Not to Rush-Laboratory Parameters and Procedural Complications in Patients Undergoing Left Atrial Appendage Closure.

Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3−5) and the median HAS-BLED score was 3 (2−4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65−0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5−68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.

Machine learning-derived electrocardiographic algorithm for the detection of cardiac amyloidosis.

BACKGROUND: Diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited. OBJECTIVE: The aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis. METHODS: We applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool. FINDINGS: Areas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1-V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training. INTERPRETATION: Using a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.

Indications and Outcome in Patients Undergoing Left Atrial Appendage Closure-The Austrian LAAC Registry.

BACKGROUND: Complete real-world data on the indications and outcomes of left atrial appendage closure (LAAC) outside of clinical trials are rare. In this study, we stratified patients undergoing LAAC by indication groups. METHODS: This analysis of the national multicentre Austrian LAAC Registry comprised all patients that underwent LAAC up until 2018 at the currently active centres in Austria. The baseline characteristics, procedural details and outcomes between the following indication groups were compared: bleeding as an indication for LAAC ("bleeding" group) vs. thromboembolism despite oral anticoagulation (OAC; "thromboembolism" group) vs. an intolerance to OAC for reasons other than the above ("other" group). RESULTS: The analysis included 186 patients, with 59.7% in the "bleeding" group, 8.1% in the "thromboembolism" group and 32.2% in the "other" group. The CHADS2 score was the highest in the "thromboembolism" group and the HAS-BLED score was the highest in the "bleeding" group. The procedural outcomes were similar between groups (implantation success, 97.3%), with major complications occurring in 7.0% of patients. One-year survival free from stroke, bleeding or LAAC-associated hospitalisation was 83.9%, 90.0% and 81.4% in the "bleeding", "thromboembolism" and "other" groups, respectively (p = 0.891). CONCLUSIONS: In routine clinical practice, LAAC was used in a heterogeneous patient population with atrial fibrillation (AF) and contraindication, inefficacy or intolerance to OAC. The long-term outcome was favourable in all groups.

Open-Label Two-Dose Pilot Study of Landiolol for the Treatment of Atrial Fibrillation/Atrial Flutter in Caucasian Patients.

BACKGROUND: We investigated for the first time the suitability of landiolol, an ultra-short-acting ß1-specific ß-blocker, for the treatment of atrial fibrillation/atrial flutter (AF/AFL) in Caucasian patients.Methods and Results:The 20 study patients received landiolol as a continuous infusion (starting dose 40 µg/kg/min) with (B+CI) or without (CI) a preceding bolus dose (100 µg/kg/min administered over 1 min) in a prospective open-label study. The primary endpoint was the proportion of patients with sustained heart rate (HR) reduction ≥20% or to <90 beats/min within 16 min of starting the CI. Secondary endpoints were the pharmacodynamics, pharmacokinetics, AF/AFL symptoms, safety and tolerability of landiolol. At 16 min, HR was reduced in all patients treated with landiolol. The primary endpoint was met by 60% of patients in the CI group and 40% in the B+CI group without a significant group difference. Overall reduction of AF/AFL symptoms at 16 min was 72%. Safety and local tolerability of landiolol were excellent, and no serious adverse events occurred. CONCLUSIONS: Continuous infusion of landiolol with a starting dose of 40 µg/kg/min is suitable for the acute treatment of tachycardic AF/AFL in Caucasian patients. Administration of a preceding bolus seems unnecessary.

Noninvasive mapping before surgical ablation for persistent, long-standing atrial fibrillation.

OBJECTIVE: The study objective was to study the electrophysiologic mechanism of atrial fibrillation using a noninvasive, beat-by-beat, 3-dimensional mapping technique in patients with persistent and long-standing persistent atrial fibrillation undergoing concomitant surgical ablation. METHODS: In this pilot trial, 10 patients (6 male; mean age, 70 ± 10 years) with persistent atrial fibrillation were mapped preoperatively with a noninvasive surface system (ECVUE, CardioInsight, Medtronic Inc, Minneapolis, Minn). Eight patients were candidates for mitral valve surgery, 1 patient was a candidate for aortic valve and ascending aortic replacement, and 1 patient was a candidate for coronary bypass surgery. In 5 patients, tricuspid valve repair was also performed. The Cox-Maze III/IV was performed using combined cryoablation and bipolar radiofrequency, and the left appendage was removed in all cases. The median preprocedural duration of atrial fibrillation was 30 months, and the diameter of the left atrium was 63 mm. Atrial regions were divided according to the Bordeaux classification. RESULTS: Preoperative mapping was successful in all patients with clear identification of the potential mechanism of atrial fibrillation. Biatrial pathology was recognized in all subjects. Rotor and macro re-entry activity were present in all patients, whereas focal activity was demonstrated in only 6 patients. Rotor activity in the right atrium was documented in all patients. CONCLUSIONS: This is the first report on the preoperative use of the ECUVE in surgical candidates for concomitant surgical procedures. The fact that a biatrial mechanism for atrial fibrillation was detected in all patients emphasizes the importance of a Cox-Maze III/IV procedure to treat patients with valvular heart disease and nonparoxysmal atrial fibrillation. Preoperative mapping has the potential to significantly improve our understanding of the pathophysiology in atrial fibrillation and better guide the surgical ablation procedure of choice in a single patient.

Ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical presentation, risk stratification and results of long-term follow-up.

BACKGROUND: Not all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are at risk for sudden cardiac death. The aim of the study was to evaluate the risk stratification in patients with ARVD/C. METHODS AND RESULTS: Programmed ventricular stimulation (PVS) was performed in 34 ARVD/C patients. Twenty-two, 7 and 4 patients had documented sustained monomorphic ventricular tachycardia (smVT), non-smVT and ventricular fibrillation, respectively. One patient experienced syncope only. An implantable cardioverter defibrillator (ICD) was implanted in 11 patients inducible in smVT with hemodynamic compromise, in 4 patients with documented ventricular fibrillation and in one patient with non-smVT (194 ms tachycardia cycle length) (ICD group, n = 16). Ten patients were left without any antiarrhythmic therapy, 5 patients received antiarrhythmic drugs and 3 patients underwent successful VT ablation (non-ICD group, n = 18). Thirteen patients had an abnormal signal averaged ECG. During 6.5 +/- 2.4 years 69% of ICD patients received appropriate discharges and one non-ICD patient had a hemodynamically tolerated smVT recurrence (no sudden cardiac death in both groups). Comparison between the cycle lengths of clinical VT, induced VT and follow-up VT revealed a strong relationship (R = 0.62-0.88). On multivariate analysis abnormal signal averaged ECG and decreased left ventricular ejection fraction were statistically significant predictors for VT recurrence. CONCLUSIONS: In ARVD/C the tachycardia cycle length of clinical VT, PVS-induced VT and follow-up VT correlate well implicating that a PVS-guided approach does not provide additional information. Spontaneous arrhythmia in combination with clinical presentation allows identification of patients in need for an ICD.

First human chronic experience with cardiac contractility modulation by nonexcitatory electrical currents for treating systolic heart failure: mid-term safety and efficacy results from a multicenter study.

INTRODUCTION: Conventional electrical therapies for heart failure (HF) encompass defibrillation and ventricular resynchronization for patients at high risk for lethal arrhythmias and/or with inhomogeneous ventricular contraction. Cardiac contractility modulation (CCM) by means of nonexcitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. The aim of this multicenter study was to assess the chronic safety and preliminary efficacy of an implantable device delivering this novel form of electrical therapy. METHODS AND RESULTS: Thirteen patients with drug-resistant HF (New York Heart Association [NYHA] class III) were consecutively implanted with a device (OPTIMIZER II) delivering CCM biphasic square-wave pulses (20 ms, 5.8-7.7 V, 30 ms after detection of local activation) through two right ventricular leads screwed into the right aspect of the interventricular septum. CCM signals were delivered 3 hours daily over 8 weeks (3-hour phase) and 7 hours daily over the next 24 weeks (7-hour phase). Safety and feasibility of this novel therapy were regarded as primary endpoints. Preliminary clinical efficacy, -as expressed by changes in ejection fraction (EF), NYHA class, 6-minute walking test (6-MWT), peak O(2) uptake (peak VO(2)), and Minnesota Living with HF Questionnaire (MLWHFQ), was assessed at baseline and at the end of each phase. At the end of follow-up (8.8 +/- 0.2 months), all patients were alive, without heart transplantation or need for left ventricular assist device. Serial 24-hour Holter analysis revealed no proarrhythmic effect. No devices malfunctioned or failed for any reason other than end-of-battery life. Throughout the two study phases, EF improved from 22.7 +/- 7% to 28.7 +/- 7% and 37 +/- 13% (P = 0.004), 6-MWT from 418 +/- 99 m to 477 +/- 96 m and 510 +/- 107 m (P = 0.002), MLWHFQ from 36 +/- 21 to 18 +/- 12 and 7 +/- 6 (P = 0.002), peak VO(2) from 13.7 +/- 1.1 to 14.9 +/- 1.9 to 16.2 +/- 2.4 (P = 0.037), and NYHA class from 3 to 1.8 +/- 0.4 to 1.5 +/- 0.7 (P < 0.001). CONCLUSION: CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms, and functional status. CCM therapy for 7 hours per day is associated with greater dispersion near the mean, emphasizing the need to individually tailor CCM delivery duration. The technique appears to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.

Chronic electrical stimulation during the absolute refractory period of the myocardium improves severe heart failure.

AIM: In experimental studies, nonexcitatory electrical stimulation delivered at the time of absolute myocardial refractoriness resulted in cardiac contractility modulation (CCM) with improved systolic function. This study reports the initial experience with CCM in patients with chronic heart failure. METHODS AND RESULTS: Twenty-five patients, 23 males, with a mean age of 62+/-9 years and drug-refractory NYHA class III heart failure were assigned to CCM-generator implantation. The underlying heart disease was idiopathic dilated cardiomyopathy in 12 patients and coronary heart disease in 13 patients. Acute efficacy of CCM with 7.73-V stimuli delivered via two right ventricular leads was evaluated by measuring the time derivative of left ventricular pressure (dP/dt). After implantation, the CCM generator was activated for 3 h daily over 8 weeks. In 23/25 patients the CCM system was implanted successfully. Heart failure significantly improved from NYHA class III to class II in 15 patients and to class I in 4 patients (p < 0.000001), left ventricular ejection fraction improved from 22+/-7% to 28+/-8% (p = 0.0002), and the Minnesota Living with Heart Failure Score improved from 43+/-22 to 25+/-18 (p = 0.001). The 6-min walk test increased from 411+/-86 to 465+/-81 m (p= 0.02). Nine patients (39%) had intermittent sensations associated with CCM delivery. There were two (8%) non-device-related deaths during follow-up. CONCLUSIONS: These preliminary data indicate that CCM by delivery of intermittent nonexcitatory electrical stimuli is a promising technique for improving ventricular systolic function and symptoms in patients with drug-refractory NYHA class III heart failure.