Atrial conduction and atrial fibrillation: What can we learn from surface ECG?

Despite the advancements in pharmacological and non-pharmacological management of atrial fibrillation (AF) observed during last decades, available treatment modalities and predictors of their success are still far from optimal. Understanding of pathophysiological mechanisms underlying AF and assessment of atrial electrophysiological properties using easily available non-invasive diagnostic tools such as surface ECG are essential for further improvement of patient-tailored treatment strategies. P-wave duration is generally accepted as the most reliable non-invasive marker of atrial conduction and its prolongation has been associated with history of AF. However, patients with paroxysmal AF without structural heart disease may not have any impressive P-wave prolongation thus suggesting that the global conduction slowing is not an obligatory requirement for development of AF. In these settings, the morphology of P-wave becomes an important source of information concerning propagation of atrial activation. One of the most common morphologies, i.e. biphasic configuration of P-waves in right precordial leads has been considered a marker of left atrial enlargement but, seen in patients with structurally normal hearts, appears to be linked to an interatrial conduction defect. Recent advances in endocardial mapping technologies have linked certain P-wave morphologies with interatrial conduction patterns that may have clinical implications for invasive treatment of AF patients. The value of P-wave morphology extends beyond cardiac arrhythmias associated with atrial conduction delay and can be used for prediction of clinical outcome of wide range of cardiovascular disorders such as survival after myocardial infarction or the risk of stroke

Predictors of Ventricular Fibrillation at Reperfusion in Patients With Acute ST-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

Ventricular fibrillation (VF) during reperfusion (rVF) in ST-segment elevation myocardial infarction (STEMI) is an infrequent but serious event that complicates coronary interventions. The aim of this study was to analyze clinical predictors of rVF in an unselected population of patients with STEMI treated with percutaneous coronary intervention (PCI). Consecutive patients with STEMI admitted to a tertiary care hospital for primary PCI from 2007 to 2012 were retrospectively assessed for the presence of rVF. Admission electrocardiograms, stored in a digital format, were analyzed for a maximal ST-segment elevation in a single lead and the sum of ST-segment deviations in all leads. Clinical, electrocardiographic, and angiographic characteristics were tested for associations with rVF using logistic regression analysis. Among 3,724 patients with STEMI admitted from 2007 to 2012, 71 (1.9%) had rVF. In univariate analysis, history of myocardial infarction, aspirin and β-blocker use, VF before PCI, left main coronary artery disease, inferior myocardial infarction localization, symptom-to-balloon time 300 μV, and sum of ST-segment deviations in all leads >1,500 μV were associated with increased risk for rVF. In a multivariate analysis, sum of ST-segment deviations in all leads >1500 μV (odds ratio 3.7, 95% confidence interval 1.45 to 9.41, p = 0.006) before PCI remained an independent predictor of rVF. In-hospital mortality was 18.3% in the rVF group and 3.3% in the group without VF (p <0.001), but rVF was not an independent predictor of in-hospital death. In conclusion, the magnitude of ST-segment elevation before PCI for STEMI independently predicts rVF and should be considered in periprocedural arrhythmic risk assessment. Despite higher in-hospital mortality in patients with rVF, rVF itself has no independent prognostic value for prognosis

Respiratory Modulation in Permanent Atrial Fibrillation

Several studies have shown that the autonomic nervous system (ANS) can induce changes during atrial fibrillation (AF). There is currently a lack of methods for quantifying ANS induced variations during AF. The purpose of this study is to quantify respiratory induced modulation in the f-wave frequency trend. Following qrst-cancellation, the local f-wave frequency is estimated by fitting a harmonic f-wave model signal and a quality index (SQI) is computed based on the model fit. The resulting frequency trend is filtered using a narrow bandpass filter with a center frequency corresponding to the local respiration rate. The magnitude of the respiratory induced f-wave frequency modulation is estimated by the envelope of the filtered frequency trend. The performance of the method is validated using simulations and the method is applied to analyze ECG data from eight patients with permanent AF recorded during 0.125 Hz frequency controlled respiration before and after the full vagal blockade, respectively. Results from simulated data show the magnitude of the respiratory induced f-wave frequency modulation can be estimated with an error of less than = 0.005Hz if the SQI is above 0.45. The signal quality was sufficient for analysis in 7 out of 8 patients. In 4 patients the magnitude decreased and in 3 patients there was no change

Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age.

OBJECTIVES: The purpose of this study was to assess the association between structural changes in human atria, age, and history of atrial fibrillation (AF). BACKGROUND: Development of fibrosis in atrial walls is associated with deterioration of atrial conduction and predisposes to AF in experiment. Human data, however, are scarce, and whether fibrosis is a cause or consequence of AF is not known. METHODS: Medical records for consecutive autopsies were checked for AF history and duration. Atrial specimens from 30 patients (ages 64 ± 12 years) were collected in 3 equal age-matched groups as patients without AF history, with paroxysmal AF, or with permanent AF. Tissue samples were obtained at the level of superior pulmonary veins, inferior pulmonary veins, center of posterior left atrial wall, terminal crest, and Bachmann's bundle. Histology sections were assessed for extent of fibrosis, fatty tissues, and inflammatory infiltration at each location. RESULTS: No correlation was observed between age and fibrosis at any location. Fibrosis extent and fatty infiltration were twofold to threefold higher at all locations in patients with history of AF and correlated with lymphomononuclear infiltration. Patients with permanent AF had greater fibrosis extent than did patients with paroxysmal AF. CONCLUSIONS: In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF

Atrial high rate episodes predict clinical outcome in patients with cardiac resynchronization therapy

OBJECTIVES: Up to 50% of patients qualified for cardiac resynchronization therapy (CRT) have documented atrial fibrillation (AF) prior to CRT-implantation. This finding is associated with worse prognosis but few studies have evaluated the importance of post-implant device-detected AF. This study aimed to assess the prognostic impact of device-detected atrial high rate episodes (AHRE), as a surrogate for atrial fibrillation (AF).DESIGN: Data was retrospectively obtained from consecutive patients receiving CRT. Baseline clinical data and data from CRT device-interrogations, performed at a median of 12.2 months after CRT-implantation, were evaluated with regard to prediction of the composite endpoint of death, heart transplant or appropriate shock therapy. Median follow-up time was 51 months post-implant.RESULTS: The study included 377 patients. Preoperative AF was present in 49% and associated with worse outcome. The cumulative burden of AHRE at 12 months post-implant was an independent predictor of the primary endpoint. During the first 12 months after CRT-implantation, AHRE were detected in 25% of the patients with no preoperative diagnosis of AF. This finding was not associated with worse outcome.CONCLUSIONS: In CRT recipients, the cumulative burden of AHRE during first year of follow-up was associated with worse long-term clinical outcome. Prospective trials are needed to determine if a rhythm control strategy is to be preferred in patients with CRT

ECG-based estimation of respiratory modulation of AV nodal conduction during atrial fibrillation

Information about autonomic nervous system (ANS) activity may be valuable for personalized atrial fibrillation (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 AV nodal refractory period and conduction delay. 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 a ECG-derived respiration signal was extracted using a novel approach based on periodic component analysis. We demonstrated using synthetic data that the 1D-CNN can predict the respiratory modulation from RR series alone ($\rho$ = 0.805) and that the addition of either respiration signal ($\rho$ = 0.830), AFR ($\rho$ = 0.837), or both ($\rho$ = 0.855) improves the prediction. Results from analysis of clinical ECG data of 20 patients with sufficient signal quality suggest that respiratory modulation decreased in response to deep breathing for five patients, increased for five patients, and remained similar for ten patients, indicating a large inter-patient variability.Comment: 20 pages, 7 figures, 5 table

An atrioventricular node model incorporating autonomic tone

The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is needed. One important factor may be differences in the autonomic nervous system (ANS) activity. The atrioventricular (AV) node plays an important role during AF in modulating heart rate. To study the effect of the ANS-induced activity on the AV nodal function in AF, mathematical modelling is a valuable tool. In this study, we present an extended AV node model that incorporates changes in autonomic tone. The extension was guided by a distribution-based sensitivity analysis and incorporates the ANS-induced changes in the refractoriness and conduction delay. Simulated RR series from the extended model driven by atrial impulse series obtained from clinical tilt test data were qualitatively evaluated against clinical RR series in terms of heart rate, RR series variability and RR series irregularity. The changes to the RR series characteristics during head-down tilt were replicated by a 10% decrease in conduction delay, while the changes during head-up tilt were replicated by a 5% decrease in the refractory period and a 10% decrease in the conduction delay. We demonstrate that the model extension is needed to replicate ANS-induced changes during tilt, indicating that the changes in RR series characteristics could not be explained by changes in atrial activity alone

Cardiovascular drug utilization post-implant is related to clinical outcome in heart failure patients receiving cardiac resynchronization therapy

    Background: In select patients with heart failure, cardiac resynchronization therapy (CRT) is the most common complementary treatment besides medical treatment. We aimed to assess the association between post CRT-implant changes in cardiovascular medication and cardiovascular mortality and heart failure hospitalization. Methods: 211 patients on optimal medical therapy eligible for CRT were retrospectively included in this study (72 ± 7 years, 80% male, 66% left bundle branch block, 48% dilated cardiomyopathy and investigated at baseline and after 6 months. Follow-up with medication, biochemical markers and echocardiography was performed and 3-year mortality data was collected. Results: At 6 months post-implant the cohort was divided into two groups; 157 patients had low dosage furosemide treatment (up to 40 mg) and 54 patients were treated with high dosage (&gt; 40 mg). A composite endpoint of heart failure hospitalization and all-cause mortality was evaluated at 30 months (881 ± 267 days) after the 6-month visit. In multivariate Cox regression analysis, pa­tients in the high dose diuretics group had a higher risk of the primary endpoint (HR 1.9 [1.1–3.4], p = 0.033), but treatment with high dose diuretics was not associated with improved clinical symptoms (r = 0.031, p = 0.64). Conclusions: High dosage of loop-diuretics was associated with worse medium-term clinical outcome in CRT treated patients. It is unclear whether there is a direct causality between these associations, or if higher prescribed dosage of loop-diuretics is just a marker of more severe disease. Higher dose loop diuretics do not necessarily improve the symptoms and may be harmful to the patient. Prospective trials are warranted to further elucidate these findings. (Cardiol J 2017; 24, 4: 374–384

Patient-assessed short-term positive response to cardiac resynchronization therapy is an independent predictor of long-term mortality.

Cardiac resynchronization therapy (CRT) has a well-documented positive effect on mortality and heart failure morbidity. The aim of this study was to assess the long-term survival and the predictive value of self-assessed functional status on the long-term prognosis of patients treated with CRT-pacemaker (CRT-P).METHODS AND RESULTS: Data were retrospectively collected from medical records of 446 consecutive patients implanted with CRT-P at a large-volume Swedish tertiary care centre. Primary outcome was all-cause mortality, predictive variables were assessed by log-rank test and univariate cox regression. Three hundred and nine patients had reliable information available on early improvement after implantation and were included in the multivariate analyses. The cohort was followed for a median of 79 months and was similar in baseline characteristics compared with major controlled trials. During follow-up 204 patients died, yearly mortality was 11.7%. Early improvement of self-assessed functional status was a strong independent predictor of survival [hazard ratio, HR 0.59, confidence interval (CI) 0.40-0.87, P = 0.007], together with well-known predictors; NYHA III-IV vs I-II (HR 1.66, CI 1.09-2.536, P = 0.018), age (HR 1.05, CI 1.03-1.08, P < 0.001), male gender (HR 2.0, CI 1.11-3.45, P = 0.021), and loop diuretic use (HR 4.41, CI 1.08-18.02). Patients with early improvement of self-assessed functional status had better 2-year and 5-year survival (P < 0.001).CONCLUSIONS: Real-life patient characteristics and predictors of outcome compare well with those in published prospective trials. Self-assessed functional status is a strong predictor of long-term survival, which may have implications for a more active follow-up of patients without spontaneous improvement

Evaluation of depolarization changes during acute myocardial ischemia by analysis of QRS slopes.

OBJECTIVE: This study evaluates depolarization changes in acute myocardial ischemia by analysis of QRS slopes. METHODS: In 38 patients undergoing elective percutaneous coronary intervention, changes in upward slope between Q and R waves and downward slope between R and S waves (DS) were analyzed. In leads V1 to V3, upward slope of the S wave was additionally analyzed. Ischemia was quantified by myocardial scintigraphy. Also, conventional QRS and ST measures were determined. RESULTS: QRS slope changes correlated significantly with ischemia (for DS: r = 0.71, P < .0001 for extent, and r = 0.73, P < .0001 for severity). Best corresponding correlation for conventional electrocardiogram parameters was the sum of R-wave amplitude change (r = 0.63, P < .0001; r = 0.60, P < .0001) and the sum of ST-segment elevation (r = 0.67, P < .0001; r = 0.73, P < .0001). Prediction of extent and severity of ischemia increased by 12.2% and 7.1% by adding DS to ST. CONCLUSIONS: The downward slope between R and S waves correlates with ischemia and could have potential value in risk stratification in acute ischemia in addition to ST-T analysis