regulation of an ion channel in the heart-inhibition of the slow delayed rectifier potassium current I(Ks) in guinea pig ventricular myocytes.

OBJECTIVES: I(Ks), the slow component of the delayed rectifier potassium current, underlies a strong beta-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in I(Ks). Recent work has pointed to an opposing biological effect of beta(1)- and beta(3)-adrenoceptors in the heart. However the role of these subtypes in the regulation of cardiac ion channel function is unknown. METHODS: We investigated the effects of beta(1)- and beta(3)-adrenoceptor modulation on I(Ks) in guinea-pig ventricular myocytes, using patch-clamp techniques. RESULTS: Superfusion with 100 nmol/l isoproterenol increased the step current amplitude by 81.3+/-8.0%. In contrast, after block of beta(1)- (1 micromol/l atenolol) and beta(2)-receptors (1 micromol/l ICI118,551), isoproterenol induced a reduction of the step current amplitude by 34.3+/-3.5%. The beta(3)-selective agonist BRL37344 significantly reduced the I(Ks) step current at +70 mV in a concentration-dependent manner (IC(50): 5.01 nmol/l). In the presence of bupranolol (beta(1)-, beta(2)- and beta(3)-adrenoceptor antagonist), the effect of BRL37344 was markedly attenuated, from 27.3+/-5.6% (100 nmol/l BRL37344 alone) to 4.0+/-1.3% (100 nmol/l BRL37344+1 micromol/l bupranolol). BRL37344 (100 micromol/) did not alter current amplitudes of KvLQT1/minK expressed in CHO cells or in Xenopus oocytes, excluding a direct effect of BRL37344 on the channel. 1 micromol/l BRL37344 mildly prolonged action potentials in guinea pig ventricle (APD(90):+7.8%) CONCLUSIONS: We have demonstrated a functional coupling between the beta(3)-adrenoceptor and ion channel function in the mammalian heart. Our findings point to a potential role for beta(3)-adrenoceptors in cardiac electrophysiology and pathophysiology.

Effects of the chromanol HMR 1556 on potassium currents in atrial myocytes.

PURPOSE: The chromanol HMR 1556 is a potent blocker of KvLQT1/minK potassium channels expressed in Xenopus oocytes. The compound is therefore a new class III antiarrhythmic drug with a distinct mechanism of action. However, the effect of HMR 1556 on atrial ion channels and the selectivity of block in the human heart has not been investigated. We tested the effects of HMR 1556 on repolarizing potassium currents in human and guinea pig atrial myocytes. METHODS AND RESULTS: Single atrial myocytes were isolated by enzymatic dissociation. Atrial potassium currents (I(Ks), I(Kr), in guinea pig, I(to), I(Kur), I(K1) in humans) were recorded at 36 degrees C in the whole cell mode of the patch clamp technique. HMR 1556 produced a concentration-dependent and reversible block of I(Ks) with a half maximal concentration (EC(50)) of 6.8 nmol/l. 10 micromol/l HMR 1556 almost completely inhibited I(Ks) (97.2+/-3.2%, n=6). Steady-state activation as well as kinetic properties of the current were not altered by HMR 1556. I(Kr) currents were not affected up to concentrations of 10 micromol/l. HMR 1556 did not inhibit other potassium currents in human atrium: I(to), I(Kur) and the classical inward rectifier potassium current I(K1) were not significantly affected up to concentrations that completely blocked I(Ks) (10 micromol/l). CONCLUSIONS: HMR 1556 is a highly-potent blocker of I(Ks) channels without exerting effects on other potassium currents involved in atrial repolarization. Given the potential advantages of I(Ks) vs. I(Kr) blockade, the drug's new mechanism of action warrants further investigation to clarify its role as an antiarrhythmic agent.

Use of beta-blockers in atrial fibrillation.

Atrial fibrillation is the most common arrhythmia in the general population and is frequently associated with organic heart disease. beta-adrenoceptor antagonists (b-blockers) are very effective in preventing atrial fibrillation after coronary artery bypass surgery. It has been shown recently that the beta-blocker metoprolol controlled release/extended release (CR/XL) is also effective in maintaining sinus rhythm after conversion of atrial fibrillation. There is concern that class I antiarrhythmic drugs, such as quinidine, disopyramide, and flecainide in particular, may increase mortality. The risk of proarrhythmia associated with beta-blocker treatment is very low. Therefore b-blockers, such as metoprolol CR/XL, may be the first line of treatment to maintain sinus rhythm, especially after myocardial infarction and in patients with chronic heart failure and in those with arterial hypertension. In patients with persistent atrial fibrillation, AV-nodal conduction-slowing drugs, such as calcium channel antagonists and beta-blockers are used to control the ventricular rate during atrial fibrillation. Several studies clearly show that beta-blockers alone, or in combination with digoxin are very effective in controlling the ventricular rate at rest and during exercise. beta-blockers are effective in maintaining sinus rhythm and controlling the ventricular rate during atrial fibrillation. Given these effects and their favorable effects on mortality, beta-blockers should be considered as first-line agents in the management of patients with atrial fibrillation.

[Quality of antithrombotic therapy in patients with chronic atrial fibrillation: the AFib Trial]. / Qualität der antithrombotischen Therapie bei chronischem Vorhofflimmern: AFib-Studie.

BACKGROUND: Large randomised studies have definitely shown that oral anticoagulation effectively reduces thromboembolic complications, e.g. stroke, in patients with chronic non-valvular atrial fibrillation (AFib). However, less than 50% of the eligible AFib patients receive anticoagulation, although their risk of thromboembolic disease is increased 5-7 fold as compared to individuals who have a regular sinus rhythm. This is the reason why undertreatment needs to be evaluated and addressed. In Germany, data on the antithrombotic therapy of these patients are sparse, national guidelines are lacking. AIM OF THE STUDY: This prospective cohort study is the first one to evaluate the quality of antithrombotic prevention in two groups of AFib outpatients in two different, socio-demographically comparable regions of Germany (Südbaden and Südwürttemberg) over a period of several years. Quality of care is defined as the percentage of AFib patients in a certain region treated according to international guidelines. If the percentage in both cohorts does not exceed 80%, guidelines are to be developed and implemented in Südwürttemberg on consideration of the specific treatment conditions in this region; their applicability is to be evaluated later. METHODS: Office-based specialists of internal and general medicine are currently recruiting 200 AFib patients in each study region for documentation of their clinical data. Besides the quality of antithrombotic chemoprevention, relevant problems emerging in antithrombotic therapy in an ambulant setting will be identified. In the area of intervention (Südwürttemberg) experts and office-based physicians will exclusively develop evidence-based guidelines and disseminate them among doctors. Six months after the implementation of these guidelines in Südwürttemberg, their influence on prescribing patterns will be determined by comparing the proportion of anticoagulated AFib patients in Südwürttemberg to that of the control cohort (Südbaden). In addition, secondary outcomes of interest include deaths, days of hospitalisation, and incidence of stroke or bleeding episodes for different antithrombotic treatments.

Delayed sodium channel inactivation mimics long QT syndrome 3.

DPI 201-106 delays sodium channel inactivation. Acute administration of DPI 201-106 prolonged the QT interval, provoked spontaneous torsades de pointes in one patient, and facilitated stimulation-induced polymorphic ventricular tachyarrhythmias in two patients. Similar to the observations in animal studies, delaying sodium channel inactivation is a new form of the acquired long QT syndrome, mimicking long QT syndrome type 3.

[Remodeling in atrial fibrillation]. / Remodeling bei Vorhofflimmern.

BACKGROUND: Atrial fibrillation is associated with alterations in atrial electrophysiology that facilitate the initiation and persistence of the arrhythmia. This process was termed electrical remodeling in atrial fibrillation. The underlying cellular and molecular mechanisms have intensively been investigated over the past few years in patients with atrial fibrillation and in different experimental models. The results, that have substantially improved the understanding of the pathophysiology of atrial fibrillation, are reviewed. CELLULAR AND MOLECULAR MECHANISMS: On the cellular level, atrial fibrillation leads to a strong shortening and an impaired rate adaptation of the action potential as well as to changes in action potential morphology. Atrial fibrillation is associated with an altered gene expression of the L-type calcium channel (ICa,L) and of potassium channels (Ito, IK1, IKACh). The molecular mechanisms of intraatrial conduction slowing are less well understood, changes in the expression or distribution of gap junction proteins or a decrease of the fast sodium inward channel (INa) have been reported in some studies. A trigger of initiation for electrical remodeling is an overload of the cytoplasm with Ca2+ and a consecutive decrease of the systolic calcium gradient, furthermore changes in calcium-handling proteins are detectable in atrial fibrillation. CONCLUSION: These changes in the cellular and molecular milieu importantly determine the clinical course and the efficacy of therapeutical interventions in atrial fibrillation. The clinical relevance and potential new therapeutic approaches are discussed in the last part.