Search

Objectives This study sought to assess immediate and short-term performance of the Medtronic Attain Stability Quadripolar 4798 lead (Medtronic, Dublin, Ireland). Background Cardiac resynchronization therapy (CRT) is an established treatment for appropriately selected patients with left ventricular (LV) systolic dysfunction. The most common reason for failure to implant a lead is the lack of a suitable epicardial vein, due either to an absent vessel in the target site, an unacceptably high threshold, lead instability, phrenic nerve stimulation, or a combination of reasons. In August 2017, a novel quadripolar active fixation LV lead (Medtronic) was released. This paper reports the initial clinical experience with lead implantation and specifically immediate and short-term pacing parameters across 3 United Kingdom centers. Methods Consecutive patients eligible for CRT were deemed suitable for this lead. Immediate and short-term lead performance data regarding LV threshold, impedance, and displacement rates were collected at standard pacing checks (1 day, 5 weeks, 3 months, and 9 months post-implantation). Results CRT using this lead was attempted in 82 cases and was successful in 81 cases (98.8%). LV thresholds and impedance levels were 1.22 ± 0.75 V and 737 ± 319 Ω at implantation; 1.16 ± 0.71 V and 597 ± 218 Ω at day 1; 1.02 ± 0.48 V and 579 ± 148 Ω at week 6; 0.98 ± 0.49 V and 569 ± 133 Ω at 3 months; and 1.06 ± 0.48 V and 570 ± 140 Ω at 9 months. As of the publication of this paper, no LV lead has been displaced. Conclusions CRT using the Medtronic lead was successful in more than 98% of the patients. Short-to-medium-term data regarding lead performance and stability were excellent, with zero displacements as of the publication of this paper.

Background: Catheter-tissue contact force is an important factor influencing lesion size and efficacy and thereby potential for arrhythmia recurrence following accessory pathway (AP) radiofrequency ablation. We aim to evaluate adequacy and perception of catheter contact on the tricuspid and mitral annuli. Methods: Data were collected from 42 patients undergoing catheter ablation. Operators were blinded to contact force information and reported perceived contact (poor, moderate, or good) while positioning the catheter at four tricuspid annular sites (12, 9, 6 and 4 o'clock positions; abbreviated as TA12, TA9, TA6 and TA4) and three mitral annular sites (3, 5 and 7 o'clock positions; abbreviated as MA3, MA5 and MA7) through long vascular sheaths. Results: The highest and lowest mean contact forces were obtained at MA7 (13.3 ± 1.7 g) and TA12 (3.6 g ± 1.3 g) respectively. Mean contact force on tricuspid annulus (6.1 g ± 0.9 g) was lower than mitral annulus (9.8 ± 0.9 g) locations (p = 0.0036), with greater proportion of sites with

Funding Acknowledgements No financial support for this study Introduction Permanent pacemaker implantation combined with AVN ablation is a well-established treatment for rate control in patients with atrial fibrillation refractory to medical therapy. At the same sitting, this has been achieved in a single procedure via the subclavian vein (SCV) for both pacemaker implantation and AVN ablation, by pacemaker implantation via the SCV with femoral access for AVN ablation or by using the femoral vein (FV) for leadless pacemaker implantation and AVN ablation with a coaxial single-puncture technique. We evaluated all combined procedures (pacemaker implantation and AVN ablation at the same sitting) performed in a single centre over 9 years comparing clinical outcomes, complications rates and procedure times. Statistical methods: Continuous variables are described as mean ± standard deviation (SD), and statistical differences between groups were evaluated by one-way ANOVA. A X2 test was used for categorical variables, with Fisher’s exact test for any field where the expected frequency was ≤5 with pvalue < 0.05 considered as statistically significant. The statistical analysis was performed using SPSS software package. Results 141 patients underwent AVN ablation at our institution as part of a ‘pace and ablate’ single procedure strategy between 14/2/11 and 10/6/19. 61 patients had a combined procedure via the SCV, 66 patients had pacemaker implanted via the SCV and AVN ablation via the FV in the same sitting and 14 patients had leadless pacemaker (Micra) implantation and AVN ablation via the FV. Our findings suggest that the fluoroscopy time as well as the total catheter laboratory time were much less in the Micra group compared to the other groups. In the conventional pacemaker groups (group 1 and 2), the fluoroscopy time was not statistically different between the two. There was a trend towards acute procedural failure, switching to another access as well as a higher complication rate in the SCV group, however this has not reached statistical significance. Conclusion Our early data suggests that pacemaker implantation and AVN ablation with a coaxial single femoral vein puncture technique is safe and takes less fluoroscopy time as well as total laboratory time. Procedural outcomes All (n = 141) Group 1: SCV (n = 61) Group 2: FV (n = 66) Group 3: Micra (n = 14) P-value Total cath-lab time (mins) 113.1 ± 40.4 106.2 ± 37.2 125.7 ± 42.5 86.9 ± 23.1 0.001 Total fluoroscopy time (mins) 8.8 ± 7.6 11 ± 7.8 7.7 ± 7.6 4.5 ± 3 0.0001 Acute procedural failure, n (%) 9 (6.4) 7 (11.5) 2 (3) 0 (0) **0.6 Complications, n (%) 7 (4.9) 5 (8.2) 2 (3) 0 (0) **0.62 **Fisher"s exact test applied to analysis of Micra VS Other methods

OnBehalf United Kingdom Cardiac SABR consortium Background Stereotactic Ablative Body Radiotherapy (SABR) is a novel non-invasive treatment for Ventricular Tachycardia (VT) refractory to standard catheter ablation. 3 UK hospitals have started compassionate use cardiac SABR programmes, and are working in close collaboration. Purpose To report initial UK experience for treatment of refractory VT with cardiac SABR. Methods All patients had undergone prior unsuccessful invasive ablation with VT recurrence despite anti-arrhythmic drug (AAD) use. High-resolution CT imaging with 3D reconstruction was combined with 12 lead ECGs of VT and prior invasive +/- non-invasive electrophysiology mapping data to define a cardiac target. Treatment margins were modified to account for cardiac/respiratory motion and to minimise off target treatment to other organs as per clinical SABR practice. Single fraction high dose treatment (20-25 Gy) was delivered by CT guided Linear Accelerator. Patients were assessed regularly with clinical review and remote device monitoring. Results 3 patients have been treated so far with aetiologies of prior myocarditis, non-ischaemic dilated cardiomyopathy and ischaemic cardiomyopathy. All patients successfully received planned SABR treatment in Conclusions Cardiac SABR shows promise for VT control, but further experience and trials are needed. Integration of imaging and electrophysiology data to generate accurate targets appears critical. The effect of SABR seems to develop over several weeks after therapy. Patient selection and timing of SABR delivery is important with acknowledgement that competing causes of death exist in patients with refractory VT entering a compassionate use program. Abstract Figure. Example SBRT plan

BackgroundOptions for patients with ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or catheter ablation remain limited. Stereotactic radiotherapy has been described as a novel treatment option.MethodsSeven patients with recurrent refractory VT, deemed high risk for either first time or redo invasive catheter ablation, were treated across three UK centres with non-invasive cardiac stereotactic ablative radiotherapy (SABR). Prior catheter ablation data and non-invasive mapping were combined with cross-sectional imaging to generate radiotherapy plans with aim to deliver a single 25 Gy treatment. Shared planning and treatment guidelines and prospective peer review were used.ResultsAcute suppression of VT was seen in all seven patients. For five patients with at least 6 months follow-up, overall reduction in VT burden was 85%. No high-grade radiotherapy treatment-related side effects were documented. Three deaths (two early, one late) occurred due to heart failure.ConclusionsCardiac SABR showed reasonable VT suppression in a high-risk population where conventional treatment had failed.

Objectives Using high-resolution 3-dimensional (3D) mapping, the aim of this study was to further characterize right atrial macro–re-entrant tachycardias and answer unresolved questions in the understanding of this arrhythmia. Background Despite advances in understanding of the mechanisms of right atrial macro–re-entrant tachycardias, many questions lack definitive answers. The advent of high-resolution 3D mapping provides an opportunity to gain further insights into the nature of these common circuits. Methods A total of 25 patients with right atrial macro–re-entrant tachycardia were studied. High-resolution 3D mapping (Rhythmia mapping system, Boston Scientific, Natick, Massachusetts) was performed. Regional voltage and conduction velocity were determined. Maps were analyzed to characterize wave front propagation patterns in all atrial regions. The relationship between substrate and conduction was evaluated. Results A total of 42 right atrial macro–re-entrant circuits were observed. The most common location of the posterior line of block was the posteromedial right atrium (73%). This line of block continued superiorly into the superior vena cava, taking an oblique course to finish on the anterior superior vena cava aspect in 73%. Conduction delay at the crista terminalis was less common (23%). Conduction slowing or block was seen at the limbus of the fossa ovalis (73%) and Eustachian ridge (77%). Highly variable and localized areas of slow conduction were also observed in the inferior septum (45%), superior septum (27%), anterosuperior right atrium (23%), and lateral right atrium (23%). Localized conduction slowing was seen in the cavotricuspid isthmus in 50% of patients, but there was no generalized conduction slowing in this isthmus. The voltage in regions of slow conduction was significantly lower compared with areas of normal conduction velocity (p Conclusions High-resolution 3D mapping has provided new insights into the nature of right atrial macro–re-entrant tachycardias. Variable regions of abnormal atrial substrate were associated with conduction slowing and block. Individual variation in propagation patterns was observed in association with this variable substrate. (Mapping of Atrial Arrhythmias Using High Spatial Resolution Mapping Catheters and the Rhythmia Mapping System; ACTRN12615000544572)

SummaryPurpose This study assessed the agreement between cardiac output estimated by inert gas rebreathing and bioreactance methods at rest and during exercise. Methods Haemodynamic measurements were assessed in 20 healthy individuals (11 females, nine males; aged 32 ± 10 years) using inert gas rebreathing and bioreactance methods. Gas exchange and haemodynamic data were measured simultaneously under rest and different stages (i.e. 30, 60, 90, 120, 150 and 180 W) of progressive graded cardiopulmonary exercise stress testing using a bicycle ergometer. Results At rest, bioreactance produced significantly higher cardiac output values than inert gas rebreathing (7·8 ± 1·4 versus 6·5 ± 1·7 l min−1, P = 0·01). At low-to-moderate exercise intensities (i.e. 30–90 W), bioreactance produced significantly higher cardiac outputs compared with rebreathing method (P

Background A novel active fixation coronary sinus (CS) lead, Attain Stability, has been released in a bipolar and quadripolar configuration, with the hypothesis it will improve targeted lead positioning and stability independent of vessel anatomy. Purpose To compare implant procedure parameters and electrical performance/stability of a novel active fixation lead with passive fixation CS leads. Methods This was a retrospective study involving 6 major UK cardiac centres. Patients who received active leads were compared with passive lead recipients in a 1:2 ratio. The primary outcome was total lead displacements (combined macro/micro-displacements, defined as displacements requiring repositioning procedures, or an increase in threshold≥0.5 volts or pulse width≥0.5msec, or a change in pacing polarity). Multivariate analysis was performed to establish predictors of the primary outcome, assessing fixation mechanism (active or passive), number of poles (quad or bipolar), contributing hospital and follow-up duration. Results 736 patients were included (241 with active leads, 495 with passive leads). There were no group differences in the baseline characteristics with respect to age, gender, EF, NYHA class, and co-morbidities, P>0.05 for all. The primary endpoint rate was 31% (74/241) in the active and 43% (213/495) in the passive fixation group (P=0.002). 6 patients in the active group and 14 in the passive group required CS lead repositioning procedures. The results of the multivariate analysis are presented in the Table. The use of active leads was associated with a significant reduction in lead displacements, odds ratio 0.62 (95% CI 0.43–0.9), P=0.012. There were differences in favour of passive compared with active leads in procedure duration, 120 [96–149] minutes vs 128 [105–155] minutes (P=0.011), and fluoroscopy time, 17 [11–26] minutes vs 18.5 [13–27] minutes (P=0.028). The median duration of follow up was similar (active vs passive): 31 [17–47] weeks vs 34 [16–71] weeks, (P=0.052). Odds Ratio (95% Confidence Interval) P-value Active fixation CS lead 0.62 (0.43–0.9) 0.012 Quadripolar (rather than Bipolar) lead 1.26 (0.75–2.11) 0.376 Follow-up Duration (weeks) 1.005 (1.001–1.008) 0.025 Also included in the model: contributing hospital, which was significant. Conclusion In this large, multi-centre study, active fixation Attain Stability CS leads demonstrated superior electrical performance/stability compared with passive fixation leads, with minimal increases in implant procedure and fluoroscopy times. Acknowledgement/Funding None

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23–32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min−1, p=0.54; 114 (28) vs. 108 (15) ml beat−1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p

ObjectiveRegular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.MethodsAdult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.ResultsIn this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, pConclusionsOur findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease.

Background: Currently there are no known cures and few effective treatments for mitochondrial disorders. It is also true there is a lack of knowledge about suitable clinician rated outcomes and how these change over time in this patient cohort. Objective: We sought to evaluate the validity and responsiveness to change of clinician rated outcome measures in patients with m.3243A>G-related mitochondrial disease. Methods: We assessed the six minute timed walk (6MTW), 10 meter walk / test (10MWT), Timed up and Go (TUG) and the 5 times sit to stand (5XSTS), in 18 patients (12 sedentary controls), at baseline and a subgroup of 10 control-matched patients following a 16-week structured aerobic exercise intervention program. Results: All outcome measures assessed were valid and able to differentiate between patients and controls. Disease severity, as measured by the Newcastle Mitochondrial Disease Adult Scale, correlated with TUG (r = 0.54, p = 0.020) and 10MWT (r = 0.47, p = 0.050). Receiver Operating Curve analysis revealed 5XSTS to be the most responsive measure (AUC 0.931; 95% CI 0.84– 1.00) with responsiveness to change, post intervention, emulating disease burden variance. Conclusions: The 5XSTS can be used to discriminate between mitochondrial patients and sedentary controls with high accuracy. The 10MWT and TUG may serve as suitable and clinically relevant clinician rated measures to track disease progression and assess intervention.

Background: The use of pacemakers in the treatment of cardioinhibitory vasovagal syncope is controversial with a mixed message from the limited evidence base. Single chamber leadless pacemakers have been shown to be an effective alternative option to conventional pacemakers. Objective: This study examines the use of leadless pacemakers in a cardioinhibitory vasovagal population in the United Kingdom. Methods: Observational data on 32 patients implanted with the Micra Transcatheter Pacemaker System for vasovagal syncope are presented. Data was collected on implant indications, implant procedure and follow up data from 12 centres across the United Kingdom that had elected to use a Micra leadless pacemaker in this patient population. Results: 32 patients aged 37 ± 14 years (range 18 to 64 years) with 62% of the patients being female were recruited to the study. Vasovagal syncope was diagnosed clinically and with the support of Holter monitoring, tilt table testing and implantable loop recorders. The duration of symptoms was 8 ± 8 yrs. with an average frequency of syncope being 4 ± 6 times/year. The Micra pacemaker was successfully implanted in all patients with a major complication rate of 3.1%. Patients were followed up for 404 ± 237 days (range 63–928 days). At follow up 28 (87%) patients were free from symptoms. Conclusions: This observational study suggests that the use of a single chamber leadless pacemaker in the treatment of cardioinhibitory vasovagal syncope might be a reasonable clinical option. Keywords: Vasovagal, Cardioinhibitory, Syncope, Pacemaker, Leadless pacemaker, Micra

Mitochondrial disease is complex and variable, making diagnosis and management challenging. The situation is complicated by lack of sensitive outcomes of disease severity, progression, contributing pathology and clinical efficacy. Gait is emerging as a sensitive marker of pathology; however, to date, no studies have quantified gait in mitochondrial disease. In this cross-sectional study, we quantified gait characteristics in 24 patients with genetically confirmed mitochondrial disease (m.3243A>G and m.8344A>G) and 24 controls. Gait was measured using an instrumented walkway according to a predefined model with five domains hypothesised to reflect independent features of the neural control of gait in mitochondrial disease, including: pace (step velocity and step length); rhythm (step time); variability (step length and step time variability); asymmetry (step time asymmetry); and postural stability (step width, step width variability and step length asymmetry). Gait characteristics were compared with respect to controls and genotype. Additional measures of disease severity, pathophysiology and imaging were also compared to gait to verify the validity of gait characteristics. Discrete gait characteristics differed between controls and mitochondrial disease groups, even in relatively mildly affected patients harbouring the m.3243A>G mutation. The pattern of gait impairment (increased variability and reduced postural control) was supported by significant associations with measures of disease severity, progression, pathophysiology and radiological evidence of cerebellar atrophy. Discrete gait characteristics may help describe functional deficits in mitochondrial disease, enhance measures of disease severity and pathology, and could be used to document treatment effects of novel therapies.

Background Cardiac hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Endurance exercise training improves symptoms and skeletal muscle function, yet cardiac adaptations are unknown. Methods and results Before and after 16-weeks of training, exercise capacity, cardiac magnetic resonance imaging and phosphorus-31 spectroscopy, disease burden, fatigue, quality of life, heart rate variability (HRV) and blood pressure variability (BPV) were assessed in 10 adult patients with m.3243A>G-related mitochondrial disease, and compared to age- and gender-matched sedentary control subjects. At baseline, patients had increased left ventricular mass index (LVMI, p

Aim The mechanisms of cardiac dysfunction in limb girdle muscular dystrophy 2I (LGMD2I) are unclear. This study assessed deficits in cardiac morphology, function, and metabolism quantitatively in patients with a confirmed genetic diagnosis of the homozygous c.826C > A FKRP (fukutin-related protein) mutation, using a comprehensive magnetic resonance (MR) examination. Methods and results Ten patients (7 male and 3 female) and 10 matched control subjects were recruited prospectively. Cardiac morphology by cine imaging, cardiac torsion and strain by MR tagging, and cardiac energetics by phosphorus-31 MR spectroscopy were measured. LGMD2I subjects were found to have a significant reduction in peak cardiac torsion (3.9 ± 1.3° vs. 6.4 ± 1.5°, P = 0.04), and in the ratio of torsion to endocardial strain (0.31 ± 0.05 vs. 0.51 ± 0.14, P = 0.03), compared with control subjects. The impairment in torsion correlated strongly with reduction in EF (r = 0.93, P < 0.001). Peak circumferential and longitudinal strains were preserved in the patients, however [LGMD2I, 16.4 ± 3.2% vs. 18.3 ± 3.5%, non-significant (NS); and LGMD2I, 17.0 ± 3.0% vs. 18.4 ± 3.5%, NS]. Cardiac cine analysis demonstrated reduced EF (47 ± 7% vs, 58 ± 4%, P = 0.02) and stroke volume (61 ± 11 mL vs. 81 ± 13 mL, P = 0.04), though no evidence of LV hypertrophy was found. The ratio of phosphocreatine to ATP (PCr/ATP) was reduced in the LGMD2I subjects compared with controls (1.50 ± 0.24 vs. 1.94 ± 0.12, P = 0.0001). Conclusions The loss of torsion with preservation of circumferential and longitudinal strain in LGMD2I is a unique finding and suggests subepicardial dysfunction with abnormal transmission of force across the cardiac wall.

Aims Hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Screening strategies for cardiac disease are unclear. We investigated whether myocardial abnormalities could be identified in mitochondrial DNA mutation carriers without clinical cardiac involvement. Methods and results Cardiac magnetic resonance imaging was performed in 22 adult patients with mitochondrial disease due to the m.3243A>G mutation, but no known cardiac involvement, and 22 age- and gender-matched control subjects: (i) Phosphorus-31- magnetic resonance spectroscopy, (ii) cine imaging (iii), cardiac tagging and (iv) late gadolinium enhancement (LGE) imaging. Disease burden was determined using the Newcastle Mitochondrial Disease Adult Scale (NMDAS) and urinary mutation load. Compared with control subjects, patients had an increased left ventricular mass index (LVMI), LV mass to end-diastolic volume ( M / V ) ratio, wall thicknesses (all P < 0.01), torsion and torsion to endocardial strain ratio (both P < 0.05). Longitudinal shortening was decreased in patients ( P < 0.0001) and correlated with an increased LVMI ( r = −0.52, P < 0.03), but there were no differences in the diastolic function. Among patients there was no correlation of LVMI or the M / V ratio with diabetic or hypertensive status, but the mutation load and NMDAS correlated with the LVMI ( r = 0.71 and r = 0.79, respectively, both P < 0.001). The phosphocreatine/adenosine triphosphate ratio was decreased in patients ( P < 0.001) but did not correlate with other parameters. No patients displayed focal LGE. Conclusion Concentric remodelling and subendocardial dysfunction occur in patients carrying m.3243A>G mutation without clinical cardiac disease. Patients with higher mutation loads and disease burden may be at increased risk of cardiac involvement.

Mitochondrial disease refers to a heterogenous group of genetic disorders that result from dysfunction of the final common pathway of energy metabolism. Mitochondrial DNA mutations affect key components of the respiratory chain and account for the majority of mitochondrial disease in adults. Owing to critical dependence of the heart on oxidative metabolism, cardiac involvement in mitochondrial disease is common and may occur as the principal clinical manifestation or part of multisystem disease. Recent advances in our understanding of the clinical spectrum and genetic aetiology of cardiac involvement in mitochondrial DNA disease have important implications for cardiologists in terms of the investigation and multi-disciplinary management of patients.

The autoimmune liver disease primary biliary cirrhosis (PBC) is associated with life-altering fatigue in ∼50% of patients. Previous work suggests that fatigued PBC subjects have evidence of autonomic dysfunction and may be at a higher risk of sudden cardiac death. The manifestation of this risk is not clear. This pilot study investigated whether alterations in cardiac torsion and strain could be detected in fatigued or nonfatigued early-stage PBC patients. We performed cardiac tissue tagging and anatomical cine-imaging in 13 early-stage PBC patients (including 7 with significant fatigue) and 10 control subjects to calculate cardiac torsion and strain throughout systole and diastole. From the cardiac tagging, we calculated the torsion-to-shortening ratio (TSR), a measure of subepicardial torsion exerting mechanical advantage over subendocardial shortening. Autonomic function testing was performed to evaluate baroreceptor effective index on standing. TSR was markedly increased in the fatigued PBC patients (0.70 ± 0.13) compared with both controls (0.46 ± 0.11, P = 0.002) and nonfatigued PBC patients (0.44 ± 0.12, P = 0.003). Decreased baroreceptor effective index on standing strongly correlated with increased TSR within the whole PBC group ( r = −0.71, P = 0.007). Fatigued PBC patients demonstrate a redistribution of myocardial strain characteristic of a reduced relative contribution to contraction from the subendocardium. This is analogous to the changes found in healthy aging for subjects ∼16 yr older than the fatigued PBC patients. Hence the hearts of fatigued PBC patients may be subject to processes of accelerated aging.

A best evidence topic was written according to a structured protocol. The issue was to determine the incidence and predictors of postoperative permanent pacemaker (PPM) implantation in patients undergoing trans-catheter aortic valve implantation (TAVI) for symptomatic calcific aortic stenosis and to compare this to the known risks of this complication following surgical aortic valve replacement (AVR). Using the reported search method 3071 articles were identified, of which 94 were relevant to the procedure of TAVI and 14 were deemed to represent the best evidence. All 14 studies, including both multi-centre registries and single-centre retrospective case series containing ≥30 patients, reported incidence of postoperative PPM implantation. Five of these studies also assessed predictors of the need for postoperative PPM implantation. The author, journal, date and country of publication, study type, level of evidence, patient group, outcomes and results were tabulated for these studies. We conclude that the current best available evidence suggests that the mean incidence of PPM implantation following TAVI is 14.2% (range 0-34%, median 9.7%), although this appears higher with the CoreValve prosthesis (five studies, mean 20.8%, range 9.3-30.0%) than with the Edwards-Sapien prosthesis (six studies, mean 5.4%, range 0-10.1%). The mean incidences of PPM implantation overall and when using the CoreValve prosthesis are higher than the mean incidence of 7.0% (range 3-11.8%, median 7.2%) following conventional AVR and may be explained by distinct differences between the patient groups involved and the procedure performed. Indications for PPM implantation appear to occur early in the postoperative period following TAVI and there is little evidence of recovery following atrioventricular block (AVB). New onset persistent left bundle branch block is common following TAVI but the significance and follow-up required is unclear. Independent predictors of PPM requirement following TAVI include use of the CoreValve prosthesis and evidence of conduction system dysfunction, either pre-existing right bundle branch block or AVB at the time of TAVI. All patients should be made aware of the high risk of PPM implantation with TAVI.

Both tissue hypoxia in vitro, and whole-body hypoxia in vivo, have been found to promote the release of reactive oxygen species (ROS) that are potentially damaging to the cardiovascular system. Antioxidant systems protect against oxidative damage by ROS and may exhibit some degree of responsiveness to oxidative stimuli. Production of urate, a potent soluble antioxidant, is increased in hypoxic conditions. We aimed to determine whether urate is an important antioxidant defense in healthy subjects exposed to hypoxia.We conducted a cohort study of 25 healthy lowland volunteers during acute exposure to high altitude (4 days at 3,600 m, followed by 10 days at 5,200 m) on the Apex high-altitude research expedition to Bolivia. We measured markers of oxidative stress (8-isoprostane F2), serum urate concentration, and total plasma antioxidant activity by two techniques: 2,2'-amino-di-[3-ethylbenzthiazole sulfonate] spectrophotometry (total antioxidant status [TAS]) and enhanced chemiluminescence (ECL).On ascent, F2-isoprostane levels were significantly elevated compared with those at sea level (p0.01). After 1 week at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and serum urate concentration were significantly elevated (each p0.01 vs sea level), and F2-isoprostane levels were reduced to values at sea level. There was a highly significant correlation between plasma urate and AOC at this stage (ECL, r(2) = 0.59, p = 0.0001; TAS, r(2) = 0.30, p = 0.0062).Our results support the hypothesis that urate may act as a responsive endogenous antioxidant in high-altitude hypoxia.

Deglutition-induced atrial tachycardia is a rare arrhythmia with a poor response to medical therapy. Electrophysiological study is challenging due to the dependence of induction on swallowing. We present a novel approach to management of deglutition-induced atrial tachycardia arising from right superior pulmonary vein. Use of minimal conscious sedation and repeated swallow challenge inductions, together with contact force-guided mapping were key determinants of success. We review published cases, discussing potential mechanisms including oesophageal distension and neural reflexes.

Background Left ventricular epicardial lead placement via video-assisted thoracoscopy (VAT) is a recognized surgical technique to achieve cardiac resynchronization therapy (CRT) when conventional lead placement has failed. Its role in patients with previous sternotomy is uncertain. We describe our experience in a cohort of patients including those with previous sternotomy. Methods This was a retrospective review of consecutive patients undergoing VAT lead implantation for CRT in a single center between 2004 and 2011. All patients fulfilled conventional criteria for CRT and were followed up at 4 to 6 weeks and then at 3-month intervals. Clinical and pacing parameters were compared at baseline and at the latest review. Results Thirty-two patients (27 men; mean age, 67 ± 9 years) underwent VAT left ventricular lead implantation. Mean follow-up duration was 704 ± 450 days. Ten patients (31%) had undergone previous sternotomy. Thoracoscopic lead implantation was successful in 31 patients (97%): 1 patient with two previous sternotomies required conversion to open thoracotomy due to bleeding with multiple adhesions. Satisfactory implantation pacing thresholds of 2 volts or less at 0.5 ms were achieved in all patients. Despite a longer operative time in those with previous sternotomy, all clinical and pacing outcomes, including complications, clinical response to CRT, and long-term pacing variables were similar between the groups. Conclusions VAT left ventricular lead placement appears safe and effective in selected patients with previous sternotomy, including coronary artery bypass operations, with postoperative outcomes comparable with those patients without previous sternotomy.

Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development of high altitude pulmonary edema (HAPE). Due to its effectiveness as a pulmonary vasodilator, sildenafil has been proposed as a prophylactic agent against HAPE. By conducting a parallel-group double blind, randomized, placebo-controlled trial, we investigated the effect of chronic sildenafil administration on pulmonary artery systolic pressure (PASP) and symptoms of acute mountain sickness (AMS) during acclimatization to high altitude. Sixty-two healthy lowland volunteers (36 male; median age 21 years, range 18 to 31) on the Apex 2 research expedition were flown to La Paz, Bolivia (3650 m), and after 4-5 days acclimatization ascended over 90 min to 5200 m. The treatment group (n=20) received 50 mg sildenafil citrate three times daily. PASP was recorded by echocardiography at sea level and within 6 h, 3 days, and 1 week at 5200 m. AMS was assessed daily using the Lake Louise Consensus symptom score. On intention-to-treat analysis, there was no significant difference in PASP at 5200 m between sildenafil and placebo groups. Median AMS score on Day 2 at 5200 m was significantly higher in the sildenafil group (placebo 4.0, sildenafil 6.5; p=0.004) but there was no difference in prevalence of AMS between groups. Sildenafil administration did not affect PASP in healthy lowland subjects at 5200 m but AMS was significantly more severe on Day 2 at 5200 m with sildenafil. Our data do not support routine prophylactic use of sildenafil to reduce PASP at high altitude in healthy subjects with no history of HAPE. TRIALS REGISTRATION NUMBER: NCT00627965.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether implantable cardioverter defibrillators (ICD) improve survival in patients with severe left ventricular systolic dysfunction (LVSD) after coronary artery bypass graft (CABG) surgery. ICDs are designed to terminate potentially fatal cardiac tachyarrhythmias. A right ventricular lead is mandatory for detection, pacing and defibrillation capabilities. Dual chamber ICDs have an additional right atrial lead and are used for patients with conventional atrioventricular pacing indications. More sophisticated, biventricular devices exist to provide cardiac resynchronisation therapy (CRT) in addition to defibrillation (CRT-D). ICDs have been extensively investigated in patients with LVSD post myocardial infarction and in patients with non-ischaemic cardiomyopathy for both secondary prevention (history of ventricular arrhythmias) and primary prevention (deemed high risk for ventricular arrhythmias). This best evidence topic aims to review the evidence and its applicability to patients post CABG. Nine hundred and sixteen papers were identified using the search method outlined. Eight randomised controlled trials, two meta-analyses, and one non-randomised trial, in addition to international guidelines presented the best evidence to answer the clinical question. The current evidence base and guidelines suggest that ICDs should be considered for all patients with LVSD [ejection fraction (EF) ≤30-40%] receiving optimal pharmacological management, who are ≥40 days post MI [four weeks for National Institute for Health and Clinical Excellence (NICE)] and in New York Heart Association (NYHA) class I-III. UK NICE guidelines require in addition; non-sustained ventricular tachycardia (NSVT) on a Holter monitor and inducible ventricular tachycardia at electrophysiological study for EF between 30 and 35%; or a QRS120 ms if EF30%. The North American guidelines recommend EF30% as a threshold for those with NYHA class I symptoms. The evidence is applicable to patients post CABG, provided all the other criteria are met. European Society of Cardiology (ESC) guidelines recommend waiting at least three months (consensus opinion) after revascularisation prior to assessment for an ICD, to allow time for potential recovery of ventricular function.

Acute mountain sickness may be caused by cerebrovascular fluid leakage due to oxidative damage to the endothelium. This may be reduced by oral antioxidant supplementation.To assess the effectiveness of antioxidant supplementation for the prevention of acute mountain sickness (AMS).A parallel-group double blind, randomized placebo-controlled trial.The study was conducted in a university clinical research facility and a high altitude research laboratory. Eighty-three healthy lowland volunteers ascended to 5200 m on the Apex 2 high altitude research expedition. The treatment group received a daily dose of 1 g l-ascorbic acid, 400 IU of alpha-tocopherol acetate and 600 mg of alpha-lipoic acid (Cultech Ltd., Wales, UK) in four divided doses. Prevalence of AMS was measured using the Lake Louise Consensus score sheet (LLS). Secondary outcomes were AMS severity measured using a novel visual analogue scale, arterial oxygen saturation and pulmonary artery systolic pressure (PASP).Forty-one subjects were allocated to the antioxidant group, and 42 to the placebo group. There was no difference in AMS incidence or severity between the antioxidant and placebo groups using the LLS at any time at high altitude. At the pre-determined comparison point at Day 2 at 5200 m, 69% of the antioxidant group (25/36) and 66% of the placebo group (23/35) had AMS using the LLS criteria (P = 0.74). No differences were observed between the groups for PASP, oxygen saturation, presence of a pericardial effusion or AMS assessed by VAS.This trial found no evidence of benefit from antioxidant supplementation at high altitude.NCT00664001.

SummaryVentilatory control undergoes profound changes on ascent to high altitude. We hypothesized that the fall in citric acid cough threshold seen on ascent to altitude is mediated by changes in the central control of cough and would parallel changes in central ventilatory control assessed by the hypercapnic ventilatory response (HCVR). Twenty-five healthy volunteers underwent measurements of HCVR and citric acid sensitivity at sea level and during a 9 day sojourn at 5200m. None of the subjects had any evidence of respiratory infection. Citric acid cough threshold fell significantly on ascent to 5200m. The slope, S, of the HCVR increased significantly on ascent to 5200m and during the stay at altitude. There was no correlation between citric acid sensitivity and HCVR. We conclude that the change in citric acid cough threshold seen on exposure to hypobaric hypoxia is unlikely to be mediated by changes in the central control of cough. Sensitivity to citric acid may be due to early subclinical pulmonary edema stimulating airway sensory nerve endings.

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

Background Cardiomyopathy is an independent predictor of morbidity and early mortality in mitochondrial DNA disease, and occurs in 20%–40% of adult patients harbouring the common m.3243A>G mutation, usually with a hypertrophic phenotype. Pathogenetic mechanisms are unclear yet no detailed study of myocardial structure, function and bioenergetics has been performed in m.3243A>G mutation carriers to identify early markers of cardiac involvement. Methods Cardiac MRI was performed in 20 adult patients (10 males, mean age 38.7±13.1 years) harbouring the m.3243A>G mutation, without clinical evidence of cardiac involvement on routine ECG and echocardiographic screening, and 20 age- and gender-matched healthy controls (10 males, 38.4±14.2 years): (1) phosphorus-31 magnetic resonance spectroscopy, (2) cine imaging (3), cardiac tagging, and (4) late gadolinium enhancement (LGE) imaging on a Philips Intera Achieva 3 Tesla scanner. Clinical disease burden was determined using: (1) the Newcastle Mitochondrial Disease Adult Scale (NMDAS), a 29-domain validated scoring system with a single cardiac domain, and (2) urinary mutation load, the best predictor of overall clinical outcome in m.3243A>G mutation carriers. Results Compared to control subjects and following Bonferroni correction for multiple comparisons, patients had increased left ventricular mass index (LVMI), LV mass to end-diastolic volume ratio (M/V ratio), LV radial wall thicknesses (all p Conclusions Concentric remodelling and subendocardial dysfunction are prevalent in m.3243A>G mutation carriers without clinical cardiac disease. Assessment of myocardial deformation may be useful in monitoring disease progression or response to early intervention. Patients with higher urinary mutation loads and disease burden may be at increased risk of cardiac involvement.

Aims Respiratory chain abnormalities have been documented in children with idiopathic cardiomyopathy undergoing diagnostic endomyocardial biopsy.1 Mitochondrial disease can present with isolated cardiomyopathy or prominent cardiac involvement in multisystem disease, but when present, the cardiac phenotype is often severe.2 We undertook a prospective study to assess the frequency and characteristics of mitochondrial disease in children undergoing orthotopic cardiac transplantation or implantation of ventricular assist device (VAD) for severe cardiomyopathy. Methods Macrobiopsies from the left ventricle±paired skeletal muscle were obtained from consecutive children Results 30 patients (14 male) underwent first cardiac transplantation±VAD implantation, with a further four patients (1 male) undergoing VAD implantation only (overall mean age 5.9±1.0 years). Myocardial macrobiopsies were available from 71% (24/34) of patients with paired skeletal muscle samples in seven patients. Histochemical and biochemical analyses of cardiac muscle were abnormal in 13% (3/24) of patients. Sequential COX/SDH histochemistry revealed a mosaic pattern of COX-deficiency within the myocardium of two patients. Respiratory chain activities were abnormal in cardiac muscle homogenates from both patients, while abnormalities were also detected in a third patient who had normal histochemistry. Molecular genetic testing is ongoing, but no pathogenic mtDNA mutations were identified in patients with histochemical abnormalities. Conclusion Mitochondrial disease is common in children with severe cardiomyopathy, and may present as isolated cardiomyopathy or multisystem disease, yet the diagnosis was considered prior to myocardial tissue analysis in only one patient in this study. Given the potential tissue-specific nature of mitochondrial disease, investigation of myocardial tissue should be considered in all children with cardiomyopathy undergoing invasive cardiac procedures.

A 59-year-old woman with hypertension and previously well-controlled angina presented with acute central chest pain. ECG confirmed an inferior ST-segment elevation myocardial infarction. Emergency coronary angiography revealed severe stenosis of the right coronary artery in the mid-vessel with large thrombus burden (figure 1). Consistent with current clinical guidelines, manual thrombus aspiration using an Export® device (Medtronic, USA) was attempted but there …