Publications
Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleCiaccio EJ, Peters NS, Garan H, 2018,
Use of an automaton model to suggest methods for cessation of intractable fibrillatory activity
, Computers in Biology and Medicine, Vol: 102, Pages: 357-368, ISSN: 0010-4825BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia, and permanent AF is an intractable medical problem. If cessation of permanent AF were possible, via extensive substrate ablation or multisite stimulation, it could significantly improve the public health. METHOD: A cellular automaton composed of 576 × 576 computerized grid nodes, described in detail previously, was used to test hypotheses concerning the cessation of fibrillatory electrical activity. A refractory period gradient across the grid, and addition of randomly located nonconducting fibers, were utilized as conditions leading to fibrillatory activity. A premature S1-S2 stimulus was applied to one grid corner, resulting in unidirectional conduction block at some locations, followed by rotational activity and random propagation of activation wavelets throughout the grid, none of which terminated spontaneously. Simulated ablation lesions of dimension 20 × 20 grid nodes, imparted at core locations of rotational activity, and multisite electrode stimulation (MES) applied at nodes where recovery of excitability had occurred, were used in attempts to terminate fibrillatory activity. Six impositions of random fiber location were utilized in separate trials. RESULTS: Simulated ablation lesions eliminated the targeted swirling vortices; however, additional vortices then often appeared at other locations. After ablating approximately one third of the grid area, localized vortices were eliminated, but individual wavelets continued to propagate about longer viable pathways forming at ablation lesions. Thus extensive ablation was unsuccessful in terminating arrhythmia. However, MES applied uniformly throughout the grid, with a coupling interval slightly longer than the maximum refractory period, terminated fibrillatory activity in some trials. More efficaciously, application of MES with a coupling interval half the maximum refractory period of the grid succeeded in capture of activation
-
Journal articleFerreira-Martins J, Howard J, Al-Khayatt BM, et al., 2018,
Outcomes of paroxysmal AF ablation studies are affected more by study design and patient mix than ablation technique
, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1471-1479, ISSN: 1045-3873Objective: We tested whether ablation methodology and study design can explain the varying outcomes in terms of AF-free survival at 1 year.Background:There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta-regression.Methods: Data was collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta-regression using the individual study arm as the unit.Results: Success rates did not change regardless of the technique used to produce pulmonary vein isolation. Neither were adjunctive lesion sets associated with any improvement in outcome.Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. ECG method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%, p<0.001) or in patients who had implantable loop recorders (by 21%, p=0.006), rather than less thorough periodic Holter monitoring.Conclusions: Outcomes of AF ablation studies involving pulmonary vein isolation are not affected by the technologies used to produce PVI. Neither do adjunctive lesion sets change the outcome. Achieving high success rates in these studies appears to be dependent more on patient mix and on the thoroughness of AF detection protocols. This should be carefully considered when quoting success rates of AF ablation procedures which are derived from such studies.
-
Journal articleSattler S, Ng FS, Panahi M, 2018,
Immunopharmacology of post-myocardial infarction and heart failure medications
, Journal of Clinical Medicine, Vol: 7, ISSN: 2077-0383The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, β-blockers, and renin–angiotensin–aldosterone inhibitors.
-
Journal articleRoney C, Ng FS, Debney M, et al., 2018,
Determinants of new wavefront locations in cholinergic atrial fibrillation
, EP-Europace, Vol: 20, Pages: iii3-iii15, ISSN: 1099-5129AimsAtrial fibrillation (AF) wavefront dynamics are complex and difficult to interpret, contributing to uncertainty about the mechanisms that maintain AF. We aimed to investigate the interplay between rotors, wavelets, and focal sources during fibrillation.Methods and resultsArrhythmia wavefront dynamics were analysed for four optically mapped canine cholinergic AF preparations. A bilayer computer model was tuned to experimental preparations, and varied to have (i) fibrosis in both layers or the epicardium only, (ii) different spatial acetylcholine distributions, (iii) different intrinsic action potential duration between layers, and (iv) varied interlayer connectivity. Phase singularities (PSs) were identified and tracked over time to identify rotational drivers. New focal wavefronts were identified using phase contours. Phase singularity density and new wavefront locations were calculated during AF. There was a single dominant mechanism for sustaining AF in each of the preparations, either a rotational driver or repetitive new focal wavefronts. High-density PS sites existed preferentially around the pulmonary vein junctions. Three of the four preparations exhibited stable preferential sites of new wavefronts. Computational simulations predict that only a small number of connections are functionally important in sustaining AF, with new wavefront locations determined by the interplay between fibrosis distribution, acetylcholine concentration, and heterogeneity in repolarization within layers.ConclusionWe were able to identify preferential sites of new wavefront initiation and rotational activity, in order to determine the mechanisms sustaining AF. Electrical measurements should be interpreted differently according to whether they are endocardial or epicardial recordings.
-
Journal articleLagarto J, Dyer B, Talbot C, et al., 2018,
Characterization of NAD(P)H and FAD autofluorescence signatures in a Langendorff isolated-perfused rat heart model
, Biomedical Optics Express, Vol: 9, Pages: 4978-4978, ISSN: 2156-7085Autofluorescence spectroscopy is a promising label-free approach to characterize biological samples with demonstrated potential to report structural and biochemical alterations in tissues in a number of clinical applications. We report a characterization of the ex vivo autofluorescence fingerprint of cardiac tissue, exploiting a Langendorff-perfused isolated rat heart model to induce physiological insults to the heart, with a view to understanding how metabolic alterations affect the autofluorescence signals. Changes in the autofluorescence intensity and lifetime signatures associated with reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) were characterized during oxygen- or glucose-depletion protocols. Results suggest that both NAD(P)H and FAD autofluorescence intensity and lifetime parameters are sensitive to changes in the metabolic state of the heart owing to oxygen deprivation. We also observed changes in NAD(P)H fluorescence intensity and FAD lifetime parameter on reperfusion of oxygen, which might provide information on reperfusion injury, and permanent tissue damage or changes to the tissue during recovery from oxygen deprivation. We found that changes in the autofluorescence signature following glucose-depletion are, in general, less pronounced, and most clearly visible in NAD(P)H related parameters. Overall, the results reported in this investigation can serve as baseline for future investigations of cardiac tissue involving autofluorescence measurements.
-
Journal articleVirag N, Erickson M, Taraborrelli P, et al., 2018,
Predicting vasovagal syncope from heart rate and blood pressure: A prospective study in 140 subjects
, Heart Rhythm, Vol: 15, Pages: 1404-1410, ISSN: 1547-5271BACKGROUND: We developed a vasovagal syncope (VVS) prediction algorithm for use during head-up tilt with simultaneous analysis of heart rate (HR) and systolic blood pressure (SBP). We previously tested this algorithm retrospectively in 1155 subjects, showing sensitivity 95%, specificity 93% and median prediction time of 59s. OBJECTIVE: This study was prospective, single center, on 140 subjects to evaluate this VVS prediction algorithm and assess if retrospective results were reproduced and clinically relevant. Primary endpoint was VVS prediction: sensitivity and specificity >80%. METHODS: In subjects, referred for 60° head-up tilt (Italian protocol), non-invasive HR and SBP were supplied to the VVS prediction algorithm: simultaneous analysis of RR intervals, SBP trends and their variability represented by low-frequency power generated cumulative risk which was compared with a predetermined VVS risk threshold. When cumulative risk exceeded threshold, an alert was generated. Prediction time was duration between first alert and syncope. RESULTS: Of 140 subjects enrolled, data was usable for 134. Of 83 tilt+ve (61.9%), 81 VVS events were correctly predicted and of 51 tilt-ve subjects (38.1%), 45 were correctly identified as negative by the algorithm. Resulting algorithm performance was sensitivity 97.6%, specificity 88.2%, meeting primary endpoint. Mean VVS prediction time was 2min 26s±3min16s with median 1min 25s. Using only HR and HR variability (without SBP) the mean prediction time reduced to 1min34s±1min45s with median 1min13s. CONCLUSION: The VVS prediction algorithm, is clinically-relevant tool and could offer applications including providing a patient alarm, shortening tilt-test time, or triggering pacing intervention in implantable devices.
-
Journal articleCook CM, Ahmad Y, Howard JP, et al., 2018,
Impact of percutaneous revascularization on exercise hemodynamics in patients with stable coronary disease
, Journal of the American College of Cardiology, Vol: 72, Pages: 970-983, ISSN: 0735-1097BACKGROUND: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD). OBJECTIVES: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD. METHODS: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles. RESULTS: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001). CONCLUSIONS: In patients with SCD and severe single-vessel stenosis, objective physiological
-
Journal articleMalhotra A, Dhutia H, Finocchiaro G, et al., 2018,
Outcomes of cardiac screening in adolescent soccer players
, New England Journal of Medicine, Vol: 379, Pages: 524-534, ISSN: 0028-4793BackgroundReports on the incidence and causes of sudden cardiac death among young athletes have relied largely on estimated rates of participation and varied methods of reporting. We sought to investigate the incidence and causes of sudden cardiac death among adolescent soccer players in the United Kingdom.MethodsFrom 1996 through 2016, we screened 11,168 adolescent athletes with a mean (±SD) age of 16.4±1.2 years (95% of whom were male) in the English Football Association (FA) cardiac screening program, which consisted of a health questionnaire, physical examination, electrocardiography, and echocardiography. The FA registry was interrogated to identify sudden cardiac deaths, which were confirmed with autopsy reports.ResultsDuring screening, 42 athletes (0.38%) were found to have cardiac disorders that are associated with sudden cardiac death. A further 225 athletes (2%) with congenital or valvular abnormalities were identified. After screening, there were 23 deaths from any cause, of which 8 (35%) were sudden deaths attributed to cardiac disease. Cardiomyopathy accounted for 7 of 8 sudden cardiac deaths (88%). Six athletes (75%) with sudden cardiac death had had normal cardiac screening results. The mean time between screening and sudden cardiac death was 6.8 years. On the basis of a total of 118,351 person-years, the incidence of sudden cardiac death among previously screened adolescent soccer players was 1 per 14,794 person-years (6.8 per 100,000 athletes).ConclusionsDiseases that are associated with sudden cardiac death were identified in 0.38% of adolescent soccer players in a cohort that underwent cardiovascular screening. The incidence of sudden cardiac death was 1 per 14,794 person-years, or 6.8 per 100,000 athletes; most of these deaths were due to cardiomyopathies that had not been detected on screening. (Funded by the English Football Association and others.)
-
Journal articleKyriacou A, Rajkumar CA, Pabari P, et al., 2018,
Distinct impacts of heart rate and right atrial-pacing on left atrial mechanical activation and optimal AV delay in CRT
, Pacing and Clinical Electrophysiology, Vol: 41, Pages: 959-966, ISSN: 0147-8389AbstractBackgroundControversy exists regarding how atrial activation mode and heart rate affect optimal AV delay in cardiac resynchronisation therapy. We studied these questions using high‐reproducibility haemodynamic and echocardiographic measurements.Methods20 patients were hemodynamically optimized using non‐invasive beat‐to‐beat blood pressure at rest (62±11 bpm), during exercise (80±6 bpm) and at 3 atrially‐paced rates: 5, 25 and 45 bpm above rest, denoted Apaced,r+5, Apaced,r+25 and Apaced,r+45 respectively. Left atrial myocardial motion and transmitral flow were timed echocardiographically.ResultsDuring atrial‐sensing, raising heart rate shortened optimal AV delay by 25±6 ms (p < 0.001). During atrial pacing, raising heart rate from Apaced,r+5 to Apaced,r+25 shortened it by 16±6 ms; Apaced,r+45 shortened it 17±6 ms further (p < 0.001).In comparison to atrial‐sensed activation, atrial pacing lengthened optimal AV delay by 76±6 ms (p < 0.0001) at rest, and at ∼20 bpm faster, by 85±7 ms (p < 0.0001), 9±4 ms more (p = 0.017). Mechanically, atrial pacing delayed left atrial contraction by 63±5 ms at rest and by 73±5 ms (i.e. by 10±5 ms more, p < 0.05) at ∼20 bpm faster.Raising atrial rate by exercise advanced left atrial contraction by 7±2 ms (p = 0.001). Raising it by atrial pacing did not (p = 0.2).ConclusionsHemodynamic optimal AV delay shortens with elevation of heart rate. It lengthens on switching from atrial‐sensed to atrial‐paced at the same rate, and echocardiography shows this sensed‐paced difference in optima results from a sensed‐paced difference in atrial electromechanical delay.The reason for the widening of the sensed‐paced difference in AV optimum may be physiological stimuli (e.g. adrenergic drive) advancing left atrial contraction during exercise but not with fast atrial pacing.
-
Journal articleLuther V, Wright I, Lefroy D, et al., 2018,
A narrow complex tachycardia with variable R-R intervals: what is the mechanism?
, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1174-1176, ISSN: 1045-3873A 46-year-old man was referred for an invasive electrophysiological study with a view to ablation, for a history of classic sudden onset-offset palpitations. The patient’s son had recently survived an out of hospital cardiac arrest, and was found to have an accessory pathway (details unknown) at another institute, which was ablated. Our patient’s 12 lead electrocardiogram (ECG) showed sinus rhythm with no evidence of pre-excitation. Echocardiography revealed a structurally normal heart. An electrophysiological study was performed with a quadripolar catheter positioned at the high right atrium (HRA), a steerable decapolar catheter in the coronary sinus and quadripolar catheters along the His bundle and at the right ventricular apex. Baseline atrio-His (AH) and His-ventricular (HV) intervals measured 60ms and 40ms respectively. Programmed atrial extra-stimulus testing revealed decremental AH intervals, before tachycardia was reproducibly induced. Figure 1 shows the tachycardia on a 12-lead ECG. Figure 2 shows the induction of tachycardia with atrial pacing. Based on the findings within the figures, what is the mechanism of the tachycardia?
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.