Outcomes of Atrioventricular Node Ablation and Pacing in Patients with Heart Failure and Atrial Fibrillation: From Cardiac Resynchronization Therapy to His Bundle Pacing.

Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: APubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that the "pace and ablate" strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding pacemaker implantation, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle branch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and pacemaker implantation is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

Complication rates following ventricular tachycardia ablation in ischaemic and non-ischaemic cardiomyopathies: a systematic review.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is associated with potential major complications, including mortality. The risk of acute complications in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) has not been systematically evaluated. METHODS: PubMed was searched for studies of catheter ablation of VT published between September 2009 and September 2019. Pre-specified primary outcomes were (1) rate of major acute complications, including death, and (2) mortality rate. RESULTS: A total of 7395 references were evaluated for relevance. From this, 50 studies with a total of 3833 patients undergoing 4319 VT ablation procedures fulfilled the inclusion criteria (mean age 59 years; male 82%; 2363 [62%] ICM; 1470 [38%] NICM). The overall major complication rate in ICM cohorts was 9.4% (95% CI, 8.1-10.7) and NICM cohorts was 7.1% (95% CI, 6.0-8.3). Reported complication rates were highly variable between studies (ICM I2 = 90%; NICM I2 = 89%). Vascular complications (ICM 2.5% [95% CI, 1.9-3.1]; NICM 1.2% [95% CI, 0.7-1.7]) and cerebrovascular events (ICM 0.5% [95% CI, 0.2-0.7]; NICM, 0.1% [95% CI, 0-0.2]) were significantly higher in ICM cohorts. Acute mortality rates in the ICM and NICM cohorts were low (ICM 0.9% [95% CI, 0.5-1.3]; NICM 0.6% [95% CI, 0.3-1.0]) with the majority of overall deaths (ICM 75%; NICM 80%) due to either recurrent VT or cardiogenic shock. CONCLUSION: Overall acute complication rates of VT ablation are comparable between ICM and NICM patients. However, the pattern and predictors of complications vary depending on the underlying cardiomyopathy.

The Impact of a Nurse-Led Syncope Clinic: Experience from a single UK tertiary center.

BACKGROUND: Syncope is a leading cause of hospital admission and is associated with significant morbidity and mortality. Our Syncope Clinic commenced in 2014 and we sought to evaluate its impact on outcomes (1-yr mortality and syncope re-hospitalization) in patients discharged following syncope admission. METHODS: A single-center study of all consecutive patients discharged with syncope (ICD-10 R55) between April 2012 and 2017. Patient demographics, comorbidities, hospital stay, syncope re-hospitalization, and mortality at one-year were collected. Those subsequently referred and seen in Syncope Clinic were compared with those who were not and predictors of poor outcome were evaluated. RESULTS: In total 2950 patients were discharged from hospital with syncope (median age: 73years, 51% male) with 1220 (41%) discharged same-day; after commencement of Syncope Clinic 231were subsequently reviewed here. Overall mortality was 11%, which was lower in the Syncope Clinic group (3% vs 12%, P < .001). Temporal analysis revealed reduced re-hospitalization following commencement of Syncope Clinic (2% vs 6%, P = .027). Independent predictors of mortality were increasing age (HR 1.03, 95% CI 1.03-1.04), AF (HR 1.6, 95% CI 1.2-2.1), HF (HR 2.2, 95% CI 1.6-3.0), COPD (HR 1.9, 95% CI 1.4-2.7), and CHADS2 score ≥ 1 (HR 1.45, 95% CI 1,12-1.87). Syncope Clinic attendance was associated with reduced mortality (HR 0.3, 95% CI 0.1-0.6). CONCLUSIONS: Syncope patients discharged from hospital had reduced 1yr mortality if seen in subsequent Syncope Clinic. Independent predictors of mortality were COPD, HF, AF, and CHADS2 ≥1. Prospective randomized trials of Syncope Clinics are warranted.

SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know.

There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.

Impact of COVID-19 on primary percutaneous coronary intervention centres in the UK: a survey.

During the coronavirus disease (COVID-19) pandemic, the British Cardiovascular Society/British Cardiovascular Intervention Society and the British Heart Rhythm Society recommended to postpone non-urgent elective work and that primary percutaneous coronary intervention (PCI) should remain the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of COVID-19 on the primary PCI service within the United Kingdom (UK). A survey of 43 UK primary PCI centres was performed and a significant reduction in the number of cath labs open was found (pre-COVID 3.6±1.8 vs. post-COVID 2.1±0.8; p<0.001) with only 64% of cath labs remained open during the COVID-19 pandemic. Primary PCI remained first-line treatment for STEMI in all centres surveyed.

Enhanced ventricular tachycardia substrate resolution with a novel omnipolar high-density mapping catheter: the omnimapping study.

BACKGROUND: Defining diastolic slow-conduction channels within the borderzone (BZ) of scar-dependent re-entrant ventricular tachycardia (VT) is key for effective mapping and ablation strategies. Understanding wavefront propagation is driving advances in high-density (HD) mapping. The newly developed Advisor™ HD Grid Mapping Catheter (HD GRID) has equidistant spacing of 16, 1 mm electrodes in a 4 × 4 3 mm interspaced arrangement allowing bipolar recordings along and uniquely across the splines (orthogonal vector) to facilitate substrate mapping in a WAVE configuration (WAVE). The purpose of this study was to determine the relative importance of the WAVE configuration compared to the STANDARD linear-only bipolar configuration (STANDARD) in defining VT substrate. METHODS: Thirteen patients underwent VT ablation at our institution. In all cases, a substrate map was constructed with the HD GRID in the WAVE configuration (conWAVE) to guide ablation strategy. At the end of the procedure, the voltage map was remapped in the STANDARD configuration (conSTANDARD) using the turbo-map function. Detailed post-hoc analysis of the WAVE and STANDARD maps was performed blinded to the configuration. Quantification of total scar area, BZ and dense scar area with assessment of conduction channels (CC) was performed. RESULTS: The substrate maps conSTANDARD vs conWAVE showed statistically significant differences in the total scar area (56 ± 32 cm2 vs 51 ± 30 cm2; p = 0.035), dense scar area (36 ± 25 cm2 vs 29 ± 22 cm2; p = 0.002) and number of CC (3.3 ± 1.6 vs 4.8 ± 2.5; p = 0.026). conWAVE collected more points than the conSTANDARD settings (p = 0.001); however, it used fewer points in map construction (p = 0.023). CONCLUSIONS: The multipolar Advisor™ HD Grid Mapping Catheter in conWAVE provides more efficient point acquisition and greater VT substrate definition of the borderzone particularly at the low-voltage range compared to conSTANDARD. This greater resolution within the low-voltage range facilitated CC definition and quantification within the scar, which is essential in guiding the ablation strategy.

Long-term follow-up of normal and structural heart ventricular tachycardia catheter ablation: real-world experience from a UK tertiary centre.

Background: Ventricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures. Objective: To evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting. Methods: This is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (>3 episodes within 24 hours) or appropriate shock. Results: Forty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were male, 81% were Caucasian and 66% were elective cases. The aetiology of VT included normal heart (49%), ischaemic cardiomyopathy (ICM, 36%), dilated cardiomyopathy (9%), hypertrophic cardiomyopathy (4%) and valvular heart disease (2%). Procedural success occurred in 83%, with six major complications. After a median follow-up of 231 days (lower quartile 133, upper quartile 631), the primary outcome occurred in 28% of patients. There were two non-arrhythmic deaths (4%). At a median follow-up of 193 days (129-468), the primary outcome occurred in 19% of patients with ICM, while VT storm/appropriate shocks occurred in three patients (17%). Conclusions: Our real-world registry confirms that VT ablation is safe, and is associated with high acute procedural success and long-term outcomes comparable with randomised controlled studies.

Retrograde aortic access during ventricular tachycardia ablation: Indications, techniques, and challenges.

The retrograde aortic (RA) route is a widely used access route for mapping and ablation of ventricular tachycardias (VT) arising from the left ventricular endocardium. With the expanding role of VT ablation in patients with significant comorbidity, the choice between the RA and transseptal access routes is an increasingly important consideration. An individualized decision based on the location of the arrhythmogenic substrate, vascular anatomy, aortic valve morphology, and operator experience is necessary when deciding on the optimal access route. Among patients with challenging vascular anatomy, growing experience from structural interventions such as transcatheter aortic valve replacements and peripheral vascular interventions has provided valuable insights into techniques for safe retrograde access. The present review focuses on patient selection for RA access, potential complications associated with the technique, and optimal approaches for access in patients with challenging vascular or aortic valve anatomy.

Acute hydrocortisone administration reduces cardiovagal baroreflex sensitivity and heart rate variability in young men.

KEY POINTS: A surge in cortisol during acute physiological and pathophysiological stress may precipitate ventricular arrhythmia and myocardial infarction. Reduced cardiovagal baroreflex sensitivity and heart rate variability are observed during acute stress and are associated with an increased risk of acute cardiac events. In the present study, healthy young men received either a single iv bolus of saline (placebo) or hydrocortisone, 1 week apart, in accordance with a randomized, placebo-controlled, cross-over study design. Hydrocortisone acutely increased heart rate and blood pressure and reduced cardiovagal baroreflex sensitivity and heart rate variability in young men. These findings suggest that, by reducing cardiovagal baroreflex sensitivity and heart rate variability, acute surges in cortisol facilitate a pro-arrhythmic milieu and provide an important mechanistic link between stress and acute cardiac events ABSTRACT: Surges in cortisol concentration during acute stress may increase cardiovascular risk. To better understand the interactions between cortisol and the autonomic nervous system, we determined the acute effects of hydrocortisone administration on cardiovagal baroreflex sensitivity (BRS), heart rate variability (HRV) and cardiovascular reactivity. In a randomized, placebo-controlled, single-blinded cross-over study, 10 healthy males received either a single iv bolus of saline (placebo) or 200 mg of hydrocortisone, 1 week apart. Heart rate (HR), blood pressure (BP) and limb blood flow were monitored 3 h later, at rest and during the sequential infusion of sodium nitroprusside and phenylephrine (modified Oxford Technique), a cold pressor test and a mental arithmetic stress task. HRV was assessed using the square root of the mean of the sum of the squares of differences between successive R-R intervals (rMSSD). Hydrocortisone markedly increased serum cortisol 3 h following infusion and also compared to placebo. In addition, hydrocortisone elevated resting HR (+7 ± 4 beats min-1 ; P < 0.001) and systolic BP (+5 ± 5 mmHg; P = 0.008); lowered cardiovagal BRS [geometric mean (95% confidence interval) 15.6 (11.1-22.1) ms/mmHg vs. 26.2 (17.4--39.5) ms/mmHg, P = 0.011] and HRV (rMSSD 59 ± 29 ms vs. 84 ± 38 ms, P = 0.004) and increased leg vasoconstrictor responses to cold pressor test (Δ leg vascular conductance -45 ± 20% vs. -23 ± 26%; P = 0.023). In young men, an acute cortisol surge is accompanied by increases in HR and BP, as well as reductions in cardiovagal BRS and HRV, potentially providing a pro-arrhythmic milieu that may precipitate ventricular arrhythmia or myocardial infarction and increase cardiovascular risk.

Cardiovascular autonomic regulation, inflammation and pain in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by reduced heart rate variability (HRV) of unknown cause. We tested the hypothesis that low HRV, indicative of cardiac autonomic cardiovascular dysfunction, was associated with systemic inflammation and pain. Given the high prevalence of hypertension (HTN) in RA, a condition itself associated with low HRV, we also assessed whether the presence of hypertension further reduced HRV in RA. METHODS: In RA-normotensive (n=13), RA-HTN (n=17), normotensive controls (NC; n=17) and HTN (n=16) controls, blood pressure and heart rate were recorded. Time and frequency domain measures of HRV along with serological markers of inflammation (high sensitivity C-reactive protein [hs-CRP], tumour necrosis factor-α [TNF-α] and interleukins [IL]) were determined. Reported pain was assessed using a visual analogue scale. RESULTS: Time (rMSSD, pNN50%) and frequency (high frequency power, low frequency power, total power) domain measures of HRV were lower in the RA, RA-HTN and HTN groups, compared to NC (p=0.001). However, no significant differences in HRV were noted between the RA, RA-HTN and HTN groups. Inverse associations were found between time and frequency measures of HRV and inflammatory cytokines (IL-6 and IL-10), but were not independent after multivariable analysis. hs-CRP and pain were independently and inversely associated with time domain (rMMSD, pNN50%) parameters of HRV. CONCLUSIONS: These findings suggest that lower HRV is associated with increased inflammation and independently associated with increased reported pain, but not compounded by the presence of HTN in patients with RA.

Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults.

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis.

KEY POINTS: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known. In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls. Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity. The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min-1 ) compared to NC (22 ± 9 bursts min-1 ; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients [5(3-8), 4 (2-7), 6 (4-9) ms mmHg-1 ] compared to NC [11 (8-15) ms mmHg-1 ; P = 0.002]. HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events.

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

BACKGROUND: Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. PURPOSE: To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. METHODS: Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. RESULTS: Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. CONCLUSIONS: HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Association between corrected QT interval and inflammatory cytokines in rheumatoid arthritis.

OBJECTIVE: Corrected QT (QTc) interval predicts all-cause and cardiovascular mortality and may contribute to the increased mortality risk in rheumatoid arthritis (RA). Animal experiments have shown that proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 1 (IL-1)] can prolong cardiomyocyte action potential. We sought to determine whether elevations in circulating inflammatory cytokines were independently associated with QTc prolongation in patients with RA. METHODS: One hundred twelve patients [median age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA cohort underwent baseline 12-lead electrocardiograms for QT interval measurement and contemporary blood sampling to assess concentrations of inflammatory markers including C-reactive protein (CRP), TNF-α, and interleukins (IL-1α, IL-1ß, IL-6, IL-10). QTc was calculated using the Bazett (QTBAZ = QT ÷ √RR) and Framingham Heart Study (QTFHS = QT + 0.154 × [1 - RR]) heart rate correction formulas. RESULTS: Inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-10) were positively correlated with QTBAZ (Spearman rank correlation coefficient rho = 0.199, 0.210, 0.222, 0.333; all p < 0.05). In multivariable regression analysis, these associations were all confounded by age except IL-10, where higher tertile groups were independently and positively associated with QTBAZ (ß = 0.202, p = 0.023) and QTFHS (ß = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with QTBAZ (ß = 0.278, p = 0.001), but not QTFHS. CONCLUSION: To our knowledge, ours is the first study demonstrating a contemporary link between inflammatory cytokines and QT interval in humans. Our results suggest that a lower inflammatory burden may protect against QTc prolongation in patients with RA. However, further studies are required to confirm the effects of pro- and antiinflammatory cytokines on QTc interval.

Autonomic function and rheumatoid arthritis: a systematic review.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory condition with increased all-cause and cardiovascular mortality. Accumulating evidence indicates that the immune and autonomic nervous systems (ANS) are major contributors to the pathogenesis of cardiovascular disease. We performed the first systematic literature review to determine the prevalence and nature of ANS dysfunction in RA and whether there is a causal relationship between inflammation and ANS function. METHODS: Electronic databases (MEDLINE, Central and Cochrane Library) were searched for studies of RA patients where autonomic function was assessed. RESULTS: A total of 40 studies were included. ANS function was assessed by clinical cardiovascular reflex tests (CCTs) (n = 18), heart rate variability (HRV) (n = 15), catecholamines (n = 5), biomarkers of sympathetic activity (n = 5), sympathetic skin responses (n = 5), cardiac baroreflex sensitivity (cBRS) (n = 2) and pupillary light reflexes (n = 2). A prevalence of ~60% (median, range: 20-86%) of ANS dysfunction (defined by abnormal CCTs) in RA was reported in 9 small studies. Overall, 73% of studies (n = 27/37) reported at least one of the following abnormalities in ANS function: parasympathetic dysfunction (n = 20/26, 77%), sympathetic dysfunction (n = 16/30, 53%) or reduced cBRS (n = 1/2, 50%). An association between increased inflammation and ANS dysfunction was found (n = 7/19, 37%), although causal relationships could not be elucidated from the studies available to date. CONCLUSIONS: ANS dysfunction is prevalent in ~60% of RA patients. The main pattern of dysfunction is impairment of cardiovascular reflexes and altered HRV, indicative of reduced cardiac parasympathetic (strong evidence) activity and elevated cardiac sympathetic activity (limited evidence). The literature to date is underpowered to determine causal relationships between inflammation and ANS dysfunction in RA.

Muscle metaboreflex and autonomic regulation of heart rate in humans.

We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), ß1-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR increased with partial flow restriction during leg cycling in the control condition (11 ± 2 beats min(-1); P < 0.05). The magnitude of this increase in HR was similar with parasympathetic blockade (11 ± 2 beats min(-1)), but attenuated with ß-adrenergic blockade (4 ± 1 beats min(-1); P < 0.05 vs. control and parasympathetic blockade). During PEI following leg cycling exercise, HR remained similarly elevated above rest under all conditions (11 ± 2, 13 ± 3 and 9 ± 4 beats min(-1), for control, ß-adrenergic and parasympathetic blockade; P > 0.05 between conditions). During PEI following handgrip, HR was similarly elevated from rest under control and parasympathetic blockade (4 ± 1 vs. 4 ± 2 beats min(-1); P > 0.05 between conditions) conditions, but attenuated with ß-adrenergic blockade (0.2 ± 1 beats min(-1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg cycling) is there a contribution from the partial withdrawal of cardiac parasympathetic tone.

Benefit-risk assessment of dronedarone in the treatment of atrial fibrillation.

Rhythm control in atrial fibrillation (AF) can be achieved using pharmacological therapy. Amiodarone is the most efficacious anti-arrhythmic agent; however, its use is limited due to an unfavourable safety profile, including pro-arrhythmia, thyroid, liver, skin and pulmonary complications. Dronedarone, which is structurally similar to amiodarone, was developed to try and achieve a favourable balance of efficacy and risk. Dronedarone has been evaluated in several large clinical trials, which have shown reduced mortality and hospitalization rates in patients with non-permanent AF. In patients with permanent AF and/or heart failure, dronedarone has been shown to cause increased mortality and morbidity and should not be used in these groups. Compared with amiodarone, dronedarone has fewer toxic effects (thyroid, skin, pulmonary) and, although less efficacious, may be used as first-line therapy for maintenance of sinus rhythm in patients with non-permanent AF. Clinicians must be vigilant in monitoring their patients to ensure they do not develop permanent AF or heart failure.