A comprehensive protocol combining in vivo and ex vivo electrophysiological experiments in an arrhythmogenic animal model.

Ventricular arrhythmias contribute significantly to cardiovascular mortality, with coronary artery disease as the predominant underlying cause. Understanding the mechanisms of arrhythmogenesis is essential to identify proarrhythmic factors and develop novel approaches for antiarrhythmic prophylaxis and treatment. Animal models are vital in basic research on cardiac arrhythmias, encompassing molecular, cellular, ex vivo whole heart, and in vivo models. Most studies use either in vivo protocols lacking important information on clinical relevance or exclusively ex vivo protocols, thereby missing the opportunity to explore underlying mechanisms. Consequently, interpretation may be difficult due to dissimilarities in animal models, interventions, and individual properties across animals. Moreover, proarrhythmic effects observed in vivo are often not replicated in corresponding ex vivo preparations during mechanistic studies. We have established a protocol to perform both an in vivo and ex vivo electrophysiological characterization in an arrhythmogenic rat model with heart failure following myocardial infarction. The same animal is followed throughout the experiment. In vivo methods involve intracardiac programmed electrical stimulation and external defibrillation to terminate sustained ventricular arrhythmia. Ex vivo methods conducted on the Langendorff-perfused heart include an electrophysiological study with optical mapping of regional action potentials, conduction velocities, and dispersion of electrophysiological properties. By exploring the retention of the in vivo proarrhythmic phenotype ex vivo, we aim to examine whether the subsequent ex vivo detailed measurements are relevant to in vivo pathological behavior. This protocol can enhance greater understanding of cardiac arrhythmias by providing a standardized, yet adaptable model for evaluating arrhythmogenicity or antiarrhythmic interventions in cardiac diseases.NEW & NOTEWORTHY Rodent models are widely used in arrhythmia research. However, most studies do not standardize clinically relevant in vivo and ex vivo techniques to support their conclusions. Here, we present a comprehensive electrophysiological protocol in an arrhythmogenic rat model, connecting in vivo and ex vivo programmed electrical stimulation with optical mapping. By establishing this protocol, we aim to facilitate the adoption of a standardized model for investigating arrhythmias, enhancing research rigor and comparability in this field.

Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial.

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.Objectives: To determine the effect of continuous positive airway pressure (CPAP) on AF burden.Methods: This open-label, parallel-group, randomized controlled trial included patients with paroxysmal AF and moderate to severe SA (apnea-hypopnea index ⩾15). A computerized system randomized eligible patients (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n = 55) or usual care alone (control, n = 54). The outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control groups in change of AF burden (percentage of time in AF) as measured by implantable loop recorder.Measurements and Main Results: A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42%) had moderate to severe SA. Of these, 158 (65%) participated in the CPAP run-in period, of whom 39 (25%) patients did not tolerate the treatment. A total of 108 patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last 3 months of CPAP intervention and from 5.0% to 4.3% in the control group. The adjusted between-group difference at follow-up was -0.63 (95% confidence interval, -2.55 to 1.30) percentage points (P = 0.52). Seven serious adverse events (13%) occurred in the CPAP group, and two (4%) occurred in the control group.Conclusions: In patients with paroxysmal AF and SA, treatment with CPAP did not result in a statistically significant reduction in the burden of AF.Clinical trial registered with www.clinicaltrials.gov (NCT02727192).

Comparing manual and automatic scoring of sleep monitoring data from portable polygraphy.

We used sleep monitoring data from a study that investigated the prevalence, characteristics, risk factors and type of sleep apnea (SA) in 579 patients with paroxysmal atrial fibrillation. Most patients were screened for two nights, resulting in 1,043 sleep recordings that each contained data from one night. SA was diagnosed using the Nox T3 portable sleep monitor. An experienced sleep specialist scored the recordings manually using Noxturnal software. A total of 157 women (27%) and 422 men (73%) were examined; 477 (82.7%) had an apnea-hypopnea index (AHI) ≥ 5/hr, whereas moderate to severe SA (AHI ≥ 15/hr) was diagnosed in 243 patients (42.1%). The AHI derived from automatic and manual scoring showed a good agreement (Pearson's r coefficient of 0.96). The median difference in AHI was very small (i.e., 0.72 [mean difference, 1.06]), but was statistically significant (p < .0001). Automatic scoring classified sleep recordings with more than 90% accuracy into SA categories of mild (AHI ≥ 5/hr), moderate (AHI ≥ 15/hr) and severe (AHI ≥ 30/hr). We found a minor (11%-21%) mis-estimation of the number of recordings right above and below the boundary separating mild and moderate SA. The accuracy of automatic scoring differed from recording to recording, especially regarding the sensitivity of detecting disrupted breathing events. We found low to moderate agreement for the duration of disrupted breathing events (r = .53), for which the automatic scoring led to a statistically significant overestimation by 5.22 s (p < .0001).

Implantation of cardioverter-defibrillators at St Olav's Hospital 2006­15. / Implantasjon av hjertestartere ved St. Olavs hospital 2006­15.

BAKGRUNN: Implantasjon av hjertestarter (implantable cardioverter defibrillator, ICD) er etablert behandling hos pasienter med høy risiko for plutselig hjertedød. Studiens formål var å kartlegge pasientkarakteristika, indikasjoner, hyppigheten av ICD-støt, komplikasjoner, reoperasjoner samt endringer over tid i ICD-behandlingen ved St. Olavs hospital. MATERIALE OG METODE: Alle pasienter som fikk implantert hjertestarter ved St. Olavs hospital i perioden 2006-15 ble inkludert. Pasientene ble identifisert i pacemakerregisteret. Data ble hentet fra pacemakerregisteret og elektronisk pasientjournal. RESULTATER: Studien inkluderte 598 pasienter (82 % menn, medianalder 65 år). Tidligere hjertestans eller alvorlig arytmi forelå hos 401 (67 %) av dem som fikk implantert hjertestarter. Koronarsykdom (n = 383) var vanligste underliggende årsak. I oppfølgingstiden (median 3,6 år) fikk 203 (34 %) av pasientene ICD-støt, 154 (26 %) fikk berettigede og 65 (11 %) fikk uberettigede støt. Hos 139 (23 %) pasienter oppstod komplikasjoner. 101 (17 %) pasienter døde i oppfølgingsperioden. FORTOLKNING: Studien gir et godt grunnlag for kvalitetssikring av implantasjonsvirksomheten ved St. Olavs hospital. Kjønns- og aldersfordeling, indikasjon og underliggende årsaker for implantasjon samt hyppighet av støt og komplikasjoner samsvarer godt med tidligere publiserte data.

Treatment of sleep apnea in patients with paroxysmal atrial fibrillation: design and rationale of a randomized controlled trial.

RATIONALE: Atrial fibrillation is associated with increased mortality as well as morbidity. There is strong evidence for an association between atrial fibrillation and sleep apnea. It is not known whether treatment of sleep apnea with continuous positive airway pressure (CPAP) will reduce the burden of atrial fibrillation. OBJECTIVE: The Treatment of Sleep Apnea in Patients with Paroxysmal Atrial Fibrillation study will investigate the effects of CPAP in patients with paroxysmal atrial fibrillation and sleep apnea. DESIGN: The trial has a dual center, randomized, controlled, open-label, parallel design. METHODS: Two centers will enroll a total of 100 patients with both paroxysmal atrial fibrillation and sleep apnea (apnea-hypopnea index [AHI] ≥ 15 events/h) who are scheduled for catheter ablation. Patients will be randomized in a 1:1 ratio to CPAP or control group (50 patients in each arm). The effects of CPAP treatment on atrial fibrillation will be determined using an implanted loop recorder (Reveal LINQ™, Medtronic) that detects all arrhythmia episodes. The primary endpoint is a reduction of the total burden of atrial fibrillation in the intervention group, after 5 months' follow-up (preablation). Reduction in the arrhythmia recurrence rate after ablation is the main secondary endpoint. All patients will be followed up for 12 months after ablation. CONCLUSION: This study is the first randomized controlled trial that will provide data on the effects of CPAP therapy in patients with paroxysmal atrial fibrillation and sleep apnea. The results are expected to improve our understanding of the interaction between paroxysmal atrial fibrillation and sleep apnea. ClinicalTrials.gov Identifier. NCT02727192.

Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction.

Diabetes mellitus (DM) increases the risk of heart failure after myocardial infarction (MI), and aggravates ventricular arrhythmias in heart failure patients. Although exercise training improves cardiac function in heart failure, it is still unclear how it benefits the diabetic heart after MI. To study the effects of aerobic interval training on cardiac function, susceptibility to inducible ventricular arrhythmias and cardiomyocyte calcium handling in DM mice after MI (DM-MI). Male type 2 DM mice (C57BLKS/J Lepr (db) /Lepr (db) ) underwent MI or sham surgery. One group of DM-MI mice was submitted to aerobic interval training running sessions during 6 weeks. Cardiac function and structure were assessed by echocardiography and magnetic resonance imaging, respectively. Ventricular arrhythmias were induced by high-frequency cardiac pacing in vivo. Protein expression was measured by Western blot. DM-MI mice displayed increased susceptibility for inducible ventricular arrhythmias and impaired diastolic function when compared to wild type-MI, which was associated with disruption of cardiomyocyte calcium handling and increased calcium leak from the sarcoplasmic reticulum. High-intensity exercise recovered cardiomyocyte function in vitro, reduced sarcoplasmic reticulum diastolic calcium leak and significantly reduced the incidence of inducible ventricular arrhythmias in vivo in DM-MI mice. Exercise training also normalized the expression profile of key proteins involved in cardiomyocyte calcium handling, suggesting a potential molecular mechanism for the benefits of exercise in DM-MI mice. High-intensity aerobic exercise training recovers cardiomyocyte function and reduces inducible ventricular arrhythmias in infarcted diabetic mice.

Gastroesophageal reflux disease symptoms and risk of atrial fibrillation in a population-based cohort study (the HUNT study).

AIMS: Gastroesophageal reflux disease (GERD) may influence the risk of atrial fibrillation (AF). We investigated the association between symptoms of GERD and AF in the Trøndelag Health Study (HUNT). METHODS: The study cohort comprised 34,120 adult men and women initially free of AF with information on GERD symptoms. Participants were followed from the baseline clinical examination (1 October 2006 to 30 June 2008) to March 31, 2018. RESULTS: During a median follow-up of 8.9 years, 1,221 cases of AF were diagnosed. When looking at the whole population, participants with much GERD symptoms did not have an increased risk of AF (HR: 1.01; CI: 95%, 0.82 to 1.24) while participants with little GERD symptoms had a 14% lower risk of AF compared those with no GERD symptoms (HR: 0.86; CI: 95%, 0.76 to 0.97). Among younger participants (<40 years of age), the risk of AF had a trend towards increased risk with increasing symptom load of GERD (little GERD symptoms, HR: 3.09; CI: 95%, 0.74 to 12.94 and much GERD symptoms, HR: 5.40; 95% CI: 0.82 to 35.58). Among older participants (≥65 years of age), we saw a slightly reduced risk of AF in participants with little symptoms (HR: 0.84; CI: 0.72 to 0.97) and no association among those with much GERD symptoms (HR: 1.06; 95% CI: 0.82 to 1.36). CONCLUSION: We did not find support for a clinically important association between symptoms of GERD and AF across all age groups but for some younger people, GERD might play a role in the development of AF. However, our estimates for this age group were very imprecise and larger studies including younger individuals are warranted.

Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation.

BACKGROUND: Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation. RESULTS: There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively. CONCLUSION: In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring.

Association of age at menarche, reproductive lifespan and age at menopause with the risk of atrial fibrillation: The HUNT study.

BACKGROUND: Age at menarche, reproductive lifespan, and age at menopause are associated with several cardiovascular diseases, but their relationship with atrial fibrillation (AF) is uncertain. METHODS: We linked information on all women who participated in the third survey of the population-based, longitudinal HUNT study in Norway with medical records from all local hospitals. A total of 14,632 women aged 60 or more were followed for validated incident AF. We retrieved age at menarche and age at menopause from the HUNT questionnaires. Reproductive lifespan was defined as the difference between age at menarche and age at menopause. We used Cox proportional hazards regression models to assess associations between AF and age at menarche, reproductive lifespan, and age at menopause. RESULTS: During a median follow-up of 8.17 years (136,494 person-years), 1217 (8.3 %) participants developed AF. In multivariable-adjusted analyses, we observed no associations between early or late age at menarche and AF (hazard ratios (HRs): <12 years: 0.85 [95 % confidence interval (CI), 0.65-1.12]; ≥16 years: 0.99 [95 % CI, 0.80-1.24] compared to those who attained menarche at 13-14 years). The HR for a reproductive lifespan shorter than 30 years was 0.91 [95 % CI, 0.72-1.15] compared to 34-37 years. Likewise, there was no clear association between premature or early age at menopause and AF (HRs: <40 years: 1.21 [95 % CI, 0.83-1.75]; 40-44 years: 0.97 [95 % CI, 0.77-1.22] compared to 50-54 years). CONCLUSIONS: In this population of women aged 60 years and over, the risk of AF was not associated with age at menarche, reproductive lifespan, or age at menopause.

Parity, infertility, age at first birth, and risk of atrial fibrillation: data from the HUNT study.

AIMS: Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited. METHODS AND RESULTS: We linked data from the population-based HUNT study and the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24 015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT study. A history of infertility was self-reported on the HUNT questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. During a median follow-up of 12.8 years, 1448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF [HR 1.21, 95% confidence interval (CI) 1.05-1.39]. A history of infertility was also associated with the risk of AF (HR 1.20, 95% CI 1.02-1.42). Among parous women, younger age at first birth (<20 vs. 20-29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI 1.03-1.40). CONCLUSION: Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old.

A higher number of births and a younger age at first birth are associated with a higher risk of cardiovascular disease. However, there is limited evidence on the associations between parity, age at first birth, and atrial fibrillation (AF). Moreover, the association between infertility and AF remains largely unexplored. We investigated the association between parity, infertility, age at first birth, and AF in a population-based cohort from Norway (the HUNT study) among women over 45 years old. Our findings reveal that women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF.

Effects of training adaption in endurance athletes with atrial fibrillation: protocol for a multicentre randomised controlled trial.

Endurance athletes have a high prevalence of atrial fibrillation (AF), probably caused by exercise-induced cardiac remodelling. Athletes diagnosed with AF are often advised to reduce the intensity and amount of training but the efficacy of this intervention has not been investigated in endurance athletes with AF. Effects of detraining in endurance athletes with atrial fibrillation is a two-arm international multicentre randomised (1:1) controlled trial on the effects of a period of training adaption on AF burden in endurance athletes with paroxysmal AF. One-hundred-and-twenty endurance athletes diagnosed with paroxysmal AF are randomised to a 16-week period of intervention (training adaption) or a control group. We define training adaption as training with a heart rate (HR) not exceeding 75% of the individual maximum HR (HRmax), and total duration of weekly training not exceeding 80% of the self-reported average before the study. The control group is instructed to uphold training intensity including sessions with HR ≥85% of HRmax. AF burden is monitored with insertable cardiac monitors, and training intensity with HR chest-straps and connected sports watches. The primary endpoint, AF burden, will be calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. Secondary endpoints include number of AF episodes, adherence to training adaption, exercise capacity, AF symptoms and health-related quality of life, echocardiographic signs of cardiac remodelling and risk of cardiac arrhythmias related to upholding training intensity. Trial registration number: NCT04991337. Study protocol version: 4.7 (Date 9 March 2023).

Effect of continuous positive airway pressure therapy on recurrence of atrial fibrillation after pulmonary vein isolation in patients with obstructive sleep apnea: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Whether treatment with continuous positive airway pressure (CPAP) reduces AF recurrence after catheter ablation with pulmonary vein isolation (PVI) is unknown. OBJECTIVE: The purpose of this study was to assess the effect of CPAP treatment on the recurrence and burden of AF after PVI in patients with OSA. METHODS: We randomized patients with paroxysmal AF and an apnea-hypopnea index (AHI) ≥15 events/hour to treatment with CPAP or standard care. Heart rhythm was monitored by an implantable loop recorder. AF recurrence after PVI was defined as any episode of AF lasting >2 minutes after a 3-month blanking period. RESULTS: PVI was performed in 83 patients. Thirty-seven patients were randomized to CPAP treatment and 46 patients to standard care. The AHI was reduced from 26.7 ± 14 events/hour to 1.7 ± 1.3 events/hour at follow-up in the CPAP group (P = .001). A total of 57% of patients in both the CPAP group and the standard care group had at least 1 episode of AF 3-12 months after PVI (P for difference = 1). AF burden after ablation was reduced in both groups, with no between-group difference (P = .69). CONCLUSION: In patients with paroxysmal AF and OSA, treatment with CPAP did not further reduce the risk of AF recurrence after ablation. PVI considerably reduced the burden of AF in OSA patients, without any difference between groups.

Exercising immune cells: The immunomodulatory role of exercise on atrial fibrillation.

Exercise training is generally beneficial for cardiovascular health, improving stroke volume, cardiac output, and aerobic capacity. Despite these benefits, some evidence indicates that endurance training may increase the risk of atrial fibrillation (AF), particularly in highly trained individuals. Among multiple mechanisms, autonomic tone changes and atrial remodeling have been proposed as main contributors for exercise-induced AF. However, the contribution of local and systemic immunity is poorly understood in the development of atrial arrhythmogenic substrates. Here we aim to update the field of immunomodulation in the context of exercise and AF by compiling and reconciling the most recent evidence from preclinical and human studies and rationalize the applicability of "lone" AF terminology in athletes.

High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.

AIM: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening. METHODS AND RESULTS: Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up. CONCLUSION: Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.

Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study.

BACKGROUND: Individuals with the metabolic syndrome are 3 times more likely to die of heart disease than healthy counterparts. Exercise training reduces several of the symptoms of the syndrome, but the exercise intensity that yields the maximal beneficial adaptations is in dispute. We compared moderate and high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with the metabolic syndrome. METHODS AND RESULTS: Thirty-two metabolic syndrome patients (age, 52.3+/-3.7 years; maximal oxygen uptake [o(2)max], 34 mL x kg(-1) x min(-1)) were randomized to equal volumes of either moderate continuous moderate exercise (CME; 70% of highest measured heart rate [Hfmax]) or aerobic interval training (AIT; 90% of Hfmax) 3 times a week for 16 weeks or to a control group. o(2)max increased more after AIT than CME (35% versus 16%; P<0.01) and was associated with removal of more risk factors that constitute the metabolic syndrome (number of factors: AIT, 5.9 before versus 4.0 after; P<0.01; CME, 5.7 before versus 5.0 after; group difference, P<0.05). AIT was superior to CME in enhancing endothelial function (9% versus 5%; P<0.001), insulin signaling in fat and skeletal muscle, skeletal muscle biogenesis, and excitation-contraction coupling and in reducing blood glucose and lipogenesis in adipose tissue. The 2 exercise programs were equally effective at lowering mean arterial blood pressure and reducing body weight (-2.3 and -3.6 kg in AIT and CME, respectively) and fat. CONCLUSIONS: Exercise intensity was an important factor for improving aerobic capacity and reversing the risk factors of the metabolic syndrome. These findings may have important implications for exercise training in rehabilitation programs and future studies.

Pathological and physiological hypertrophies are regulated by distinct gene programs.

BACKGROUND: This study aims to investigate changes that occur during progression and establishment of physiological and pathological cardiac hypertrophy, by microarray technology and functional annotations. DESIGN AND METHODS: Myocardial infarction leading to heart failure was induced in rats, with animals killed 1, 3, 7, 14, 42, and 92 days after coronary artery ligation. A second group was subjected to daily treadmill exercise and killed 1, 4, 24, and 48 h after a single exercise bout, or after 28 or 56 days of exercise training. RESULTS: Physiological hypertrophy was associated with less transcriptional alternation than pathological hypertrophy, indicating that posttranscriptional and translational regulation may be more important. The main difference between the two types of hypertrophy was that myocardial infarction was associated with downregulation of genes related to fatty acid metabolism, whereas no such change occurred after exercise training. Thus, fatty acid metabolism may distinguish adverse maladaptive hypertrophy from beneficial adaptive hypertrophy. CONCLUSION: This study points to specific genes and gene classes related to biological processes that may be important in these well-characterized rat models of physiological and pathological cardiac hypertrophy.

Exercise in individuals with atrial fibrillation.

BACKGROUND: Despite the high prevalence of atrial fibrillation (AF), there is a lack of recommendations for physical activity and exercise in individuals with AF, including athletes with AF. METHODS: With the aim to review studies that have investigated effects and safety of exercise in individuals with AF, we conducted a literature search in Pubmed using the key words atrial fibrillation AND exercise OR physical activity OR exercise/adverse effects OR adverse outcome. RESULTS: Observational data from one registry suggest that regular exercise is associated with reduced mortality in AF patients. Three randomized controlled trials (RCTs) have demonstrated that 12-week exercise interventions might reduce the burden of AF and improve exercise capacity by 10-16% in patients with paroxysmal or persistent AF. Three small RCTs suggest that exercise might improve exercise capacity with 15-41% in patients with permanent AF. Exercise might improve quality of life in patients with AF. Data on safety of exercise are sparse. No studies have evaluated the effect of exercise in athletes with AF. CONCLUSIONS: Despite weak evidence, we suggest that individuals with AF should exercise regularly after evaluation of underlying conditions. Recommendations should be individualized. There is a lack of data to support exercise recommendations in athletes with AF.