Echocardiographic and Electrocardiographic Determinants of Atrial Cardiomyopathy Identify Patients with Atrial Fibrillation at Risk for Left Atrial Thrombogenesis.

Objective: Atrial cardiomyopathy (ACM) is associated with development of AF, left atrial (LA) thrombogenesis, and stroke. Diagnosis of ACM is feasible using both echocardiographic LA strain imaging and measurement of the amplified p-wave duration (APWD) in digital 12-lead-ECG. We sought to determine the thresholds of LA global longitudinal strain (LA-GLS) and APWD that identify patients with AF at risk for LA appendage (LAA) thrombogenesis. Methods: One hundred and twenty-eight patients with a history of AF were included. Left atrial appendage maximal flow velocity (LAA-Vel, in TEE), LA-GLS (TTE), and APWD (digital 12-lead-ECG) were measured in all patients. ROC analysis was performed for each method to determine the thresholds for LA-GLS and the APWD, enabling diagnosis of patients with LAA-thrombus. Results: Significant differences in LA-GLS were found during both rhythms (SR and AF) between the thrombus group and control group: LA-GLS in SR: 14.3 ± 7.4% vs. 24.6 ± 9.0%, p < 0.001 and in AF: 11.4 ± 4.2% vs. 16.1 ± 5.0%, p = 0.045. ROC analysis revealed a threshold of 17.45% for the entire cohort (AUC 0.82, sensitivity: 84.6%, specificity: 63.6%, Negative Predictive Value (NPV): 94.3%) with additional rhythm-specific thresholds: 19.1% in SR and 13.9% in AF, and a threshold of 165 ms for APWD (AUC 0.90, sensitivity: 88.5%, specificity: 75.5%, NPV: 96.2%) as optimal discriminators of LAA-thrombus. Moreover, both LA-GLS and APWD correlated well with the established contractile LA-parameter LAA-Vel in TEE (r = 0.39, p < 0.001 and r = −0.39, p < 0.001, respectively). Conclusion: LA-GLS and APWD are valuable diagnostic predictors of left atrial thrombogenesis in patients with AF.

Electrocardiographic diagnosis of atrial cardiomyopathy to predict atrial contractile dysfunction, thrombogenesis and adverse cardiovascular outcomes.

Thromboembolism and stroke are dreaded complications in atrial fibrillation (AF). Established risk stratification models identify susceptible patients, but their discriminative properties are poor. Atrial cardiomyopathy (ACM) is associated to thromboembolism and stroke in smaller studies, but the modalities used for ACM-diagnosis (MRI and endocardial mapping) are unsuitable for widespread population screening. We aimed to investigate an ECG-based diagnosis of ACM using amplified p-wave analysis (APWA) for stratification of thromboembolic risk and cardiovascular outcome. In this case-control study, ACM-staging was performed using APWA on digital 12-lead sinus rhythm-ECGs in patients with LAA-thrombus and a propensity-score-matched control-cohort. Left atrial contractile function and thrombi were evaluated by transesophageal echocardiography (TEE). Outcome for MACCE including death was assessed using official registries and structured phone interviews. Left-atrial appendage [LAA]-thrombi and appropriate sinus rhythm-ECGs for ACM-staging were found in 109 of 4086 patients that were matched 1:1 to control patients without thrombus (218 patients in total). Both cohorts were comparable regarding cardiovascular risk factors, anticoagulants and CHA2DS2-VASC-score. ACM-stages 1 to 3 (equivalent to no, moderate and extensive ACM) were found in 63 (57.8%), 36 (33.0%) and 10 (9.2%) of patients without and 3 (2.8%), 23 (21.1%) and 83 (76.1%) of patients with LAA-thrombi. Atrial contractile function decreased from ACM-stages 1 to 3 (LAA-flow velocities 38 ± 16 cm/s, 31 ± 15 cm/s and 21 ± 12 cm/s; p < 0.0001), while the likelihood for LAA-thrombus increased (2.8%, 21.1% and 76.1%, p < 0.001). Multivariable analysis confirmed an independent odds ratio for LAA-thrombus of 24.6 (p < 0.001) per ACM-stage. Two-year survival free of stroke/TIA, hospitalization for heart failure, myocardial infarction or all-cause death was strongly reduced in ACM-stage 3 (53.8%) compared to no or moderate ACM (82.8% and 84.7%, respectively; p < 0.0001). Electrocardiographic diagnosis of ACM identifies patients with atrial contractile dysfunction and atrial thrombi at risk for adverse cardiovascular outcomes and death.

Specific Electrogram Characteristics Identify the Extra-Pulmonary Vein Arrhythmogenic Sources of Persistent Atrial Fibrillation - Characterization of the Arrhythmogenic Electrogram Patterns During Atrial Fibrillation and Sinus Rhythm.

Identification of atrial sites that perpetuate atrial fibrillation (AF), and ablation thereof terminates AF, is challenging. We hypothesized that specific electrogram (EGM) characteristics identify AF-termination sites (AFTS). Twenty-one patients in whom low-voltage-guided ablation after pulmonary vein isolation terminated clinical persistent AF were included. Patients were included if short RF-delivery for <8sec at a given atrial site was associated with acute termination of clinical persistent AF. EGM-characteristics at 21 AFTS, 105 targeted sites without termination and 105 non-targeted control sites were analyzed. Alteration of EGM-characteristics by local fibrosis was evaluated in a three-dimensional high resolution (100 µm)-computational AF model. AFTS demonstrated lower EGM-voltage, higher EGM-cycle-length-coverage, shorter AF-cycle-length and higher pattern consistency than control sites (0.49 ± 0.39 mV vs. 0.83 ± 0.76 mV, p < 0.0001; 79 ± 16% vs. 59 ± 22%, p = 0.0022; 173 ± 49 ms vs. 198 ± 34 ms, p = 0.047; 80% vs. 30%, p < 0.01). Among targeted sites, AFTS had higher EGM-cycle-length coverage, shorter local AF-cycle-length and higher pattern consistency than targeted sites without AF-termination (79 ± 16% vs. 63 ± 23%, p = 0.02; 173 ± 49 ms vs. 210 ± 44 ms, p = 0.002; 80% vs. 40%, p = 0.01). Low voltage (0.52 ± 0.3 mV) fractionated EGMs (79 ± 24 ms) with delayed components in sinus rhythm ('atrial late potentials', respectively 'ALP') were observed at 71% of AFTS. EGMs recorded from fibrotic areas in computational models demonstrated comparable EGM-characteristics both in simulated AF and sinus rhythm. AFTS may therefore be identified by locally consistent, fractionated low-voltage EGMs with high cycle-length-coverage and rapid activity in AF, with low-voltage, fractionated EGMs with delayed components/ 'atrial late potentials' (ALP) persisting in sinus rhythm.

Amplified P-wave duration predicts new-onset atrial fibrillation in patients with heart failure with preserved ejection fraction.

BACKGROUND: Atrial fibrillation (AF) increases morbidity and mortality in heart failure with preserved ejection fraction (HFpEF), yet identification of HFpEF-patients at risk for new-onset AF is challenging. Amplified P-wave duration (APWD) non-invasively detects arrhythmogenic atrial substrate with high accuracy. We hypothesized that APWD may help in the prediction of new-onset AF in HFpEF. METHODS: Patients with suspected HFpEF (n = 99, left ventricular ejection fraction > 50%, no evidence of valvulopathy, coronary artery disease, or non-cardiac dyspnea) underwent exercise testing with concomitant right-heart catheterization. Normal resting pulmonary capillary wedge pressure (PCWP; < 12 mmHg) with an increase during exercise > 25.5 mmHg/W/kg defined early HFpEF. Advanced HFpEF was diagnosed with PCWP > 12 mmHg at rest. Arrhythmogenic atrial substrate (defined as APWD > 150 ms) was investigated on digitized standard 12-lead ECGs and patients were followed for new-onset AF at 6-month intervals. RESULTS: Forty-seven patients had normal exercise haemodynamics and served as controls. Early and advanced HFpEF was diagnosed in 29 and 23 patients, respectively. Eighty-seven per cent of patients with advanced HFpEF had evidence of arrhythmogenic atrial substrate, (APWD 175 ± 29 ms vs. 132 ± 14 ms in controls, p < 0.0001), which was associated with a tenfold increased risk for new-onset AF during 4.6 years of follow-up (hazard ratio [HR] 9.684, 95% CI 2.61-35.89, p < 0.0001). Early HFpEF was neither related to APWD (p = 0.395), nor to a higher risk for AF (HR 3.44, 95% CI 0.57-20.72, p = 0.178). Importantly, the presence of arrhythmogenic substrate was independent of left atrial indexed volume. CONCLUSION: The analysis of amplified P-wave duration (APWD) allows for the prediction of new-onset AF in patients with advanced HFpEF.

Amplified sinus-P-wave reveals localization and extent of left atrial low-voltage substrate: implications for arrhythmia freedom following pulmonary vein isolation.

AIMS: Presence of arrhythmogenic left atrial (LA) low-voltage substrate (LVS) is associated with reduced arthythmia freedom rates following pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF). We hypothesized that LA-LVS modifies amplified sinus-P-wave (APW) characteristics, enabling identification of patients at risk for arrhythmia recurrences following PVI. METHODS AND RESULTS: Ninety-five patients with persistent AF underwent high-density (>1200 sites) voltage mapping in sinus rhythm. Left atrial low-voltage substrate (<0.5 and <1.0 mV) was quantified in a 10-segment LA model. Amplified sinus-P-wave-morphology and -duration were evaluated using digitized 12-lead electrocardiograms (40-80 mm/mV, 100-200 mm/s). 12-months arrhythmia freedom following circumferential PVI was assessed in 139 patients with persistent AF. Left atrial low-voltage substrate was most frequently (84%) found at the anteroseptal LA. Characteristic changes of APW were related to the localization and extent of LA-LVS. At an early stage, LA-LVS predominantly located to the LA-anteroseptum and was associated with APW-prolongation (≥150 ms). More extensive LA-LVS involved larger areas of LA-anteroseptum, leading to morphological changes of APW (biphasic positive-negative P-waves in inferior leads). Severe LA-LVS involved the LA-anteroseptum, roof and posterior LA, but spared the inferior LA, lateral LA, and LA appendage. In this advanced stage, widespread LVS at the posterior LA abolished the negative portion of P-wave in the inferior leads. The delayed activation of the lateral LA and LA appendage produced the late positive deflections in the anterolateral leads, resulting in the "late-terminal P"-pattern. Structured analysis of APW-duration and -morphology stratified patients to their individual extent of LA-LVS (Grade 1: mean LA-LVS 4.9 cm2 at <1.0 mV; Grade 2: 28.6 cm2; Grade 3: 42.3 cm2; P < 0.01). The diagnostic value of APW-duration for identification of LA-LVS was significantly superior to standard P-wave-amplification (c-statistic 0.945 vs. 0.647). Arrhythmia freedom following PVI differed significantly between APW-predicted grades of LA-LVS-severity [hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.18-4.83; P = 0.015 for Grade 1 vs. Grade 2; HR 1.79, 95% CI 1.00-3.21, P = 0.049 for Grade 2 vs. Grade 3). Arrhythmia freedom 12 months after PVI was 77%, 53%, and 33% in Grades 1, 2 and 3, respectively. CONCLUSION: Localization and extent of LA-LVS modifies APW-morphology and -duration. Analysis of APW allows accurate prediction of LA-LVS and enables rapid and non-invasive estimation of arrhythmia freedom following PVI.

Rapid improvement in left ventricular function after sinus rhythm restoration in patients with idiopathic cardiomyopathy and atrial fibrillation.

AIMS: Sinus rhythm restoration (SRR) in patients with atrial fibrillation (AF) and heart failure may improve systolic function and impact on consecutive clinical management, but time course and potential predictors of response to SRR are uncertain. METHODS AND RESULTS: We prospectively studied 50 consecutive patients who presented in heart failure with reduced ejection fraction (EF) and concomitant AF. After exclusion of valvular and coronary artery disease patients underwent electrical cardioversion. Serial echocardiography, cardiac magnetic resonance imaging (cMRI), and 24-h electrocardiograms were performed at baseline, and on Days 3 and 40 following SRR. Baseline left ventricular EF of the study population (76% male, age 69 ± 11 years) was 30 ± 7%. Sustained SRR (≥3 days) significantly improved EF (Day 3: 43 ± 7%, n = 46; Day 40: 53 ± 9%, n = 34; P < 0.001) as quantified by echocardiography. Comparable results were obtained using cMRI (baseline: 29 ± 8%; Day 3: 42 ± 9%). Three patients showed no response to SRR (EF improvement <15%). The percentage of patients meeting current criteria for implantable cardioverter-defibrillator (ICD) implantation for primary prevention dropped from 76% (n = 38) to 11% (n = 3) on Day 40 following SRR. No specific clinical or echocardiographic factor predicting improved EF after SRR could be identified. CONCLUSION: The majority of patients presenting with non-ischaemic, non-valvular heart failure with reduced EF and concomitant AF show a significant and rapid improvement in EF following SRR. An attempt at SRR and reassessment of the need for ICD implantation after 40 days may be warranted in all such patients.

The Duration of the Amplified Sinus-P-Wave Identifies Presence of Left Atrial Low Voltage Substrate and Predicts Outcome After Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation.

OBJECTIVES: Left atrial (LA) low-voltage substrate (LVS) potentially slows intra-atrial conduction, which might identify patients at risk for arrhythmia recurrence following pulmonary vein isolation (PVI). BACKGROUND: Up to 50% of patients with persistent atrial fibrillation (AF) have arrhythmia recurrence following PVI, mostly due to arrhythmogenic LA LVS. METHODS: Seventy-two patients with persistent AF underwent electrocardioversion to sinus rhythm and high-density voltage mapping of the left atrium. Invasively measured LA activation time and P-wave duration (PWD; total PWD and LA PWD [measured from -dV/dt in leads V1 and V2 until the end of the P-wave]) on amplified (40 to 50 mm/mV, 100 to 200 mm/s) digitized 12-lead electrocardiography (ECG) were compared with the extent of LA LVS (<0.5 and <1. 0mV). Freedom from arrhythmia following PVI was evaluated in 143 patients with persistent AF stratified according to amplified PWD before ablation. RESULTS: LA LVS resulted in regional conduction delay, which increased LA activation time (r = 0.79). LA PWD strongly correlated with LA activation time (r = 0.96) and LA LVS (r = 0.80). As the first (right atrial) portion of the P-wave (from P-wave beginning until -dV/dt in leads V1 and V2) was not affected by LA LVS, total PWD correlated with LA LVS (r = 0.84). PWD ≥150 ms identified advanced LA LVS with 94.3% sensitivity and 91.7% specificity. One-year arrhythmia freedom following PVI-only was significantly higher in patients with PWD <150 ms (n = 73) compared with those with prolonged PWD ≥150 ms (n = 70) (72.0% vs. 40.8%; p = 0.003). CONCLUSIONS: Advanced arrhythmogenic LVS is associated with significant intra-atrial conduction delay, which is accurately measurable by prolongation of PWD on amplified 12-lead ECG. PWD ≥150 ms during sinus rhythm measured prior to ablation identifies patients with persistent AF who are at increased risk for arrhythmia recurrence following PVI.

Transseptal access for left atrial ablation: the catheter-probing techniques are not without risk.

BACKGROUND: Transseptal puncture (TP) is a prerequisite for LA ablations. LA access can be gained by catheter probing in case of PFO (trans-PFO method) or puncture of the interatrial septum (IAS) using a transseptal needle. A 2nd access can again be gained via PFO, a 2nd TP or catheter probing of the previous puncture site (probe-TS method). This study investigates the risk factors and complications related to the mode of transseptal access. METHODS AND RESULTS: From August 2010 to August 2012, a total of 544 LA ablations, were performed. The mode of LA access was either a double TP or a single TP followed by the probe-TS or the trans-PFO method, respectively. TP was always guided by TEE and was successfully performed without complications in all cases. In contrast, 6/410 patients (1.5%) in whom catheter probing was performed (probe-TS, n = 4, trans-PFO, n = 2) had a dissection of the superior IAS originating from inside the oval fossa (n = 5) or perforation above the oval fossa (n = 1). Perforation into the pericardial space occurred in 4/6 patients, leading to one cardiac tamponade. In 5/6 patients, LA ablation was successfully completed, after repeated TP, despite effective anticoagulation. Patients with complications had the following characteristics: LA size 46 ± 4 mm, persistent AF (5/6), a repeat transseptal procedure (3/6) and a right-sided pouch (RSP, 5/6). CONCLUSIONS: Interatrial septum dissection/perforation, occasionally with perforation into the pericardial space, is an unreported complication of TP, especially with the catheter-probing techniques. An RSP is an unrecognized risk factor in this context and can be visualized by TEE.

"Dormant transisthmus conduction" revealed by adenosine after cavotricuspid isthmus ablation.

BACKGROUND: Linear radiofrequency ablation at the cavotricuspid isthmus (CTI) is the treatment of choice for typical flutter. Despite a high acute success rate, reconduction through the CTI may occur in approximately 15% of patients and eventually lead to flutter recurrence. OBJECTIVE: The purpose of this study was to test the hypothesis that injection of adenosine may reveal transient CTI reconduction and predict early relapse of permanent CTI conduction. METHODS: Thirty-one patients with CTI-dependent flutter (mean age 65 ± 11 years, 87% male, ejection fraction 55% ± 11%) were included in the study. CTI ablation was performed using an open-irrigated ablation catheter. Bidirectional conduction block was confirmed using conventional criteria. Subsequently, transisthmus conduction was reevaluated after adenosine injection. During a 30-minute waiting period, permanent recovery of CTI conduction was monitored. During a mean follow-up of 6 ± 3 months, clinical recurrences of typical flutter were assessed. RESULTS: Bidirectional isthmus block was achieved in all patients. Injection of 16 ± 3 mg adenosine IV induced transient second- or third-degree AV block in all patients. An adenosine-induced brief sequence reversal at the right lateral wall occurred in 6 of 31 patients (19%) and revealed transient CTI reconduction. Among these 6 patients, 4 (67%) had permanent recovery of transisthmus conduction in the subsequent waiting period; the remaining 2 patients (33%) had clinical recurrence of common flutter. Importantly, no patient without adenosine-mediated dormant transisthmus conduction (25/31 [81%]) showed permanent recovery during the waiting period or clinical flutter recurrence during follow-up. CONCLUSION: Adenosine-induced "dormant transisthmus conduction" precedes early relapse of permanent CTI conduction. Patients without "dormant transisthmus conduction" develop no recovery of conduction during the postablation waiting period. Routine use of adenosine for assessment of ablation lines may help to reduce the clinical recurrence of the underlying arrhythmia.

[An unusual cause of recurrent chest pain in a highly trained recreational athlete]. / Ungewöhnliche Ursache rezidivierender AP-Beschwerden bei einem Ausdauersportler.

ANAMNESIS: Here, the case of a 48-year-old highly trained patient without classic myocardial risk factors is described who reported on frequent and recurrent angina pectoris. In a previous examination, the test for cardiac troponin T (cTnT) was slightly positive, however, cardiac examination including myocardial perfusion scintigraphy and coronary catheterization was without pathologic findings. Worth mentioning in the past medical history was a rheumatoid arthritis with persistent Raynaud's symptoms and hemoglobin as well as hematocrit levels in the upper normal range. EXAMINATIONS AND COURSE OF EVENTS: The patient reported that symptoms would occur most likely during long-term endurance exercise. Therefore, a bicycle ergometry with 180 W and open ending was performed. After 1.55 h, the patient complained of severe angina pectoris. The ECG showed massive ST segment elevations in II, III, and aVF (Figure 2). However, coronary catheterization showed no major stenosis or occlusion. Nevertheless, cTnT increased to 0.979 ng/ml. (Therefore, the reason for the symptomatic ST elevation was believed to be a myocardial tissue damage due to coronary vasospasm and the patient received an antivasospastic medication (amlodipine, atorvastatin, and acetylsalicylic acid [ASS]). After 6 months, the patient had a relapse during moderate physical activity. The ECG showed an ST segment depression in V(4) and V(5) while markers for myocardial tissue damage including cTnT were negative. A coronary CT angiography was performed that revealed a subtotal stenosis of the proximal LAD (Fig ure 3), which was successfully treated by angioplasty with subsequent stenting. In the course of further examinations, a polycythemia vera (JAK2-V617 mutation) was diagnosed as the cause for the high hemoglobin and hematocrit levels. Since then, the patient was without further events under a medication consisting of ASS, atorvastatin, candesartan, and intermittent phlebotomy. CONCLUSION: Although a relative weighting is difficult, it can be assumed that the combined effects of a polycythemia- associated hypercoagulability, an increased reagibility of the coronary arteries (aggravated by physical stress) as well as a hemoconcentration following prolonged exercise, could account for symptomatic recurrent minor thrombotic coronary events as well as the subtotal occlusion of the LAD. Obviously, this could not be prevented by a healthy lifestyle, regular physical activity, and the absence of classic coronary risk factors.