EHRA White Paper: knowledge gaps in arrhythmia management-status 2019.

Clinicians accept that there are many unknowns when we make diagnostic and therapeutic decisions. Acceptance of uncertainty is essential for the pursuit of the profession: bedside decisions must often be made on the basis of incomplete evidence. Over the years, physicians sometimes even do not realize anymore which the fundamental gaps in our knowledge are. As clinical scientists, however, we have to halt and consider what we do not know yet, and how we can move forward addressing those unknowns. The European Heart Rhythm Association (EHRA) believes that scanning the field of arrhythmia / cardiac electrophysiology to identify knowledge gaps which are not yet the subject of organized research, should be undertaken on a regular basis. Such a review (White Paper) should concentrate on research which is feasible, realistic, and clinically relevant, and should not deal with futuristic aspirations. It fits with the EHRA mission that these White Papers should be shared on a global basis in order to foster collaborative and needed research which will ultimately lead to better care for our patients. The present EHRA White Paper summarizes knowledge gaps in the management of atrial fibrillation, ventricular tachycardia/sudden death and heart failure.

Right Ventricular Perforation by a Defibrillator Lead Migrating to the Left Breast.

Cardiac perforation after an ICD implantation is a rare complication, with a reported incidence between 0.6-5.2%. Its manifestation might be acute, subacute, or delayed, with an acute perforation occurring within the first 24 hours after implantation, frequently accompanied by severe clinical signs, while subacute and delayed perforations have a more benign progression. Here, we report a case of a 69-year old patient with an acute right ventricular perforation by a defibrillator lead migrating all the way through the pericardium and thoracic wall into the left breast, with an unusually mild and benign clinical course, delaying prompt diagnosis and postponing subsequent surgical treatment. Heart perforation with a defibrillator electrode is a rare but dangerous complication, which may lead to pacing failure, cardiac tamponade, cardiogenic shock, and even death. Even with a benign clinical course, one must think of cardiac wall perforation at any time after device implantation, and a contrast enhanced computer tomography (CTA) must be performed if perforation is suspected. At re-implantation, the lead should be located at a different anatomical position within the RV, preferably at the interventricular septal site, and manipulation of the injury site within the RV avoided.

Time Course of Electrical Remodeling of Native Conduction After Cardiac Resynchronization Therapy and Its Impact on Clinical Outcome.

BACKGROUND: Cardiac resynchronization therapy (CRT) induces structural and electrical remodeling (ER) in heart failure (HF) patients. Our aim was to assess time course of ER of native conduction and mechanical remodeling after CRT and impact of CRT-induced ER on clinical outcome. METHODS AND RESULTS: We prospectively included 62 patients (aged 66 ± 10 years). Echocardiographic and ECG parameters were measured at baseline and 1, 3, 6, 9, and 12 months after implantation. Biventricular pacing was temporary inhibited during each follow-up to record intrinsic ECG. ER was defined as a decrease in native pre-implantation QRS duration ≥10 ms. During follow-up HF hospitalizations, cardiovascular death and transplantation (combined end point) were recorded. There were significant changes in intrinsic ECG parameters during follow-up; the narrowing of QRS duration was already observed after 1 month (median 185 ms [interquartile range (IQR) 175-194] vs 180 ms [170-194]; P < .001). Left ventricular (LV) volumes decreased only after 3 months of CRT (median end-systolic volume 167 mL [137-206] vs 140 mL [112-196]; P < .001). Only patients with ER (n = 24) exhibited significant mechanical remodeling and showed superior survival free from the combined end point compared with patients without ER (log-rank P = .028). CONCLUSIONS: Electrical remodeling of native conduction precedes detectable left ventricular structural changes after CRT. ER of native conduction is associated with better clinical outcome following CRT.

Electrocardiographic parameters predict super-response in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients. However, determinants of response to CRT remain elusive. The aim of the study was to assess the value of ECG parameters to predict super-response in CRT patients. METHODS: A 12-lead surface ECG was recorded at baseline and immediately after CRT-device implantation. Baseline ECG parameters (QRS duration, bundle branch morphology, axis, PR interval, QTc, intrinsicoid deflection) and post-implant paced QRS duration were analyzed; relative change in QRS duration was calculated. Decrease of left ventricular end-systolic volume ≥30% after 12 months was classified as super-response. RESULTS: In group of 101 patients, 32 (31.7%) were super-responders. There were no significant differences in baseline ECG parameters between super-responders and other patients. Post-implant QRS duration was shorter in super-responders (148 ± 22 ms vs. 162 ± 28 ms; P=0.010). Only in super-responders was significant QRS reduction observed after implantation. Relative QRS shortening was higher in super-responders (12.1% (6.8 to 22.2) vs. 1.7% (-11.9 to 11.8); P=0.005). In a multivariable analysis post-implant QRS duration and relative QRS shortening remained independent predictor of super-response. CONCLUSION: Absolute post-implant QRS duration and relative QRS shortening are the only ECG parameters associated with super-response in CRT. Further prospective studies on larger population are warranted to determine our findings.

Impact of myocardial viability assessed by myocardial perfusion imaging on ventricular tachyarrhythmias in cardiac resynchronization therapy.

BACKGROUND: The presence of myocardial fibrosis is associated with ventricular tachyarrhythmia (VT) occurrence irrespective of cardiomyopathy etiology. The aim of our study was to evaluate the impact of global and regional viability on VTs in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Fifty-seven patients with advanced heart failure (age 62.3 ± 10.2; 38 men; 24 ischemic etiology) were evaluated using single-photon emission computed tomography myocardial perfusion imaging before CRT defibrillator device implantation. Global myocardial viability was determined by the number of viable segments in a 20-segment model. Regional viability was calculated as the mean tracer activity in the corresponding segments at left ventricular (LV) lead position. LV lead segments were determined at implant venography using 2 projections (left anterior oblique 30 and right anterior oblique 30) of coronary sinus tributaries. Patients were followed 30 (24-34) months for the occurrence of VTs. RESULTS: VTs were registered in 18 patients (31.6%). Patients without VTs had significantly more viable segments (17.6 ± 2.35 vs 14.2 ± 4.0; P = .002) and higher regional myocardial viability at LV lead position (66.1% ± 10.3% vs 54.8% ± 11.4% of tracer activity; P = .001) than those with VTs. In multivariate logistic regression models, the number of viable segments (OR = 0.66; 95% confidence interval (CI) 0.53-0.85; P = .001) and regional viability (OR = 0.90; 95% CI 0.85-0.97; P = .003) were the only independent predictors of VT occurrence. CONCLUSION: Global and regional myocardial viability are independently related to the occurrence of VTs in patients after CRT.

Association between frequent cardiac resynchronization therapy optimization and long-term clinical response: a post hoc analysis of the Clinical Evaluation on Advanced Resynchronization (CLEAR) pilot study.

AIMS: The long-term clinical value of the optimization of atrioventricular (AVD) and interventricular (VVD) delays in cardiac resynchronization therapy (CRT) remains controversial. We studied retrospectively the association between the frequency of AVD and VVD optimization and 1-year clinical outcomes in the 199 CRT patients who completed the Clinical Evaluation on Advanced Resynchronization study. METHODS AND RESULTS: From the 199 patients assigned to CRT-pacemaker (CRT-P) (New York Heart Association, NYHA, class III/IV, left ventricular ejection fraction <35%), two groups were retrospectively composed a posteriori on the basis of the frequency of their AVD and VVD optimization: Group 1 (n = 66) was composed of patients 'systematically' optimized at implant, at 3 and 6 months; Group 2 (n = 133) was composed of all other patients optimized 'non-systematically' (less than three times) during the 1 year study. The primary endpoint was a composite of all-cause mortality, heart failure-related hospitalization, NYHA functional class, and Quality of Life score, at 1 year. Systematic CRT optimization was associated with a higher percentage of improved patients based on the composite endpoint (85% in Group 1 vs. 61% in Group 2, P < 0.001), with fewer deaths (3% in Group 1 vs. 14% in Group 2, P = 0.014) and fewer hospitalizations (8% in Group 1 vs. 23% in Group 2, P = 0.007), at 1 year. CONCLUSION: These results further suggest that AVD and VVD frequent optimization (at implant, at 3 and 6 months) is associated with improved long-term clinical response in CRT-P patients.

Cardiac resynchronization therapy in a patient with amyloid cardiomyopathy.

Cardiac involvement in systemic light chain amyloidosis carries poor prognosis. Amyloid deposition in the myocardium can alter regional left ventricular contraction and cause dyssynchrony. Cardiac resynchronization therapy (CRT) is an effective treatment strategy for patients with advanced heart failure and echocardiographic dyssynchrony. We report a clinical and echocardiographic response of a patient with amyloid cardiomyopathy, treated with a combination of chemotherapy and CRT.

Effect of cardiac resynchronization therapy on beat-to-beat T-wave amplitude variability.

AIMS: T-wave amplitude variability (TAV) is a promising non-invasive predictor of arrhythmic events in patients with dilated cardiomyopathy. We aimed to evaluate the effect of cardiac resynchronization therapy (CRT) on native TAV, its relation with left ventricular (LV) reverse remodelling and the occurrence of ventricular tachyarrhythmias (VTs). METHODS AND RESULTS: In this prospective study, we included 40 heart failure patients with left bundle branch block in sinus rhythm (25 male; 16 with ischaemic aetiology; aged 62.7 ± 9.5 years; New York Heart Association class II-IV). Echocardiographic parameters and TAV were evaluated at baseline and 6 months after implantation of CRT device combined with an implantable cardioverter-defibrillator. T-wave amplitude variability was determined by a 20-min high-resolution electrocardiogram Holter recording during native conduction. After TAV assessment, patients were monitored for 15.7 ± 5.2 months for the occurrence of VTs. Decrease in median TAV [from 40.45 µV (24.75-56.00) to 28.15 µV (20.93-37.95), P = 0.004] was observed after 6 months of CRT. However, decrease of median TAV was only noticed in patients with LV reverse remodelling [46.9 µV (27.5-70.0) to 25.8 µV (20.2-32.4), P < 0.001] and in patients without VTs [40.5 µV (27.5-55.9) to 24.4 µV (17.1-31.5), P < 0.001]. Native median TAV > 35.4 µV after 6 months of CRT had an 83% sensitivity and 93% specificity for predicting the occurrence of VTs. CONCLUSIONS: Decrease of TAV after CRT is associated with LV reverse remodelling and indicates a reduction of the intrinsic arrhythmogenic substrate. Median TAV after CRT had a good predicting value for VT occurrence in long-term follow-up.

T-wave variability as a risk stratifier in patients with dilated cardiomyopathy.

BACKGROUND: T-wave alternans is an important identifier of patients at risk of sudden cardiac death (SCD), but the procedure usually requires stress testing. In this study, the variability of T-wave amplitude (TVAR) was evaluated at rest, as a risk stratifier for SCD. METHODS: This study included 57 patients in sinus rhythm and with a left ventricular ejection fraction < or =40%, of whom 34 (60%) received an implantable cardioverter-defibrillator (ICD) after surviving SCD, and 23 (40%) presented with ischemic or nonischemic cardiomyopathy and no history of SCD. A 20-minute high-resolution electrocardiographic recording for TVAR assessment was performed during supine rest. The vector magnitude was used as a primary lead for TVAR analysis. RESULTS: The mean, median, and maximum (max) values of TVAR were measured. The patients with ICD had a lower max TVAR than the patients without ICD (67 vs 95 muV; P = 0.045), though the mean and median TVAR values were similar. By multivariate logistic analysis, max TVAR remained a predictor of SCD, after adjustments for potentially confounding factors (P = 0.044). CONCLUSION: Max TVAR was a predictor of arrhythmic events in patients with dilated cardiomyopathy at rest.

Treatment of symptomatic coronary artery disease with stent implantation.

BACKGROUND: Percutaneous coronary intervention (PCI) with stent implantation is the therapy of choice for treatment of decreased blood flow through the coronary arteries. AIM: We evaluated the efficacy of the bare metal stent (BMS) for treatment of symptomatic coronary artery disease and compared BMS with the drug eluting stent (DES) to find out which one is better in the prevention of major adverse cardiac events (MACE) six months after stent implantation. MATERIALS AND METHODS: Our retrospective analysis included 387 consecutive patients with BMS implantation and 74 consecutive patients with DES implantation. Efficacy of BMS was evaluated by residual in-stent stenosis after the procedure. According to the Taxus II-Trial definition, MACE include cardiac death, acute myocardial infarction (AMI) and target vessel revascularization; the latter includes PCI with stent implantation or coronary artery bypass graft on previously revascularized vessel. RESULTS: In BMS group mean pre-procedure stenosis diameter was 81.9 ± 12.8% and mean post-procedure stenosis was 4.8% ± 12.5%. The residual in-stent stenosis was significantly higher in patients with longer lesions (p<0.05). Hypertension was the most frequent risk factor in both groups and AMI the commonest indication for stent implantation in the group with BMS, while stable and unstable angina pectoris in the group with DES, respectively. During the first six months after the implantation of DES, the incidence of MACE was significantly lower (p<0.05) compared to BMS. The most frequent subgroup of MACE present in the group with BMS was cardiac death, and in the group with DES it was repeated PCI with stent implantation. CONCLUSIONS: BMS provides and efficacious choice of treatment for patients with symptomatic coronary artery disease. Patients with longer lesions have higher residual in-stent stenosis after BMS implantation. Implantation of DES is more successful in preventing MACE in comparison with the implantation of BMS.

Repolarization heterogeneity in patients with cardiac resynchronization therapy and its relation to ventricular tachyarrhythmias.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to induce left ventricular reverse remodeling, but little is known about its influence on ventricular repolarization. OBJECTIVE: The purpose of this study was to evaluate changes in ventricular repolarization of native conduction after CRT and its relation to ventricular tachycardia (VT) and ventricular fibrillation (VF) during long-term follow-up. METHODS: We prospectively included 64 patients with heart failure treated with CRT. QT interval, TpTe, and TpTe/QT ratio were analyzed from 20-minute high-resolution ECGs that were recorded at baseline and 1, 3, 6, 9, and 12 months after CRT implantation. CRT was temporary inhibited during follow-up to record intrinsic ECG. Patients with a decrease of left ventricular end-systolic volume ≥15% at 12-month follow-up (mid-term follow-up) were considered as responders. Occurrences of VT/VF during follow-up were noted. RESULTS: Significant increase of repolarization heterogeneity in the first months after implantation was observed (P <.05) but then declined during 12 months of follow-up. Patients with VT/VF during long-term follow-up had higher repolarization heterogeneity at mid-term follow-up than patients without VT/VF (TpTe/QT ratio: 0.263 [0.204-0.278] vs 0.225 [0.204-0.239]; P = .045). Echocardiographic response at mid-term follow-up did not significantly influence the rate of VT/VF (log-rank P = .252). In multivariate Cox regression analysis, only high repolarization heterogeneity at mid-term follow-up (TpTe/QT ratio >0.260) was independently associated with high risk of VT/VF (hazard ratio 4.29; 95% confidence interval 1.40-13.15; P = .011). CONCLUSION: CRT induces time-dependent changes in repolarization parameters in the first year after implantation. High repolarization heterogeneity at mid-term follow-up was associated with higher rate of VT/VF during long-term follow-up.

The effect of long-term, low-dose tranexamic acid treatment on platelet dysfunction and haemoglobin levels in haemodialysis patients.

Some previous studies suggest that activation of the fibrinolytic system may induce platelet dysfunction in haemodialysis patients. Accordingly, inhibition of fibrinolysis may improve platelet dysfunction, and speculatively increase haemoglobin levels. We tested this hypothesis. The study group comprised 22 patients (14 male, 8 female, median age 62), who had been on maintenance haemodialysis for more than one year. Patients were treated for three months with low-dose tranexamic acid (TXA), a potent anti-fibrinolytic agent. The dosages of erythropoietin and the haemodialysis procedure were not changed significantly during the study. We primarily followed platelet function (by in vitro closure time test) and haemoglobin values. Patients were divided into those with substantially prolonged (N = 9) and those with slightly delayed or normal (N = 13) in vitro closure time. Treatment with TXA resulted in a significant improvement of platelet function and increased levels of haemoglobin in the first group, and no changes in either platelet function or haemoglobin values in the second group. TXA in the dosage used was biologically active, since a significant decrease in plasminogen and D-dimer were found in both groups. No significant changes in other fibrinolytic parameters or von Willebrand factor were found. No complications in terms of arterial or venous thrombosis were observed. Our pilot study suggests that long-term, low-dose TXA treatment of haemodialysis patients with substantially prolonged in vitro closure time results in a significant improvement of platelet dysfunction and a significant increase in haemoglobin values. These new, promising results merit further investigation in larger studies.

Intrathoracic impedance monitor alarm in a patient with cardiac resynchronisation therapy and advanced lung carcinoma.

The intrathoracic impedance monitor system measures impedance between the device case and the right ventricular coil and reflects intrathoracic fluid status. It is used to detect early volume overload in patients with chronic heart failure. We report a case of inappropriate activation of the intrathoracic impedance monitor alarm in a patient with epidermoid lung cancer and pleural carcinosis.

Inflammation markers in patients with coronary artery disease--comparison of intracoronary and systemic levels.

BACKGROUND AND AIM: Raised levels of inflammation markers are associated with worse prognosis in patients with coronary artery disease. It is generally believed, although it has never been proven, that inflammation markers are released from (un)stable plaques in coronary arteries. We investigated this issue by directly comparing levels of inflammation markers in coronary and systemic blood. PATIENTS AND METHODS: Patients with acute coronary syndrome (N = 11), stable angina pectoris (N = 10) and controls with noncoronary origin of chest pain (N = 9) were included in the study. Intracoronary blood samples were taken at the culprit lesion in the coronary artery in patients with acute coronary syndrome and from any coronary artery in the other two groups, together with systemic blood samples from the femoral vein and artery. Levels of high-sensitivity C reactive protein (hsCRP), interleukin 6, interleukin 8, interleukin 10, soluble receptor for interleukin 2 (tR IL-2) and myeloperoxidase were measured in all samples. RESULTS: We found significantly elevated levels of hsCRP and interleukin 10 in patients with acute coronary syndrome compared with patients with stable angina and the control patients. Notably, we did not find any difference between intracoronary and systemic levels of any inflammatory marker in patients with acute coronary syndrome. Furthermore, no difference between intracoronary and systemic levels of markers was present in patients with stable angina or in the control group. CONCLUSIONS: We observed that excess circulating inflammation markers, being characteristic of unstable coronary artery disease, are released from noncoronary sources. Thus, it may be speculated that systemic inflammation precedes local inflammation at the plaques, thereby transforming coronary disease from a stable to an unstable form.

G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease.

AIM: Granulocyte colony stimulating factor (G-CSF) therapy has been reported to be proarrhythmic. The in vivo mobilization of endothelial progenitor cells (EPCs) and the possible proarrhythmic effects in patients with severe coronary artery disease (CAD) and inducible ischemia have not been described. METHODS: We treated 8 patients (mean age = 69 +/- 10) suffering from severe CAD and angina pectoris (CCS 3 +/- 0.5) despite optimal medical therapy with subcutaneous G-CSF over 7 days to mobilize EPCs (CD34(+), CD117(+)). ECG monitoring was performed throughout the treatment period. A 24-hour ECG was recorded before and after G-CSF application. Mobilization of EPCs was monitored by fluorescent activated cell sorter (FACS-Calibur, Becton-Dickinson, Franklin Lakes, NJ, USA) analysis. Other medications remained unchanged. RESULTS: G-CSF therapy significantly increased peripheral leukocyte count from 7.45 +/- 2.4 to a peak of 42.2 +/- 10.9 x 10(3)/muL with a parallel rise in CD34(+) EPCs from 4.35 +/- 1.94 to 33.0 +/- 22.8/muL. The percentage of CD34(+)/CD117(+) cells changed from 0.32 +/- 0.25 to 0.24 +/- 0.28% (day of discharge, P = ns). During continuous ECG monitoring, no significant bradycardia, tachycardia, or changes in conduction were observed. Holter data collected after 7 days of G-CSF therapy showed no significant differences from baseline. A linear correlation (r = 0.76) was observed for the absolute values of deltaP wave duration and deltaCD34(+) concentration on day 2 compared to follow-up at 142 +/- 33 days, though it did not reach statistical significance (P = 0.29). CONCLUSION: This is the first study showing that mobilization of CD34(+) EPCs is safe in patients with severe CAD. The accompanying leukocytosis did not appear proarrhythmic. Changes in P wave duration might be attributable to G-CSF therapy.

Retrospective analysis of mode survival, reliability of atrial sensing and incidence of atrial tachyarrhythmias in 307 single-lead VDD pacemaker patients.

AIMS: The aim of this retrospective analysis was to investigate VDD mode survival, development of atrial tachyarrhythmias (AT), and long-term atrial sensing performance of VDD pacing systems. METHODS AND RESULTS: We implanted single-lead VDD pacemakers in patients with isolated atrioventricular block and performed a retrospective analysis of 307 patients who had their devices implanted between May 1994 and September 2001. In 39 patients (12.7%), the pacing mode had to be reprogrammed to a single-chamber ventricular pacing mode, mostly due to permanent AT. In 16 of these patients, the atrial sensing safety margin was less than 150%. The atrial sensing safety margin was insufficient, i.e. less than 100% in only seven patients. Although only 12 (3.9%) of the patients had a history of paroxysmal AT at the time of pacemaker implantation, 200 (65%) patients presented with AT during follow-up. The mean AT burden at the last follow-up was 2.5%. CONCLUSION: These data illustrate that single-lead VDD pacemakers can be applied without serious complications in a highly selected group of patients. Our main concern is the development of AT in a large part of our population. Over a 10-year period, two thirds of our patients presented with AT.

Effects of systolic atrial function on plasma renin activity and natriuretic peptide secretion after high rate atrial and ventricular pacing in dogs.

Rapid atrial rates cause electrical, structural remodeling, and neuro-humoral changes. This study compares the effects of mechanical remodeling on plasma renin activity (PRA) and atrial natriuretic peptide (ANP) secretion. Eight beagles were subjected to rapid atrial pacing (AP) at 400 beats/min for 16 days. After complete recovery of left ventricular function, they underwent rapid ventricular pacing (VP) at 240 beats/min of equal duration. Left atrial systolic maximal dimension (LAmax) and left atrial appendage (LAA) peak late emptying velocity (LAA-E) were assessed by echocardiography. Blood samples were taken from the right atrium and from the peripheral vein. LAmax after AP and VP enlarged significantly (2.16 +/- 0.21 cm vs 2.41 +/- 0.23 cm, P = 0.002). Compared with baseline, LAA-E velocities were significantly reduced (0.65 +/- 0.12 m/s vs 0.26 +/- 0.16 m/s, P = 0.001) after AP only. AP caused a significant elevation of PRA in right atrial (9.28 +/- 4.23 nmol/L per hour) and peripheral samples compared with baseline values (4.82 +/- 2.53 nmol/L per hour, P = 0.04). ANP levels increased after AP (1117.12 +/- 252.21 fmol/L) with respect to baseline values (824.37 +/- 159.08 fmol/L, P = 0.001). There was no difference in PRA and ANP levels between atrial and peripheral samples. Atrial size and impaired systolic appendage function play an important role in secretion of PRA and ANP. Both neuro-humoral pathways may be therapeutic targets in the treatment of patients with AF.

Impaired sinus node function and global atrial conduction time after high rate atrial pacing in dogs.

In animal and human studies, it has been shown that atrial fibrillation shortens the atrial refractory period and impairs its rate adaptation. The objective of this study was to evaluate the effects of high-rate pacing on sinus node function and intra-atrial conduction. Eight dogs were subjected to rapid atrial pacing (AP) at 400 bpm for 16 days. Sinus node recovery time (SNRT) and P-wave duration were measured at baseline, immediately after AP and four weeks after the termination of AP. SNRT immediately after AP was significantly prolonged at all pacing rates compared to the baseline values. P-wave duration was significantly longer after AP relative to the baseline values. All the variables were completely reversible four weeks after the termination of pacing. Rapid AP induces sinus node dysfunction and prolongs the intra-atrial conduction time. It is possible that the electrical remodelling extends to the sinus node as well.

Echocardiographic [correction of Ehocardiographic] evaluation of regional left atrial function after rapid atrial pacing.

Rapid regular atrial pacing (RAP) produces changes in atrial function similar to those caused by atrial fibrillation in animal models. Left atrial appendage (LAA) function represents regional atrial function. The aim of our study was to investigate the influence of RAP on left atrial regional function and to evaluate the reversibility of changes after termination of pacing in a canine model. Eight dogs were subjected to RAP (400 bpm) for 16 days. Transesophageal echocardiography was performed at baseline, immediately after RAP and 4 weeks after the termination of RAP. The LAA peak late emptying velocity (LAA-E) and filling wave (LAA-f) were measured. LAA-E velocities were significantly reduced and filling wave velocities (LAA-f) were significantly less negative after RAP compared with the baseline values. Four weeks after termination of pacing, the LAA-E and LAA-f velocities were normal. RAP results in impaired regional atrial systolic and diastolic function. The changes were completely reversible 4 weeks after termination of pacing. These results suggest that the LAA is mechanically stunned after RAP.