Pulsed Field Ablation of Atrial Fibrillation: An Initial Australian Single-Centre Experience.

BACKGROUND: Pulsed field ablation (PFA) is a newer ablation energy source with the potential to reduce complications and improve efficacy compared to conventional thermal atrial fibrillation (AF) ablation. This study aimed to present an initial single-centre Australian experience of PFA for AF ablation. METHODS: Initial consecutive patients undergoing PFA for paroxysmal or persistent AF at a single centre were included. Baseline patient characteristics, procedural data and clinical outcomes were collected prospectively at the time of the procedure. Patients were followed up at 3 months and 6-monthly thereafter. RESULTS: In total, 100 PFA procedures were performed in 97 patients under general anaesthesia. All pulmonary veins (403 of 403) were successfully isolated acutely. Median follow-up was 218 days (range, 16-343 days), and the Kaplan-Meier estimate for freedom from atrial arrhythmias at 180 days was 87% (95% confidence interval 79%-95%). Median procedure time was 74 minutes (range, 48-134 minutes). Median fluoroscopy dose-area product was 345 µGym2 (interquartile range, 169-685 µGym2). Two (2%) pseudoaneurysm vascular access complications occurred. There were no cases of thromboembolic complications, stroke, phrenic nerve palsy, pulmonary vein stenosis, atrio-oesophageal fistula, or pericardial tamponade. CONCLUSIONS: Pulsed field ablation can be performed safely and efficiently, with encouraging efficacy in early follow-up. Further data and clinical trials will be required to assess the comparative utility of PFA in contemporary AF ablation practice.

Genetic mechanisms underlying arrhythmogenic mitral valve prolapse: Current and future perspectives.

Mitral valve prolapse (MVP) is a heart valve disease that is often familial, affecting 2%-3% of the general population. MVP with or without mitral regurgitation can be associated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). Research on familial MVP has specifically focused on genetic factors, which may explain the heritable component of the disease estimated to be present in 20%-35%. Furthermore, the structural and electrophysiological substrates underlying SCD/ventricular arrhythmia risk in MVP have been studied postmortem and in the electrophysiology laboratory, respectively. Understanding how familial MVP and rhythm disorders are related may help patients with MVP by individualizing risk and working to develop effective management strategies. This contemporary, state-of-the-art, expert review focuses on genetic factors and familial components that underlie MVP and arrhythmia and encapsulates clinical, genetic, and electrophysiological issues that should be the objectives of future research.

Freedom from atrial arrhythmia and other clinical outcomes at 5 years and beyond after catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

AIMS: Catheter ablation of atrial fibrillation (AF) is now a mainstream procedure although long-term outcomes are uncertain. We performed a systematic review and meta-analysis of procedural outcomes at 5 years and beyond. METHODS AND RESULTS: We searched PubMed and Embase and after the screening, identified 73 studies (67 159 patients) reporting freedom from atrial arrhythmia, all-cause death, stroke, and major bleeding at ≥5 years after AF ablation. The pooled mean age was 59.7y, 71.5% male, 62.2% paroxysmal AF, and radiofrequency was used in 78.1% of studies. Pooled incidence of freedom from atrial arrhythmia at 5 years was 50.6% (95%CI 45.5-55.7%) after a single ablation and 69.7% [95%CI (confidence interval) 63.8-75.3%) after multiple procedures. The incidence was higher among patients with paroxysmal compared with non-paroxysmal AF after single (59.7% vs. 33.3%, p = 0.002) and multiple (80.8% vs. 60.6%, p < 0.001) ablations but was comparable between radiofrequency and cryoablation. Pooled incidences of other outcomes were 6.0% (95%CI 3.2-9.7%) for death, 2.4% (95%CI 1.4-3.7%) for stroke, and 1.2% (95%CI 0.8-2.0%) for major bleeding at 5 years. Beyond 5 years, freedom from arrhythmia recurrence remained largely stable (52.3% and 64.7% after single and multiple procedures at 10 years), while the risk of stroke and bleeding increased over time. CONCLUSION: Nearly 70% of patients having multiple ablations remained free from atrial arrhythmia at 5 years, with the incidence slightly decreasing beyond this period. Risk of death, stroke, and major bleeding at 5 years were low but increased over time, emphasizing the importance of long-term thromboembolism prevention and bleeding risk management.

Catheter Ablation vs Antiarrhythmic Drug Therapy for Treatment of Premature Ventricular Complexes: A Systematic Review.

There is variability in treatment modalities for premature ventricular complexes (PVCs), including use of antiarrhythmic drug (AAD) therapy or catheter ablation (CA). This study reviewed evidence comparing CA vs AADs for the treatment of PVCs. A systematic review was performed from the Medline, Embase, and Cochrane Library databases, as well as the Australian and New Zealand Clinical Trials Registry, U.S. National Library of Medicine ClinicalTrials database, and the European Union Clinical Trials Register. Five studies (1 randomized controlled trial) enrolling 1,113 patients (57.9% female) were analyzed. Four of five studies recruited mainly patients with outflow tract PVCs. There was significant heterogeneity in AAD choice. Electroanatomic mapping was used in 3 of 5 studies. No studies documented intracardiac echocardiography or contact force-sensing catheter use. Acute procedural endpoints varied (2 of 5 targeted elimination of all PVCs). All studies had significant potential for bias. CA seemed superior to AADs for PVC recurrence, frequency, and burden. One study reported long-term symptoms (CA superior). Quality of life or cost-effectiveness was not reported. Complication and adverse event rates were 0% to 5.6% for CA and 9.5% to 21% for AADs. Future randomized controlled trials will assess CA vs AADs for patients with PVCs without structural heart disease (ECTOPIA [Elimination of Ventricular Premature Beats with Catheter Ablation versus Optimal Antiarrhythmic Drug Treatment]), with impaired LVEF (PAPS [Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy] Pilot), and with structural heart disease (CAT-PVC [Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease]). In conclusion, CA seems to reduce recurrence, burden, and frequency of PVCs compared with AADs. There is a lack of data on patient- and health care-specific outcomes such as symptoms, quality of life, and cost-effectiveness. Several upcoming trials will offer important insights for management of PVCs.

Consecutive Experience with Left Bundle Branch Area Pacing in a High-Volume Australian Centre.

INTRODUCTION: Left-bundle branch area pacing (LBBAP) is a relatively new technique for conduction system pacing. Australian safety and efficacy data is currently lacking. We aim to evaluate the learning curve, medium-term safety, and lead performance in a high-volume Australian setting. METHODS: We performed a retrospective cohort study of 200 consecutive LBBAP procedures performed by a single operator at two centres between January 2019 and May 2020. Left bundle branch area pacing was performed predominantly via left subclavian access using a 69 cm Medtronic SelectSecure 3830 pacing lead and a preformed non-steerable C315-His sheath. Procedural success was defined as evidence of left septal or left bundle branch area capture as evidenced by a right bundle branch block-like paced morphology. Procedural characteristics, and follow-up (including lead performance) data were collected. Procedural efficiency over time, as well as safety data, were collected. RESULTS: Median age was 78.26 years (interquartile range [IQR] 71-85), 37% were female. Atrial fibrillation was present in 22%. The left ventricular ejection fraction <50% in 24%, atrioventricular (AV) block was present in 43.5%, left bundle branch block in 22.5% and right bundle branch block in 24.5%. Acute procedural success was 91.5%. Implant threshold was 0.6V @ 0.5 ms, and 0.75V @ 0.5 ms at 11.9 months of follow-up. The QRS was significant reduced (baseline 134 ms vs implant 114 ms, p<0.001) There was a reduction in procedural time and X-ray dose over the course of the study. There were no complications specific to LBBAP. CONCLUSION: LBBAP appears to be a safe and effective pacing strategy. The QRS duration was significantly reduced compared to baseline. There appears to be an early learning curve with LBBAP.

A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

Association of interventricular activation delay with clinical outcomes in cardiac resynchronization therapy.

BACKGROUND: Pacing at sites of longest interventricular delay has been associated with greater reverse remodeling in cardiac resynchronization therapy (CRT). However, the effects of pacing at such sites on clinical outcomes is less well studied. OBJECTIVE: The purpose of this study was to assess the association between interventricular delay and clinical outcomes in CRT patients implanted with quadripolar left ventricular (LV) leads. METHODS: RALLY-X4 was a registry study of the Acuity X4 quadripolar LV leads. Interventricular delay was measured during unpaced basal rhythm from the right ventricular (RV) lead to the LV lead electrode (E1 to E4) chosen for CRT pacing. Patients were stratified by median RV-LV delay (80 ms) into short and long delay groups; they also were analyzed by multivariable modeling. The primary composite outcome measure was all-cause mortality and heart failure hospitalization (HFH) at 18 months. RESULTS: A total of 581 patients had complete RV-LV delay data. Mean LV ejection fraction was 27%, and 73% had typical left bundle branch block. Predictors of long RV-LV delay included female sex, left bundle branch block, and QRS duration >150 ms. Survival free of the primary outcome at 18-month follow-up was 87% in the long activation delay group compared with 77% in the short delay group (P = .0042). Multivariate analysis showed that RV-LV delay was an independent predictor of survival free of HFH (P = .028). CONCLUSION: Among CRT patients with quadripolar LV pacing leads, longer baseline interventricular activation delay was significantly associated with the composite endpoint of all-cause mortality and HFH.

Characterization of high-density mapping in catheter ablation for persistent atrial fibrillation: results from the Advisor™ HD Grid Mapping Catheter Observational study.

BACKGROUND: We quantified and characterized the outcomes of ablation in persistent atrial fibrillation (PersAF) subjects, and the utility of electroanatomical mapping with a market-released high-density (HD) mapping catheter. METHODS: PersAF subjects received electroanatomical mapping with the Advisor™ HD Grid mapping catheter, Sensor Enabled™ (HD Grid) and radiofrequency (RF) ablation to gather data regarding ablation strategies, mapping efficiency, quality, and outcomes. Subjects were enrolled from January 2019 to April 2020 across 25 international sites and followed for 12 months after the procedure. RESULTS: Three hundred thirty-four PersAF subjects (average age 64.2 years; 76% male; 25.4% previous AF ablation) were enrolled. Multiple map types were generated in a variety of rhythms using HD Grid. Significant differences in low voltage areas were identified in maps generated with the HD Wave Solution™ electrode configuration when compared to the standard configuration, which in some cases, influenced physicians' ablation strategies. PV-only ablation strategy was used in 59.0% of subjects and 34.1% of subjects received PV ablation and additional lesions. Of the subjects, 82.0% were free from recurrent atrial arrhythmias at 12 months and new or increased dose of class I/III antiarrhythmic drugs. About 6.0% of subjects experienced a serious adverse event or serious adverse device effect through 12 months including 1 event deemed related to HD Grid and the index procedure by the investigator and 1 death unrelated to study devices. CONCLUSIONS: The results of this study (NCT03733392) support the safety and utility of electroanatomical mapping with HD Grid in subjects with complex arrhythmias, such as PersAF in the real-world setting.

The extravascular implantable cardioverter-defibrillator: characterization of anatomical parameters impacting substernal implantation and defibrillation efficacy.

AIMS: The aim of this study is to provide a thorough, quantified assessment of the substernal space as the site of extravascular implantable cardioverter-defibrillator (ICD) lead placement using computed tomography (CT) scans and summarizing adverse events and defibrillation efficacy across anatomical findings. Subcutaneous ICDs are an alternative to transvenous defibrillators but have limitations related to ICD lead distance from the heart. An alternative extravascular system with substernal lead placement has the potential to provide defibrillation at lower energy and pacing therapies from a single device. METHODS AND RESULTS: A multi-centre, non-randomized, retrospective analysis of 45 patient CT scans quantitatively and qualitatively assessing bony, cardiac, vascular, and other organ structures from two human clinical studies with substernal lead placement. Univariate logistic regression was used to evaluate 15 anatomical parameters for impact on defibrillation outcome and adjusted for multiple comparisons. Adverse events were summarized. Substernal implantation was attempted or completed in 45 patients. Defibrillation testing was successful in 37 of 41 subjects (90%) using ≥10 J safety margin. There were two intra-procedural adverse events in one patient, including reaction to anaesthesia and an episode of transient atrial fibrillation during ventricular fibrillation induction. Anatomical factors associated with defibrillation failure included large rib cage width, myocardium extending very posteriorly, and a low heart position in the chest (P-values <0.05), though not significant adjusting for multiple comparisons. CONCLUSION: Retrospective analysis demonstrates the ability to implant within the substernal space with low intra-procedural adverse events and high defibrillation efficacy despite a wide range of anatomical variability.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.

An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

Safety and Efficacy of Leadless Pacemakers: A Systematic Review and Meta-Analysis.

Background Leadless pacemaker is a novel technology, and evidence supporting its use is uncertain. We performed a systematic review and meta-analysis to examine the safety and efficacy of leadless pacemakers implanted in the right ventricle. Methods and Results We searched PubMed and Embase for studies published before June 6, 2020. The primary safety outcome was major complications, whereas the primary efficacy end point was acceptable pacing capture threshold (≤2 V). Pooled estimates were calculated using the Freedman-Tukey double arcsine transformation. Of 1281 records screened, we identified 36 observational studies of Nanostim and Micra leadless pacemakers, with most (69.4%) reporting outcomes for the Micra. For Micra, the pooled incidence of complications at 90 days (n=1608) was 0.46% (95% CI, 0.08%-1.05%) and at 1 year (n=3194) was 1.77% (95% CI, 0.76%-3.07%). In 5 studies with up to 1-year follow-up, Micra was associated with 51% lower odds of complications compared with transvenous pacemakers (3.30% versus 7.43%; odds ratio [OR], 0.49; 95% CI, 0.34-0.70). At 1 year, 98.96% (95% CI, 97.26%-99.94%) of 1376 patients implanted with Micra had good pacing capture thresholds. For Nanostim, the reported complication incidence ranged from 6.06% to 23.54% at 90 days and 5.33% to 6.67% at 1 year, with 90% to 100% having good pacing capture thresholds at 1 year (pooled result not estimated because of the low number of studies). Conclusions Most studies report outcomes for the Micra, which is associated with a low risk of complications and good electrical performance up to 1-year after implantation. Further data from randomized controlled trials are needed to support the widespread adoption of these devices in clinical practice.

Electrophysiologic and imaging evidence for an occult myopathic substrate in patients with idiopathic ventricular arrhythmias.

BACKGROUND: Idiopathic VA are traditionally considered benign, although occasional patients develop an ectopy-mediated cardiomyopathy (EMC). It is unclear whether patients with idiopathic VA in the absence of left ventricular (LV) dysfunction harbor a subclinical cardiomyopathy. We aim to assess for cardiomyopathic substrate in patients with idiopathic ventricular arrhythmias (VA) using imaging and electrophysiologic markers of early fibrosis. METHODS: Cardiac magnetic resonance (CMR) imaging and ventricular electroanatomic mapping was performed in 3 groups: patients undergoing ablation for idiopathic VA without (Group 1, n = 17) and with LV dysfunction (Group 2 [presumed EMC], n = 12) plus a control group undergoing ablation of supraventricular tachycardia (Group 3, n = 16). Global LV strain, T1 mapping and extended electrogram (EGM) characteristics were compared. RESULTS: Global strain was impaired in patients with presumed EMC (Group 2, p < 0.001). Native T1 times did not differ between groups, however patients in both idiopathic VA groups (Groups 1 and 2) had shorter post-contrast T1 times at 8 min compared to SVT controls (Group 3, p = 0.04). Similarly, the duration of the bipolar EGM was subtly prolonged in both Group 1 and 2 compared to Group 3 (p = 0.002). There were no between group differences in unipolar or bipolar voltage, the no. of bipolar EGM deflections or the maximal unipolar EGM dV/dt. CONCLUSION: Patients with idiopathic VAs and apparently structurally normal hearts may have subtle CMR and electrophysiologic changes similar in magnitude to that seen in frank presumed EMC, possibly suggestive of an occult cardiomyopathic process.

Design and Preliminary Results of Sensing and Detection for an Extravascular Implantable Cardioverter-Defibrillator.

OBJECTIVES: This study reports the sensing and arrhythmia detection performance of a novel extravascular (EV) implantable cardioverter-defibrillator (ICD) in a first-in-human pilot study. BACKGROUND: The EV ICD lead is implanted in the substernal space, resulting in novel sensing and detection challenges. It uses a programmable sensing profile with new or modified discrimination of oversensing and of ventricular tachycardia (VT) from supraventricular tachycardia (SVT). METHODS: Electrograms were post-processed from induced ventricular fibrillation (VF) at implant to determine virtual detection times for each programmable sensitivity and the least-sensitive safe sensitivity setting. In ambulatory patients, programmed sensitivity provided at least a twofold safety margin for detecting induced VF. Noise discrimination was stress tested, and the effects of source, posture, and lead maturation were determined on electrogram amplitude. Telemetry Holter monitors were used to quantify undersensing and oversensing. RESULTS: In 20 patients at implant, the least-sensitive safe sensitivity for VF detection ranged from 0.1 to 0.6 mV. Seventeen patients were followed up for a total of 16.6 patient-years. Electrogram amplitudes were stable over time, but there were significant differences among postures and sensing vectors. For the primary sensing vector, the weighted oversensing and undersensing rates were 1.03% and 0.40% respectively, on a beat-to-beat basis. Oversensing did not cause inappropriate therapy in patients with in situ leads. Oversensing discriminators withheld VF detection in 4 of 5 spontaneous, sustained oversensed episodes. SVT-VT discriminators correctly classified 93% of 128 sustained SVTs in monitor zones. CONCLUSIONS: In the EV ICD pilot study, oversensing did not cause inappropriate therapy during ambulatory follow-up of stable leads.

Intracardiac Echocardiography to Guide Mapping and Ablation of Arrhythmias in Patients with Congenital Heart Disease.

Catheter ablation of arrhythmias in congenital heart disease can be a challenging undertaking with often complicated anatomic considerations. Understanding this anatomy and the prior surgical repairs is key to procedural planning and a successful outcome. Intracardiac echocardiography (ICE) adds complimentary real-time visualization of anatomy and catheter positioning along with other imaging modalities. In addition, ICE can visualize suture lines, baffles, and conduits from repaired congenital heart disease and forms a useful part of the toolkit required to deal with these complex arrhythmias.

Effects of omecamtiv mecarbil on failing human ventricular trabeculae and interaction with (-)-noradrenaline.

Omecamtiv mecarbil (OM) is a novel medicine for systolic heart failure, targeting myosin to enhance cardiomyocyte performance. To assist translation to clinical practice we investigated OMs effect on explanted human failing hearts, specifically; contractile dynamics, interaction with the ß1 -adrenoceptor (AR) agonist (-)-noradrenaline and spontaneous contractions. Left and right ventricular trabeculae from 13 explanted failing hearts, and trabeculae from 58 right atrial appendages of non-failing hearts, were incubated with or without a single concentration of OM for 120 min. Time to peak force (TPF) and 50% relaxation (t50% ) were recorded. In other experiments, trabeculae were observed for spontaneous contractions and cumulative concentration-effect curves were established to (-)-noradrenaline at ß1 -ARs in the absence or presence of OM. OM prolonged TPF and t50% in ventricular trabeculae (600 nM, 2 µM, p < .001). OM had no significant inotropic effect but reduced time dependent deterioration in contractile strength compared to control (p < .001). OM did not affect the generation of spontaneous contractions. The potency of (-)-noradrenaline (pEC50 6.05 ± 0.10), for inotropic effect, was unchanged in the presence of OM 600 nM or 2 µM. Co-incubation with (-)-noradrenaline reduced TPF and t50% , reversing the negative diastolic effects of OM. OM, at both 600 nM and 2 µM, preserved contractile force in left ventricular trabeculae, but imparted negative diastolic effects in trabeculae from human failing heart. (-)-Noradrenaline reversed the negative diastolic effects, co-administration may limit the titration of inotropes by reducing the threshold for ischemic side effects.