Deglutition-Induced Atrial Tachycardia Localised with Contact Force-Guided Activation Mapping.

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.

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial.

BACKGROUND: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. METHODS: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence > 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications. RESULTS: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43-2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29-0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). CONCLUSION: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF.

Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management.

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.

Cryoballoon Pulmonary Vein Isolation as First-Line Treatment for Typical Atrial Flutter.

OBJECTIVE: We aimed to compare cryoballoon pulmonary vein isolation (PVI) with standard radiofrequency cavotricuspid isthmus (CTI) ablation as first-line treatment for typical atrial flutter (AFL). METHODS: Cryoballoon Pulmonary Vein Isolation as First-Line Treatment for Typical Atrial Flutter was an international, multicentre, open with blinded assessment trial. Patients with CTI-dependent AFL and no documented atrial fibrillation (AF) were randomised to either cryoballoon PVI alone or radiofrequency CTI ablation. Primary efficacy outcome was time to first recurrence of sustained (>30 s) symptomatic atrial arrhythmia (AF/AFL/atrial tachycardia) at 12 months as assessed by continuous monitoring with an implantable loop recorder. Primary safety outcome was a composite of death, stroke, tamponade requiring drainage, atrio-oesophageal fistula, pacemaker implantation, serious vascular complications or persistent phrenic nerve palsy. RESULTS: Trial recruitment was halted at 113 of the target 130 patients because of the SARS-CoV-2 pandemic (PVI, n=59; CTI ablation, n=54). Median age was 66 (IQR 61-71) years, with 98 (86.7%) men. At 12 months, the primary outcome occurred in 11 (18.6%) patients in the PVI group and 9 (16.7%) patients in the CTI group. There was no significant difference in the primary efficacy outcome between the groups (HR 1.11, 95% CI 0.46 to 2.67). AFL recurred in six (10.2%) patients in the PVI arm and one (1.9%) patient in the CTI arm (p=0.116). Time to occurrence of AF of ≥2 min was significantly reduced with cryoballoon PVI (HR 0.46, 95% CI 0.25 to 0.85). The composite safety outcome occurred in four patients in the PVI arm and three patients in the CTI arm (p=1.000). CONCLUSION: Cryoballoon PVI as first-line treatment for AFL is equally effective compared with standard CTI ablation for preventing recurrence of atrial arrhythmia and better at preventing new-onset AF. TRIAL REGISTRATION NUMBER: NCT03401099.

Arrhythmia prevalence and sudden death risk in adults with the m.3243A>G mitochondrial disorder.

AIMS: To define the prevalence of non-sustained tachyarrhythmias and bradyarrhythmias in patients with the m.3243A>G mitochondrial genotype and a previously defined, profile, associated with 'high sudden-death risk'. METHODS AND RESULTS: Patients at high risk of sudden death because of combinations of ventricular hypertrophy, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes family phenotype, epilepsy or high mutation load, due to the m.3243A>G mutation, were identified from a mitochondrial cohort of 209 patients. All recruited had serial ECG and echo assessments previously according to schedule, had an ECG-loop recorder implanted and were followed for as long as the device allowed. Devices were programmed to detect non-sustained brady- or tachy-arrhythmias. This provided comprehensive rhythm surveillance and automatic downloads of all detections to a monitoring station for cardiology interpretation. Those with sinus tachycardia were treated with beta-blockers and those with ventricular hypertrophy received a beta-blocker and ACE-inhibitor combination.Nine consecutive patients, approached (37.2±3.9 years, seven males) and consented, were recruited. None died and no arrhythmias longer than 30s duration occurred during 3-year follow-up. Three patients reported palpitations but ECGs correlated with sinus rhythm. One manifest physiological, sinus pauses >3.5 s during sleep and another had one asymptomatic episode of non-sustained ventricular tachycardia. CONCLUSIONS: Despite 'high-risk' features for sudden death, those studied had negligible prevalence of arrhythmias over prolonged follow-up. By implication, the myocardium in this genotype is not primarily arrhythmogenic. Arrhythmias may not explain sudden death in patients without Wolff-Parkinson-White or abnormal atrioventricular conduction or, it must require a confluence of other, dynamic, proarrhythmic factors to trigger them.

Prediction of incident atrial fibrillation in community-based electronic health records: a systematic review with meta-analysis.

OBJECTIVE: Atrial fibrillation (AF) is common and is associated with an increased risk of stroke. We aimed to systematically review and meta-analyse multivariable prediction models derived and/or validated in electronic health records (EHRs) and/or administrative claims databases for the prediction of incident AF in the community. METHODS: Ovid Medline and Ovid Embase were searched for records from inception to 23 March 2021. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: Eleven studies met inclusion criteria, describing nine prediction models, with four eligible for meta-analysis including 9 289 959 patients. The CHADS (Congestive heart failure, Hypertension, Age>75, Diabetes mellitus, prior Stroke or transient ischemic attack) (summary c-statistic 0.674; 95% CI 0.610 to 0.732; 95% PI 0.526-0.815), CHA2DS2-VASc (Congestive heart failure, Hypertension, Age>75 (2 points), Stroke/transient ischemic attack/thromboembolism (2 points), Vascular disease, Age 65-74, Sex category) (summary c-statistic 0.679; 95% CI 0.620 to 0.736; 95% PI 0.531-0.811) and HATCH (Hypertension, Age, stroke or Transient ischemic attack, Chronic obstructive pulmonary disease, Heart failure) (summary c-statistic 0.669; 95% CI 0.600 to 0.732; 95% PI 0.513-0.803) models resulted in a c-statistic with a statistically significant 95% PI and moderate discriminative performance. No model met eligibility for inclusion in meta-analysis if studies at high risk of bias were excluded and certainty of effect estimates was 'low'. Models derived by machine learning demonstrated strong discriminative performance, but lacked rigorous external validation. CONCLUSIONS: Models externally validated for prediction of incident AF in community-based EHR demonstrate moderate predictive ability and high risk of bias. Novel methods may provide stronger discriminative performance. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021245093.

A Novel Quadripolar Active Fixation Left-Ventricular Pacing Lead for Cardiac Resynchronization Therapy: Initial United Kingdom Experience.

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.

The use of a single chamber leadless pacemaker for the treatment of cardioinhibitory vasovagal syncope.

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 ±â€¯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 ±â€¯8 yrs. with an average frequency of syncope being 4 ±â€¯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 ±â€¯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.

Phosphodiesterase type 5 inhibitors in the treatment and prevention of high altitude pulmonary edema.

The combination of a tendency to affect otherwise fit and healthy individuals, and a characteristically rapid progression to death within hours of the first symptoms, renders high altitude pulmonary edema (HAPE) a particularly devastating illness in travelers to high altitudes. The alveolar edema and ventilation:perfusion mismatch initiate a catastrophic downward spiral of worsening alveolar hypoxia. This reviewo discusses the rationale for the use of phosphodiesterase (PDE)5 inhibitors in HAPE, compares the pharmacokinetic properties of the available agents, and appraises the relevant experimental evidence. Although this class of drugs shows promise in high altitude medicine, further research is necessary to determine the efficacy and safety of PDE5 inhibitors as a treatment for established

Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude.

BACKGROUND: 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. METHODS: 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). RESULTS: On ascent, F2-isoprostane levels were significantly elevated compared with those at sea level (p < 0.01). After 1 week at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and serum urate concentration were significantly elevated (each p < 0.01 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). CONCLUSIONS: Our results support the hypothesis that urate may act as a responsive endogenous antioxidant in high-altitude hypoxia.

Age-related decline in cardiac autonomic function is not attenuated with increased physical activity.

Age and physical inactivity are important risk factors for cardiovascular mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR), measures of cardiac autonomic function, are strong predictors of mortality. The present study defined the effect of age and physical activity on HRRE and HRR. Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50 years; and older, 65-81 years) and daily physical activity (low active <7500, high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test. The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes of exercise and at 1/3 of total exercise time, and HRR as the difference in heart rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with a significant decline in HRRE at 1 min and 1/3 of exercise time (r=-0.27, p=0.04, and r=-0.39, p=0.02) and HRR at 2 min and 3 min (r=-0.35, p=0.01, and r=-0.31, p=0.02). There was no significant difference in HRRE and HRR between high and low-active middle-age and older women (p>0.05). Increased level of habitual physical activity level appears to have a limited effect on age-related decline in cardiac autonomic function in women.

Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure.

Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown. We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium.

Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

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.

Video-assisted thoracoscopic left ventricular pacing in patients with and without previous sternotomy.

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.

Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I.

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.

Concentric hypertrophic remodelling and subendocardial dysfunction in mitochondrial DNA point mutation carriers.

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.

Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease.

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<0.05) and LV mass to end-diastolic volume ratio, and decreased longitudinal shortening and myocardial phosphocreatine/adenosine triphosphate ratio (all p<0.01). Peak arterial-venous oxygen difference (p<0.05), oxygen uptake (VO2) and power were decreased in patients (both p<0.01) with no significant difference in cardiac power output. All patients remained stable and completed ≥80% sessions. With training, there were similar proportional increases in peak VO2, anaerobic threshold and work capacity in patients and controls. LVMI increased in both groups (p<0.01), with no significant effect on myocardial function or bioenergetics. Pre- and post-exercise training, HRV and BPV demonstrated increased low frequency and decreased high frequency components in patients compared to controls (all p<0.05). CONCLUSION: Patients with mitochondrial disease and controls achieved similar proportional benefits of exercise training, without evidence of disease progression, or deleterious effects on cardiac function. Reduced exercise capacity is largely mediated through skeletal muscle dysfunction at baseline and sympathetic over-activation may be important in pathogenesis.

Cardiac torsion-strain relationships in fatigued primary biliary cirrhosis patients show accelerated aging: a pilot cross-sectional study.

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.

In patients undergoing aortic valve replacement, what factors predict the requirement for permanent pacemaker implantation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question was to determine what preoperative, perioperative and postoperative factors influence the requirement for permanent pacemaker (PPM) implantation postisolated aortic valve replacement (AVR). Transcatheter aortic valve intervention was not included in this analysis. Using the reported search method outlined below, 705 papers were found. No randomised controlled trials, meta-analyses or registries were identified. Seven single-centre retrospective observational studies represent the best evidence on the subject. The author, journal, date and country of publication, level of evidence, patient group studied, study type, outcomes and results were tabulated. The incidence of PPM implantation following AVR varied from 3.0% to 11.8% (mean 7.0%, median 7.2%). Current best available evidence suggests that baseline evidence of conducting system disease - first degree atrioventricular block (AVB), left anterior hemiblock, right bundle branch block (RBBB) or left bundle branch block (LBBB) is the most powerful independent predictor of PPM requirement following AVR. Other important predictors are surgery for aortic regurgitation, preoperative myocardial infarction and longer perioperative cardiopulmonary bypass time. No consistent postoperative factors were identified. The mean time to PPM implant postAVR ranged from 6 to 13 days in the four studies that reported it. Current European Society of Cardiology guidelines recommend a period of seven days of persistent AVB postsurgery prior to PPM implantation.