Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Exchange biased delta-E effect enables the detection of low frequency pT magnetic fields with simultaneous localization.

Delta-E effect sensors are based on magnetoelectric resonators that detune in a magnetic field due to the delta-E effect of the magnetostrictive material. In recent years, such sensors have shown the potential to detect small amplitude and low-frequency magnetic fields. Yet, they all require external magnetic bias fields for optimal operation, which is highly detrimental to their application. Here, we solve this problem by combining the delta-E effect with exchange biased multilayers and operate the resonator in a low-loss torsion mode. It is comprehensively analyzed experimentally and theoretically using various kinds of models. Due to the exchange bias, no external magnetic bias fields are required, but still low detection limits down to [Formula: see text] at 25 Hz are achieved. The potential of this concept is demonstrated with a new operating scheme that permits simultaneous measurement and localization, which is especially desirable for typical biomedical inverse solution problems. The sensor is localized with a minimum spatial resolution of 1 cm while measuring a low-frequency magnetic test signal that can be well reconstructed. Overall, we demonstrate that this class of magnetic field sensors is a significant step towards first biomedical applications and compact large number sensor arrays.

Coronary vasospasm induced by painful compression of the brachial artery following coronary angiography.

We report the occurrence of coronary vasospasm following forceful compression of the brachial artery after coronary angiography.

Standardised pre-hospital care of acute myocardial infarction patients: MISSION! guidelines applied in practice.

Background. To improve acute myocardial infarction (AMI) care in the region 'Hollands-Midden' (the Netherlands), a standardised guideline-based care program was developed (MISSION!). This study aimed to evaluate the outcome of the pre-hospital part of the MISSION! program and to study potential differences in pre-hospital care between four areas of residency.Methods. Time-to-treatment delays, AMI risk profile, cardiac enzymes, hospital stay, in-hospital mortality, and pre-AMI medication was evaluated in consecutive AMI patients (n=863, 61±13years, 75% male) transferred to the Leiden University Medical Center for primary percutaneous coronary intervention (PCI).Results. Median time interval between onset of symptoms and arrival at the catheterisation laboratory was 150 (interquartile range [IQR] 101-280) minutes. The alert of emergency services to arrival at the hospital time was 48 (IQR 40-60) minutes and the door-to-catheterisation laboratory time was 23 (IQR 13-42) minutes. Despite significant regional differences in ambulance transportation times no difference in total time from onset of symptoms to arrival at the catheterisation room was found. Peak troponin T was 3.33 (IQR 1.23-7.04) µg/l, hospital stay was 2 (IQR 2-3) days and in-hospital mortality was 2.3%. Twelve percent had 0 known risk factors, 30% had one risk factor, 45% two to three risk factors and 13% had four or more risk factors. No significant differences were observed for AMI risk profiles and medication pre-AMI. Conclusions. This study shows that a standardised regional AMI treatment protocol achieved optimal and uniformly distributed pre-hospital performance in the region 'Hollands-Midden', resulting in minimal time delays regardless of area of residence. Hospital stay was short and in-hospital mortality low. Of the patients, 88% had ≥1 modifiable risk factor. (Neth Heart J 2010;18:408-15.).

Dronedarone in patients with atrial fibrillation.

Dronedarone is a recently developed new class III antiarrhythmic drug which possesses electrophysiological properties of all four Vaughan-Williams classes. An important difference with amiodarone is that it does not contain an iodine component and therefore lacks the iodine-related adverse effects. Based on currently available data, dronedarone can not be recommended as first-line therapy for either rhythm or rate control. We recommend to initiate rhythm or rate control with drugs as indicated in the 2006 guidelines of the ESC and other organisations. As amiodarone, dronedarone can be given to patients for whom standard drug therapy is not effective, or limited by (severe) side effects, although it is less effective than amiodarone. Nevertheless, it may be considered to give dronedarone initially to patients who would otherwise have received amiodarone, since the latter has more severe side effects than the former drug. The daily dosage of dronedarone is oral administration, 400 mg twice daily. Dronedarone is contraindicated in patients with impaired left ventricular function (NYHA class III/IV) and haemodynamic instability. (Neth Heart J 2010;18:370-3.).

Selection of patients for cardiac resynchronisation therapy (CRT) in an unselected heart failure population.

BACKGROUND: In patients with chronic heart failure (CHF), the presence of conduction delay across the myocardium is a well-known feature. During recent years an increasing number of CHF patients have been treated with cardiac resynchronisation therapy (CRT). So far in many protocols patients have been selected using the criteria of left ventricular ejection fraction (LVEF) ≤35% concomitant with signs of widening of the QRS on the surface electrocardiogram, either with or without left bundle branch block (LBBB) morphology. METHODS: In this article we discuss which of the patients admitted with CHF to a regular cardiology practice could be candidates for this therapy. Data were obtained from January 2000 to December 2004 on a total of 861 CHF patients, of whom 309 had an LVEF ≤35%. Of these patients, 123 patients showed a QRS width >120 msec, while 81 patient had a QRS width >140 msec. In total, 89 patients had an LBBB morphology on the electrocardiogram, while 21 patients had univentricular pacing devices in situ. In those patients with an LVEF >35%, QRS width was 108±27msec. CONCLUSION: A substantial number of patients presenting with CHF in a regular cardiology practice are suitable candidates for CRT therapy according to currently used criteria of QRS width and LVEF. This number could be increased even more if recent information concerning intraventricular conduction delay in CHF patients with less widening of the QRS complex were to be applied, as judged by echocardiographic techniques.

Practical implications of having a dedicated heart failure programme.

BACKGROUND: The prevalence of heart failure (HF) is gaining epidemic proportions. Recent data stress the importance of multidisciplinary strategies for the management of HF patients, but the practical consequences of such programmes remain unclear. OBJECTIVE: To describe our experience with a dedicated heart failure programme involving two HF nurses and a cardiologist. METHOD: All patients admitted to the cardiology department with NYHA class III-IV heart failure were included. After admission, patients received optimal medical therapy according to current guidelines, and extensive instructions from a dedicated HF nurse. On discharge they were given comprehensive lists of medications and symptoms, and a weighing list. They were advised to call a nurse in case of questions or problems. RESULTS: 861 patients were included: 63% >75 years, 47% with LVEF >45%. From 2000 onwards, the number of patients admitted once a year increased but seemed to level off in 2004. Most phone calls involved weight changes as well as general physical complaints. In 1266 (46%) of calls, the medication change was a consequence of a problem raised by the patient. The nurse received and answered almost all phone calls. CONCLUSION: The patient group will grow substantially during the first years of the programme, but the number of patients seen in the outpatient clinic appears to stabilise after five years. Many issues regarding the care of these patients can be handled by the HF nurse.

Local vascular complications after use of the hemostatic puncture closure device Angio-Seal.

BACKGROUND: As an alternative to manual pressure techniques new systems for achieving arterial hemostasis after cardiac catheterization were developed. Here we report about the diagnosis and therapy of femoral artery complications after use of the closure device Angio-Seal, consisting of an intraarterial anchor and extravascular collagen plug. PATIENTS AND METHODS: Angio-Seal was deployed in 350 patients undergoing cardiac catheterization. Vascular investigations after device application consisted of ankle/brachial-pressure-index measurement, duplex sonography, and angiography. RESULTS: Vascular complications occurred in 10 of 350 patients. In two patients complete occlusions of the superficial femoral artery required immediate vascular surgery. Stenoses of the superficial (five patients) and the common (three patients) femoral arteries were diagnosed in 8 cases. Of these 10 patients eight were obese, in 2 cases there was a further catheterization with Angio-Seal device application via the same femoral approach. Until now six patients underwent successful surgery: in 4 cases the whole Angio-Seal device was located intraarterially, there was 1 case of intima-dissection, and 1 case remained unclear due to a diagnostic delay of 7 months. In three patients with stenoses of the common femoral arteries without hemodynamic relevance no therapy was required. CONCLUSIONS: Occlusions or stenoses of femoral arteries after use of Angio-Seal can be diagnosed easily by duplex sonography. All hemodynamic relevant complications (n = 7 of 350 [2%]) concerned a puncture of superficial femoral arteries. In these patients vascular surgery seems to be an adequate therapy.

Incidence of cutaneous vasoactivity in patients with anemia and pulmonary hypoxia.

BACKGROUND: In cutaneous laser Doppler flow (LDF)-recordings, various forms of flowmotion or vasoactivity can be observed. It is still a matter of dispute, whether flowmotion is a phenomenon of physiological or pathophysiological conditions. Therefore, we tested the hypothesis of increased vasoactivity being typical for patients with various degrees of acute and chronic anemia as well as with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We examined 12 healthy controls, 14 patients with COPD with a PO2 below 60 mmHg, 16 patients with chronic and 7 patients with acute anemia with an Hb below 12 g/dl. We used a simple LDF-technique on the dorsum of the forefoot. The regularity of blood flow frequencies was determined by calculation of the coefficient of variation. RESULTS: Periods without vasoactivity (i.e. constant flow pattern) were 21% in normal controls, 7% in patients with COPD and 2% in patients with acute or chronic anemia. Mean frequencies in the four groups varied between 3.8 and 4.8 cpm, with significant changes only in the group with acute blood loss. However, vasoactivity was significantly more regular in the COPD- and anemia-groups as compared to normal controls, with coefficients of variation of 47.4% for controls, 31.8% for COPD- and 29.3% for chronic and 35.1% for acute anemia-patients. CONCLUSIONS: The present paper shows that cutaneous vasoactivity is more regular in the three examined clinical entities of systemic tissue hypo-oxygenation, i.e. chronic and acute anemia and severe COPD as compared to healthy control subjects. Therefore, we hypothesize that increased vasoactivity constitutes a regulatory defense mechanism in cases of reduced oxygenation, by improving microcirculatory blood flow distribution.

Carotid sinus massage as a diagnostic and therapeutic tool for atrial flutter-fibrillation.

Alterations in vagal tone can influence the atrial fibrillatory process by changing the atrial refractory period. We observed in a patient with paroxysmal atrial fibrillation (AF) that carotid sinus massage (CSM) changed a "coarse" type of fibrillation into a "fine" type, followed by termination of the arrhythmia. Although coincidental conversion of AF into sinus rhythm could not be excluded, we concluded that it is worth while to try CSM in every patient presenting with AF prior to other interventions to restore sinus rhythm.

Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation.

BACKGROUND: Recently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling. METHODS AND RESULTS: Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+(ATP) channels by glibenclamide (10 micromol/kg; n=6) slightly increased the AFI from 95+/-4 to 101+/-5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69+/-14 versus 75+/-15 ms). Volume loading by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks of AF (n=6), but ANF infusion (0.1 to 3.1 microg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134+/-10 to 105+/-6 ms and inversed its physiological rate adaptation. CONCLUSIONS: Electrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.

Electrophysiological effects of acute dilatation in the isolated rabbit heart: cycle length-dependent effects on ventricular refractoriness and conduction velocity.

BACKGROUND: Acute ventricular dilatation has important electrophysiological effects: Dilatation shortens action potential duration and refractoriness without an apparent effect on conduction velocity. These effects have been implicated as a potential mechanism of arrhythmias in patients with congestive failure. Because the influence of cycle length on these phenomena has not been studied, we examined the effects of dilatation during ventricular pacing at cycle lengths from 1000 to 150 ms. METHODS AND RESULTS: Thin epicardial layers were created in isolated, perfused rabbit left ventricles (n=7). A fluid filled latex balloon was secured in the left ventricle to dilate the left ventricle. Mapping was performed with 248 epicardial electrodes. Longitudinal conduction velocity (76+/-1 cm/s; mean+/-SEM) and transverse conduction velocity (26+/-1 cm/s) were not influenced by dilatation at any cycle length. In contrast, the effects of dilatation in decreasing left ventricular effective refractory period (ERP) were significantly greater at shorter drive cycle lengths: The decrease in ERP was 2+/-2 ms (a 1% change) at a drive cycle length of 1000 ms and 18+/-4 ms (a 20% change) at a drive cycle length of 150 ms. In 10 additional intact, isolated perfused rabbit hearts, dilatation decreased ERP to a greater degree during 250 ms drive cycle length pacing than during pacing at 400 ms (25+/-4 versus 16+/-3 ms; P=.01). CONCLUSIONS: Acute dilatation exaggerates the normal rate-dependent shortening of refractoriness but does not influence transverse or longitudinal conduction velocity. This observation suggests that the electrophysiological effects of acute dilatation may be greater during tachycardia than at slower cycle lengths. This may have implications for arrhythmias in patients with congestive heart failure.

Coronary sinus pacing prevents induction of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is due to reentry, and its incidence has been shown to decrease after dual-site atrial or biatrial pacing. We investigated whether a simpler pacing approach via the distal coronary sinus (CSd) could eliminate AF inducibility by high right atrial (HRA) extrastimuli (APDs). We based our hypothesis on our previous observation that AF inducibility by HRA APDs was associated with conduction delays to the posterior triangle of Koch, whereas AF was never induced with CSd APDs, which were associated with minimal intra-atrial conduction delays. METHODS AND RESULTS: Programmed electrical stimulation was performed from the high right atrium and CSd, and bipolar recordings were obtained from the high right atrium, His bundle, posterior triangle of Koch, and coronary sinus. In 13 patients (age, 44+/-18 years), AF was reproducibly induced with a critically timed HRA APD (220+/-22 ms) delivered during HRA pacing. AF was not induced in any of the patients when HRA APDs were delivered during CSd pacing at the same critical coupling intervals. Coronary sinus APDs delivered during HRA pacing also were not associated with AF induction. The APD coupling interval measured at the posterior triangle of Koch during CSd pacing was significantly prolonged compared with the one measured during HRA pacing and AF induction (381+/-58 versus 263+/-37 ms; P<.0001). CONCLUSIONS: We propose that CSd pacing suppresses the propensity of HRA APDs to induce AF by limiting their prematurity at the posterior triangle of Koch and not allowing local conduction delay and local reentry to occur.

Electrophysiology of atrial fibrillation and its prevention by coronary sinus pacing.

Atrial fibrillation (AF) is a re-entrant rhythm, and patients with AF have intra-atrial conduction abnormalities as evidenced by prolonged P-wave duration, abnormal SAECG of P wave, fragmented atrial electrograms and greater intra-atrial conduction delays in response to APDs. Our previous work has proposed that intra-atrial conduction delays and dispersion of refractoriness during extrastimulus testing are site dependent; high right atrial (HRA) stimulation results in marked prolongation of intra-atrial conduction times and AF, whereas distal coronary sinus (CS) stimulation is associated with minimal conduction delays and absence of AF inducibility. Patients with AF induction during HRA stimulation also manifest non-uniform anisotropic conduction in the region of the posterior triangle of Koch. We postulated that if the posterior triangle of Koch is a critical area for re-entry that initiates AF, then prevention of early activation of the posterior triangle may prohibit AF induction by HRA APDs. Distal CS pacing pre-excites the posterior triangle in relation to HRA activation, therefore a subsequent HRA APD will activate the posterior triangle with a longer coupling interval. AF induction by HRA APDs following HRA pacing is prevented when same HRA APDs follow distal CS pacing. We propose that distal CS pacing eliminates the propensity of HRA extrasystoles to induce AF. This observation may have further clinical applicability in AF prevention.

Production of follistatin in porcine endothelial cells: differential regulation by bacterial compounds and the synthetic glucocorticoid RU 28362.

Follistatin (FS) is the specific binding protein of activin; it has a broad tissue distribution and is also found in serum. The ovary has the highest level of FS expression, but ovariectomy does not cause a permanent reduction in the serum FS level. Therefore, the source of FS in serum is still elusive. As a regulatable, nongonadal source of serum FS could influence ovarian and pituitary-derived hormone secretion and thus reproductive function, we searched for a source of extragonadal FS expression that might contribute to the FS protein level in serum. We found that endothelial cells from blood vessels express FS messenger RNA (mRNA) and protein; therefore, we studied the regulation of steady state levels of FS mRNA in porcine endothelial cells from aorta (AEC) and brain microvessels (BMVEC) in tissue culture. For detection of FS mRNA, a specific 32P-radiolabeled antisense probe and a S1-nuclease protection assay were used. FS steady state levels of AEC decreased with time in culture, i.e. postconfluent AEC had lower FS mRNA levels than confluent cultures, which, in turn, had lower FS mRNA levels than subconfluent cell cultures. FS mRNA levels in AEC were induced by increasing concentrations of FCS and stimulated by 30 micrograms/ml endothelial cell growth supplement. FS mRNA levels in AEC and BMVEC increased approximately 20-fold within 4 h during incubation of the cells with 100 nM phorbol 12-myristate, 13-acetate, whereas 0.5 nmol/ml forskolin tested in AEC for between 4-48 h had no significant effect. Furthermore, 0.1 microM ocadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, caused a significant increase in FS mRNA levels. FS mRNA levels in AEC were not significantly affected by various concentrations of porcine FSH, epidermal growth factor, or retinoic acid for between 4-48 h. Treatment of the cells with 0.01-10 micrograms/ml bacterial lipopolysaccharides (LPS) caused a dose-dependent increase (up to 10-fold) in FS mRNA steady state level in AEC, whereas 1-1000 nM RU 28362, a synthetic glucocorticoid, inhibited FS mRNA steady state levels in a dose-dependent manner. The induction of FS mRNA with 1 microgram/ml LPS was completely blocked by 100 nM RU 28362, and the stimulatory effects of LPS were only visible after 4 h of treatment, not after 24 or 48 h. The same effects were observed with BMVEC. We, furthermore, analyzed FS protein secretion of AEC by Western blotting and demonstrated that FS proteins were secreted into the culture medium upon stimulation with LPS. None of these treatments had an obvious effect on the ratio of the two different forms of FS mRNA (FS 344:FS 317). Besides the expression of FS mRNA in AEC and BMVEC, FS mRNA is also expressed in uncultured plexus choroideus epithel and meninges, and FS protein is found in human cerebrospinal fluid. From this study it is concluded that 1) endothelial cells from different tissues produce FS mRNA; 2) the FS mRNA levels of AEC and BMVEC are subjected to regulation by FCS, endothelial cell growth supplement, bacterial LPS, and the glucocorticoid RU 28362; 3) phosphatases and the protein kinase C-dependent, but not the protein kinase A-dependent, pathway are involved in regulating the steady state levels of FS mRNA in AEC and BMVEC; and 4) endothelial cells produce and secrete FS protein and are thus a likely source of FS in serum.

Pathophysiologic substrate for ventricular tachycardia in coronary artery disease and non-ischemic heart disease.

Sustained uniform monomorphic ventricular tachycardia is usually due to abnormalities of conduction, including coronary artery disease and right ventricular dysplasia. These conduction abnormalities are due to non-uniform anisotropy which is characterized by fragmented electrograms. Less is known about the pathophysiologic substrate of sustained ventricular tachycardia in the absence of coronary artery disease or cardiomyopathy.

Unravelling the electrical mysteries of atrial fibrillation.

Animal experiments have confirmed that a short but variable excitable gap is present during induced atrial fibrillation. The existence of this gap allows atrial fibrillation to be locally captured by rapid pacing. An area of up to 4 cm in diameter can be activated by uniform wave fronts propagating away from the site of stimulation, although the size of this area may be limited by intra-atrial conduction block or by collision with fibrillation waves. Rapid pacing can accelerate atrial fibrillation by inducing local re-entry circuits with a cycle length shorter than the pacing interval. During pacing-induced atrial fibrillation in patients undergoing surgery for Wolff-Parkinson-White syndrome, three types of atrial activation have been identified, which vary in their degree of complexity and in the length of their fibrillation intervals. It appears that the spectrum of varying cycle lengths during atrial fibrillation might be explained by a mixture of different sorts of atrial re-entry patterns, comprising purely functional intra-atrial re-entry, random re-entry, anatomical re-entry, and nodal re-entry.

Electrophysiologic mechanisms of perpetuation of atrial fibrillation.

The presence of an excitable gap during atrial fibrillation (AF), although short and variable, may be of potential importance for the development of alternative techniques for termination of AF by rapid pacing. Also the notion that perpetuation of AF may be partly dependent on macroreentry around the natural atrial orifices, may provide a new therapeutic option for the permanent cure of AF by interrupting the anatomical circular pathways in the atria by radiofrequency ablation. In our opinion the rapidly growing understanding of the electrophysiologic mechanisms of AF certainly warrants some optimism about the possibility of cure of AF in the near future without causing too much discomfort and without carrying on unacceptable risk.

Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats.

BACKGROUND: In this study we tested the hypothesis that atrial fibrillation (AF) causes electrophysiological changes of the atrial myocardium which might explain the progressive nature of the arrhythmia. METHODS AND RESULTS: Twelve goats were chronically instrumented with multiple electrodes sutured to the epicardium of both atria. Two to 3 Weeks after implantation, the animals were connected to a fibrillation pacemaker which artificially maintained AF. Whereas during control episodes of AF were short lasting (6 +/- 3 seconds), artificial maintenance of AF resulted in a progressive increase in the duration of AF to become sustained (> 24 hours) after 7.1 +/- 4.8 days (10 of 11 goats). During the first 24 hours of AF the median fibrillation interval shortened from 145 +/- 18 to 108 +/- 8 ms and the inducibility of AF by a single premature stimulus increased from 24% to 76%. The atrial effective refractory period (AERP) shortened from 146 +/- 19 to 95 +/- 20 ms (-35%) (S1S1, 400 ms). At high pacing rates the shortening was less (-12%), pointing to a reversion of the normal adaptation of the AERP to heart rate. In 5 goats, after 2 to 4 weeks of AF, sinus rhythm was restored and all electrophysiological changes were found to be reversible within 1 week. CONCLUSIONS: Artificial maintenance of AF leads to a marked shortening of AERP, a reversion of its physiological rate adaptation, and an increase in rate, inducibility and stability of AF. All these changes were completely reversible within 1 week of sinus rhythm.