Nonpharmacologic rate control of postoperative atrial fibrillation in the canine sterile pericarditis model.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is common following open heart surgery, and is associated with significant morbidity. Medications used for ventricular rate control of POAF may not be effective in controlling rapid ventricular rates during the postoperative period because of increased sympathetic tone. The purpose of this study was to develop nonpharmacologic rate control of POAF by atrioventricular node (AVN) fat pad stimulation using clinically available temporary pacing wires in the canine sterile pericarditis model. METHODS: We studied 10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-3. The AVN fat pad stimulation (amplitude 2-15 mA; frequency 20 Hz; pulse width 0.03-0.2 ms) was performed during sustained POAF (>5 min). We measured ventricular rate and inefficient ventricular contractions during sustained POAF and compared it with and without AVN fat pad stimulation. Also, the parameters of AVN fat pad stimulation to achieve a rate control of POAF were measured over the postoperative days. RESULTS: Eleven episodes of sustained POAF were induced in 5/10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-2. During POAF, the AVN fat pad stimulation decreased the ventricular rate from 178 ± 52 bpm to 100 ± 8 bpm in nine episodes. Nonpharmacologic rate control therapy successfully controlled the ventricular rate and eliminated inefficient ventricular contractions during POAF for the duration of the AVN fat pad stimulation. The AVN fat pad stimulation output remained relatively stable over the postoperative days. CONCLUSION: During sustained POAF, nonpharmacologic rate control by AVN fat pad stimulation effectively and safely controlled rapid ventricular rates throughout the postoperative period.

The Upper Common Pathway in Atrioventricular Nodal Reentrant Tachycardia: A Comprehensive Review of Evidence and Current Perspectives.

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common form of paroxysmal supraventricular tachycardia, and its diagnostic and therapeutic approaches have been well-established. Traditionally, AVNRT is understood to be an intranodal reentry having two bystander pathways; the upper common pathway (UCP) which connects to the atrium and the lower common pathway which connects to the ventricle. However, the existence of the UCP remains a subject of ongoing debate. The assertion of the UCP's presence is supported by electrophysiological evidence suggesting that the atrium is not essential for the perpetuation of AVNRT. Nonetheless, numerous anatomical studies have failed to identify any structure that could be conclusively designated as the UCP. The histological and electrophysiological characteristics of the slow and fast pathways, which are the core components of AVNRT, suggest the inclusion of atrial myocardium in the reentry circuit. While clear interpretation of these discrepancies remains elusive, potential explanations may be derived from existing evidence and recent research findings concerning the actual AVNRT circuit.

Modern physiological approach to inappropriate ICD shocks due to atrial fibrillation with very fast ventricular response. A case report.

BACKGROUND: Fast-conducting atrial fibrillation misinterpreted as ventricular tachycardia is the leading cause for inappropriate shocks in patients with implantable cardiac defibrillators (ICD). These inappropriate shocks are associated with significant morbidity and mortality and cause great discomfort and stress. CASE PRESENTATION: We report the case of a patient with ischemic cardiomyopathy, permanent atrial fibrillation, and a single-chamber DF-1 ICD implanted for the primary prevention of sudden cardiac death, who presented for multiple inappropriate internal shocks due to very fast-conducting atrial fibrillation, which was mislabeled as ventricular fibrillation by the ICD. Since the patient was under maximal atrioventricular nodal blocking medical therapy (beta-blockers and digitalis) and we didn`t find any reversible causes for the heart rate acceleration, we opted for rate control with atrioventricular node ablation. To counteract the risk of pacing-induced cardiomyopathy in this patient who would become totally pacemaker-dependent, we successfully performed left bundle branch area pacing. Because the patient`s ICD had a DF-1 connection and the battery had a long life remaining, we connected the physiological pacing lead to the IS-1 sense-pace port of the ICD. The 6-month follow-up showed an improvement in left ventricular function with no more inappropriate shocks. CONCLUSIONS: Left bundle branch area pacing and atrioventricular node ablation in patients with an implantable single-chamber DF-1 defibrillator and fast-conducting permanent atrial fibrillation is a cost-efficient and very effective method to prevent and treat inappropriate shocks, avoiding the use of an additional dual-chamber or CRT-D device.

Development of the Cardiac Conduction System.

The electrical impulses that coordinate the sequential, rhythmic contractions of the atria and ventricles are initiated and tightly regulated by the specialized tissues of the cardiac conduction system. In the mature heart, these impulses are generated by the pacemaker cardiomyocytes of the sinoatrial node, propagated through the atria to the atrioventricular node where they are delayed and then rapidly propagated to the atrioventricular bundle, right and left bundle branches, and finally, the peripheral ventricular conduction system. Each of these specialized components arise by complex patterning events during embryonic development. This chapter addresses the origins and transcriptional networks and signaling pathways that drive the development and maintain the function of the cardiac conduction system.

Incidence, clinical characteristics, electrophysiological characteristics and outcomes of patients with baseline PR prolongation undergoing radiofrequency ablation for Atrioventricular nodal reentrant tachycardia.

AIMS AND OBJECTIVES: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia (SVT). Prolonged PR interval(>200 ms) on baseline electrocardiogram (ECG) is uncommon in such patients. The aim of the current study was to evaluate the incidence, clinical, electrophysiological characteristics, and outcomes of patients with baseline prolongation of PR interval undergoing radio-frequency ablation (RFA) for AVNRT. METHODS: Over 10 years, out of the total number of 1435 patients with diagnosed AVNRT, 16 patients had prolonged PR intervals at baseline. All underwent elective RFA. A retrospective analysis of clinical, and electrophysiological characteristics and outcomes was done. The PR interval and atria-ventricular block cycle length values were compared with those patients with a normal interval at baseline and had undergone a successful slow pathway modification for AVNRT. RESULTS: Out of 1435 patients with AVNRT, 16 (0.9 %) patients had baseline PR prolongation on ECG. The mean(+SD) age of the study population was 62.9 + 15.9 years. 10 (62.5 %) were males. The average PR interval was 264.2 + 24.1 ms. Slow fast AVNRT was seen in all. The anatomical site of success for ablation was the lower part of Koch's triangle in all patients. During ablation, a good sustained junctional rhythm was noted in all, with no AV (Atrioventricular) block or PR prolongation noted during ablation in any of the patients. PR interval decreased by more than 20 ms in 10 (62.5 %) patients. AVBCL (AV node block cycle length) increased on an average of 58.7 ms post-ablation. Only one patient developed AV block on follow-up. CONCLUSION: A prolonged PR interval on baseline ECG is uncommon in patients with AVNRT. In these patients, slow pathway modification can be done safely and effectively. AVBCL (AV node block cycle length) increases immediately post-ablation. The risk of AV block though low persists on follow-up.

A case report of right ventricular defibrillator and left bundle branch area leads placement and atrioventricular node ablation with chronic right ventricular thrombus.

Despite lack of concrete evidence, right ventricular thrombus is generally considered to be a contraindication for intracardiac lead placement. We present a case of successful placement of a right ventricular defibrillator lead and left bundle branch pacing lead and atrioventricular node ablation in a patient with chronic right ventricle thrombus.

Conversion to Sinus Rhythm in Refractory Atrial Fibrillation Patients after Atrioventricular Node Ablation with Conduction System Pacing.

Background: "Ablate and pace" strategy is a reasonable treatment option in refractory atrial fibrillation (AF) when sinus rhythm (SR) cannot be achieved with catheter ablation or pharmacological therapy. Atrioventricular node ablation (AVNA) combined with conduction system pacing (CSP), with left bundle branch pacing (LBBP) or His bundle pacing (HBP), is gaining recognition since it offers the most physiological activation of the left ventricle. However, the incidence of conversion to SR after AVNA with CSP is not known. The purpose of the investigation was to determine the incidence of spontaneous conversion to SR and its predicting factors in patients undergoing CSP and AVNA. Methods: Consecutive refractory symptomatic AF patients undergoing AVNA with CSP at our institution between June 2018 and December 2022 were retrospectively analyzed. Twelve lead electrocardiogram (ECG) recordings were analyzed at each outpatient follow-up visit. Echocardiographic and clinical parameters were assessed at baseline and six months after the implantation. Results: Sixty-eight patients (male 42.6%, age 71 ± 8 years, left ventricular ejection fraction 40 ± 15%) were included. Thirty-seven patients (54.4%) received HBP and 31 (45.6%) LBBP. During follow-up, spontaneous conversion to SR was registered in 6 patients (8.8%); 3 in the HBP group and 3 in the LBBP group. Baseline characteristics of patients who converted to SR did not differ from non-sinus rhythm (NSR) patients except for left atrial volume index (LAVI), which was significantly smaller in the SR group (45 mL/ m 2 (41-51) vs. 60 mL/ m 2 (52-75); p = 0.002). Multiple regression model confirmed an inverse association between LAVI and conversion to SR even after considering other clinically relevant covariates (odds ratio 1.273, p = 0.028). At follow-up, LAVI did not change in any group (SR: p = 0.345; NSR: p = 0.508). Improvement in New York Heart Association (NYHA) class was comparable in both groups. Conclusions: Spontaneous conversion to SR after AVNA combined with CSP is not uncommon, especially in patients with smaller left atria. Further studies are warranted to clarify which patients should be considered for initial dual-chamber device implantation to provide atrio-ventricular synchrony in case of SR restoration.

Comparison of Conventionally Performed and Intracardiac Echocardiography Guided Catheter Ablation of Atrioventricular Node in Patients with Permanent Atrial Fibrillation-A Retrospective Single-Center Study.

Background: Atrioventricular node (AVN) ablation is an effective treatment for atrial fibrillation (AF) with uncontrolled ventricular rates despite maximal pharmacological treatment. Intracardiac echocardiography (ICE) can help with visualizing structures, positioning catheters, and guiding the ablation procedure. We compared only fluoroscopy-guided and ICE-guided AVN ablation regarding patients with permanent AF. Methods: Sixty-two consecutive patients underwent AVN ablation were enrolled in our retrospective single-center study (ICE group: 28 patients, Standard group: 34 patients). Procedural data, acute and long-term success rate, and complications were analyzed. Results: ICE guidance for AVN ablation significantly reduced fluoroscopy time (0.30 [0.06; 0.85] min vs. 7.95 [3.23; 6.59] min, p < 0.01), first-to-last ablation time (4 [2; 16.3] min vs. 26.5 [2.3; 72.5] min, p = 0.02), and in-procedure time (40 [34; 55] min vs. 60 [45; 110], p = 0.02). There was no difference in either the total ablation time (199 [91; 436] s vs. 294 [110; 659] s, p = 0.22) or in total ablation energy (8272 [4004; 14,651] J vs. 6065 [2708; 16,406] J, p = 0.28). The acute success rate was similar (ICE: 100% vs. Standard: 94%, p = 0.49) between the groups. Conclusions: In our retrospective trial, ICE-guided AVN ablation reduced fluoroscopy time, procedure time, and first-to-last ablation time. There was no difference in ablation time, total ablation energy, acute and long-term success, and complication rate.

Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.

INTRODUCTION: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output. AREAS COVERED: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field. EXPERT OPINION: Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an If specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.

Predictors of permanent pacemaker implantation following transcatheter aortic valve replacement-the search is still on!

Several anatomical, demographic, clinical, electrocardiographic, procedural, and valve-related variables can be used to predict the probability of developing conduction abnormalities after transcatheter aortic valve replacement (TAVR) that necessitate permanent pacemaker (PPM) implantation. These variables include calcifications around the device landing zone and in the mitral annulus; pre-existing electrocardiographic abnormalities such as left and right bundle branch blocks (BBB), first- and second-degree atrioventricular blocks, as well as bifascicular and trifascicular blocks; male sex; diabetes mellitus (DM); hypertension; history of atrial fibrillation; renal failure; dementia; and use of self-expanding valves. The current study supports existing literature by demonstrating that type 2 DM and baseline right BBB are significant predictors of PPM implantation post-TAVR. Regardless of the side of the BBB, this study demonstrated, for the first time, a linear association between the incidence of PPM implantation post-TAVR and every 20 ms increase in baseline QRS duration (above 100 ms). After a 1-year follow-up, patients who received PPM post-TAVR had a higher rate of hospitalization for heart failure and nonfatal myocardial infarction.

Single-center experience of efficacy and safety of atrioventricular node ablation after left bundle branch area pacing for the management of atrial fibrillation.

BACKGROUND: Atrioventricular node ablation (AVNA) with permanent pacing is an effective treatment of symptomatic atrial fibrillation (AF). Left bundle branch area pacing (LBBAP) prevents cardiac dyssynchrony associated with right ventricular pacing and could prevent worsening of heart failure (HF). METHODS: In this retrospective monocentric study, all patients who received AVNA procedure with LBBAP were consecutively included. AVNA procedure data, electrical and echocardiographic parameters at 6 months, and clinical outcomes at 1 year were studied and compared to a matched cohort of patients who received AVNA procedure with conventional pacing between 2010 and 2023. RESULTS: Seventy-five AVNA procedures associated with LBBAP were studied. AVNA in this context was feasible, with a success rate of 98.7% at first ablation, and safe without any complications. There was no threshold rise at follow-up. At 1 year, 6 (8%) patients were hospitalized for HF and 2 (2.7%) were deceased. Patients had a significant improvement in NYHA class and left ventricular ejection fraction (LVEF) (P ≤ 0.0001). When compared to a matched cohort of patients with AVNA and conventional pacing, AVNA data and pacing complications rates were similar. Patients with LBBAP had a better improvement of LVEF (+5.27 ± 9.62% vs. -0.48 ± 14%, P = 0.01), and a lower 1-year rate of composite outcome of hospitalization for HF or death (HR 0.39, 95% CI: 0.16-0.95, P = 0.037), significant on survival analysis (log-rank P-value = 0.03). CONCLUSION: AVNA with LBBAP in patients with symptomatic AF is feasible, safe, and efficient. Hospitalization for HF or death rate was significantly lower and LVEF improvement was greater.

Beyond the lens: Unveiling the invisible atrioventricular node in the era of high-density mapping.

Numerous studies have clarified the histological characteristics of the area surrounding the atrioventricular (AV) node, commonly referred to as the triangle of Koch (ToK). Although it is suggested that the conduction of electric impulses from the atria to the ventricles via the AV node involves myocytes possessing distinct conduction properties and gap junction proteins, a comprehensive understanding of this complex conduction has not been fully established. Moreover, although various pathways have been proposed for both anterograde and retrograde conduction during atrioventricular nodal reentrant tachycardia (AVNRT), the reentrant circuits of AVNRT are not fully elucidated. Therefore, the slow pathway ablation for AVNRT has been conventionally performed, targeting both its anatomical location and slow pathway potential obtained during sinus rhythm. Recently, advancements in high-density three-dimensional (3D) mapping systems have facilitated the acquisition of more detailed electrophysiological potentials within the ToK. Several studies have indicated that the activation pattern, the low-voltage area within the ToK obtained during sinus rhythm, and the fractionated potentials acquired during tachycardia may be optimal targets for slow pathway ablation. This review provides an overview of the tissue surrounding the AV node as reported to date and summarizes the current understanding of AV conduction and AVNRT circuits. Furthermore, we discuss recent findings on slow pathway ablation utilizing high-density 3D mapping systems, exploring strategies for optimal slow pathway ablation.

A jump in the atrioventricular conduction curve is not caused by a switch from fast pathway to slow pathway conduction.

Background: A jump in the atrioventricular (AV) conduction curve is the current clinical criterion of dual-pathway electrophysiology. However, the assumption that a jump indicates a switch from fast pathway (FP) to slow pathway (SP) conduction remains unconfirmed. This study was carried out to investigate whether a jump indeed indicates a transition from FP to SP conduction, and if not, what the potential cause is. Methods: Eighty-one experimental records from rabbit AV nodal preparations containing the following data were analyzed: 1) had at least one AV conduction curve and 2) had recording of His electrogram alternans (a validated new index of dual-pathway conduction). Most cases also had intracellular action potential recordings from the AV nodal fibers. Results: Of the 81 preparations, 11 (13%) showed a jump in the AV conduction curve. The jumps always occurred after the FP to SP transition. The FP-SP transition occurred at prematurity at 196 ± 39 ms versus the jump at 114 ± 13 ms (p < 0.001). The beat with a jump showed an SP-FP pattern in seven and an SP-SP pattern in four preparations. The jumps were always associated with and most likely caused by the formation of intranodal/nodal-atrial reentry and its subsequent conduction, rather than a switch from FP to SP conduction. Conclusion: Contrary to what has been assumed, a transition from FP to SP conduction does not produce a jump in the AV conduction curve. A jump in the AV conduction curve is most likely caused by the formation of intranodal/nodal-atrial reentry and its subsequent conduction.

Variations in subtle cystic tumors of the atrioventricular node: Five autopsy cases.

Cystic tumor of the atrioventricular node (CTAVN) is the most common primary cardiac tumor cause of sudden death but is rarely found during forensic autopsy. We present five autopsy cases of sudden death from undiagnosed CTAVN. The tumors varied in their histological appearance, which may be related to their variation in clinical presentation. Some of the cases had been diagnosed with epilepsy before death; it seems that syncopal attacks caused by CTAVN may be misdiagnosed as epilepsy. When performing forensic autopsy, CTAVN should be considered in the differential diagnosis of sudden death. Careful examination of the cardiac conduction system is important in every sudden death case regardless of age.

Fetal cystic and solid tumor of the atrioventricular node: Autopsy diagnosis at 12 weeks of gestational age.

Primary cardiac tumors are uncommon clinical entities with an incidence of 0.0017% to 0.03% of all autopsies. Cystic tumor of the atrioventricular node (CTAVN) comprises of 2.7% of cardiac tumors causing sudden death associated with complete heart block. CTAVN is a congenital benign cystic and solid mass located in the triangle of Koch in atrioventricular nodal region of the heart. It has been described from infancy to adulthood, most often as an incidental finding at autopsy, but has been not yet described in fetuses. We report a case of late spontaneous abortion detected during the first ultrasound follow-up consultation at 12w+1d of gestation in a healthy 23-year-old pregnant woman, gravida 2 para 0 and one previous termination of pregnancy. Pathological study of abortion product was request. No abnormalities were detected on gross examination, but microscopically, characteristics features of cardiac cystic and solid tumor of the atrioventricular node were identified. We present the first case described in literature of a congenital benign CTAVN in a non-macerate, normal, female fetus with an appropriate growth and development for 12w+1d of gestational age. There are many reasons for performing a fetal post-mortem autopsy foremost of which is identifying an accurate cause of death.

Systemic Diseases and Heart Block.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

His bundle pacing versus left bundle branch area pacing in patients undergoing atrioventricular node ablation: A prospective and comparative study.

BACKGROUND: Pacemaker implantation combined with atrioventricular node ablation (AVNA) is a well-established strategy for uncontrolled atrial arrhythmias. Limited data are available regarding His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) in this setting. AIM: To compare the outcomes of HBP and LBBAP in patients undergoing pacemaker implantation combined with AVN in routine clinical practice. METHODS: We prospectively included all patients who underwent AVNA after successful conduction system pacing (CSP) in two hospitals between September 2017 and May 2023. The primary outcome was the 1-year composite of first episode of heart failure hospitalization, symptomatic atrioventricular node reconduction requiring a second AVNA procedure, lead revision or death from any cause. RESULTS: A total of 164 patients underwent AVNA following successful CSP (68 HBP and 96 LBBAP). Mean pacemaker implantation and AVNA procedure times were shorter in the LBBAP group than the HBP group (46±18 vs 59±23min; P<0.001 and 31±12 vs 43±22min, respectively; P<0.001). Complete atrioventricular block was more frequently obtained in the LBBAP group (88/96 patients [92%] vs 54/68 patients [79%]; P=0.04). One-year freedom from the composite outcome was more frequent in the LBBAP group (89.7% vs 72.9%; hazard ratio 0.32, 95% confidence interval 0.14-0.72; P=0.01). The strategy was similarly effective in both groups with a significant improvement in NYHA class and left ventricular ejection fraction. A secondary pacing threshold elevation >1V occurred only in the HBP group (11%). CONCLUSION: In this prospective, comparative study, LBBAP provided better 1-year outcomes than HBP.

ECG-based estimation of respiration-induced autonomic modulation of AV nodal conduction during atrial fibrillation.

Introduction: Information about autonomic nervous system (ANS) activity may offer insights about atrial fibrillation (AF) progression and support personalized AF treatment but is not easily accessible from the ECG. In this study, we propose a new approach for ECG-based assessment of respiratory modulation in atrioventricular (AV) nodal refractory period and conduction delay. Methods: A 1-dimensional convolutional neural network (1D-CNN) was trained to estimate respiratory modulation of AV nodal conduction properties from 1-minute segments of RR series, respiration signals, and atrial fibrillatory rates (AFR) using synthetic data that replicates clinical ECG-derived data. The synthetic data were generated using a network model of the AV node and 4 million unique model parameter sets. The 1D-CNN was then used to analyze respiratory modulation in clinical deep breathing test data of 28 patients in AF, where an ECG-derived respiration signal was extracted using a novel approach based on periodic component analysis. Results: We demonstrated using synthetic data that the 1D-CNN can estimate the respiratory modulation from RR series alone with a Pearson sample correlation of r = 0.805 and that the addition of either respiration signal (r = 0.830), AFR (r = 0.837), or both (r = 0.855) improves the estimation. Discussion: Initial results from analysis of ECG data suggest that our proposed estimate of respiration-induced autonomic modulation, a resp, is reproducible and sufficiently sensitive to monitor changes and detect individual differences. However, further studies are needed to verify the reproducibility, sensitivity, and clinical significance of a resp.

Model-based estimation of AV-nodal refractory period and conduction delay trends from ECG.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, associated with significant burdens to patients and the healthcare system. The atrioventricular (AV) node plays a vital role in regulating heart rate during AF by filtering electrical impulses from the atria. However, it is often insufficient in regards to maintaining a healthy heart rate, thus the AV node properties are modified using rate-control drugs. Moreover, treatment selection during permanent AF is currently done empirically. Quantifying individual differences in diurnal and short-term variability of AV-nodal function could aid in personalized treatment selection. Methods: This study presents a novel methodology for estimating the refractory period (RP) and conduction delay (CD) trends, and their uncertainty in the two pathways of the AV node during 24 h using non-invasive data. This was achieved by utilizing a network model together with a problem-specific genetic algorithm and an approximate Bayesian computation algorithm. Diurnal variability in the estimated RP and CD was quantified by the difference between the daytime and nighttime estimates, and short-term variability was quantified by the Kolmogorov-Smirnov distance between adjacent 10-min segments in the 24-h trends. Additionally, the predictive value of the derived parameter trends regarding drug outcome was investigated using several machine learning tools. Results: Holter electrocardiograms from 51 patients with permanent AF during baseline were analyzed, and the predictive power of variations in RP and CD on the resulting heart rate reduction after treatment with four rate control drugs was investigated. Diurnal variability yielded no correlation to treatment outcome, and no prediction of drug outcome was possible using the machine learning tools. However, a correlation between the short-term variability for the RP and CD in the fast pathway and resulting heart rate reduction during treatment with metoprolol (ρ = 0.48, p < 0.005 in RP, ρ = 0.35, p < 0.05 in CD) were found. Discussion: The proposed methodology enables non-invasive estimation of the AV node properties during 24 h, which-indicated by the correlation between the short-term variability and heart rate reduction-may have the potential to assist in treatment selection.