Feasibility of time-restricted eating and impacts on cardiometabolic health in 24-h shift workers: The Healthy Heroes randomized control trial.

Over a quarter of the workforce in industrialized countries does shift work, which increases the risk for cardiometabolic disease. Yet shift workers are often excluded from lifestyle intervention studies to reduce this risk. In a randomized control trial with 137 firefighters who work 24-h shifts (23-59 years old, 9% female), 12 weeks of 10-h time-restricted eating (TRE) was feasible, with TRE participants decreasing their eating window (baseline, mean 14.13 h, 95% CI 13.78-14.47 h; intervention, 11.13 h, 95% CI 10.73-11.54 h, p = 3.29E-17) with no adverse effects, and improved quality of life assessed via SF-36 (ClinicalTrials.gov: NCT03533023). Compared to the standard of care (SOC) arm, TRE significantly decreased VLDL particle size. In participants with elevated cardiometabolic risks at baseline, there were significant reductions in TRE compared to SOC in glycated hemoglobin A1C and diastolic blood pressure. For individuals working a 24-h shift schedule, TRE is feasible and can improve cardiometabolic health, especially for individuals with increased risk. VIDEO ABSTRACT.

Protocol for a randomised controlled trial on the feasibility and effects of 10-hour time-restricted eating on cardiometabolic disease risk among career firefighters doing 24-hour shift work: the Healthy Heroes Study.

INTRODUCTION: Career firefighters experience chronic circadian rhythm disruption, increasing their risk of cardiometabolic disease. The recent discovery that eating patterns regulate circadian rhythmicity in metabolic organs has raised the hypothesis that maintaining a consistent daily cycle of eating and fasting can support circadian rhythms and reduce disease risks. Preclinical animal studies and preliminary clinical trials have shown promising effects of time-restricted eating (TRE) to reduce disease risk without compromising physical performance. However, there is a lack of research on TRE in shift workers including firefighters. This study aims to investigate the feasibility and efficacy of 10-hour TRE on health parameters that contribute to cardiometabolic disease risks among career firefighters who work on a 24-hour shift schedule. METHODS AND ANALYSES: The Healthy Heroes Study is a randomised controlled parallel open-label clinical trial with 150 firefighters over 1 year. Firefighters are randomised with a 1:1 ratio to either the control or intervention group. The control group receives Mediterranean diet nutritional counselling (standard of care, 'SOC'). The intervention group receives the same SOC and a self-selected 10-hour TRE window. After the 2-week baseline, participants enter a 3-month monitored intervention, followed by a 9-month self-guided period with follow-up assessments. The impact of TRE on blood glucose, body weight, body composition, biomarkers (neuroendocrine, inflammatory and metabolic), sleep and mood is evaluated. These assessments occur at baseline, at the end of intervention and at 6, 9 and 12-month follow-ups. Temporal calorie intake is monitored with the smartphone application myCircadianClock throughout the study. Continuous glucose monitors, wrist-worn actigraphy device and questionnaires are used to monitor glucose levels, activity, sleep and light exposure. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Boards of the University of California San Diego and the Salk Institute for Biological Studies. Results will be disseminated through peer-reviewed manuscripts, reports and presentations. TRIAL REGISTRATION NUMBER: NCT03533023; Pre result.

Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological treatments are limited. OBJECTIVES: This study investigated the effect of ivabradine (selective blocker of the Ifunny channel in the sinoatrial node) on heart rate, quality of life (QOL), and plasma norepinephrine (NE) levels in patients with hyperadrenergic POTS defined by plasma NE >600 pg/ml and abnormal tilt table test. METHODS: In total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month. RESULTS: The average age was 33.9 ± 11.7 years, 95.5% were women (n = 21), and 86.4% were White (n = 23). There was a significant reduction in heart rate between placebo and ivabradine (p < 0.001). Patients reported significant improvements in QOL with RAND 36-Item Health Survey 1.0 for physical functioning (p = 0.008) and social functioning (p = 0.021). There was a strong trend in reduction of NE levels upon standing with ivabradine (p = 0.056). Patients did not experience any significant side-effects, such as bradycardia or hypotension, with ivabradine. CONCLUSION: Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.

Bilateral Orbital Metastases Masquerading as Ocular Myasthenia Gravis: A Case Report and Review of the Literature.

Ocular myasthenia gravis and orbital metastases have overlapping symptoms but divergent diagnostic and treatment strategies. Here, we present a 58-year-old female, with a 20-year history of advanced metastatic breast cancer, who presented to the neurology clinic with fatigue, muscle weakness, bilateral ptosis, and diplopia that worsened throughout the day. While the initial presentation was consistent with ocular myasthenia gravis, a subsequent evaluation revealed bilateral metastatic lesions of breast origin within the orbits. This case highlights the variable nature of metastatic disease and underscores the importance of a comprehensive neoplastic workup in patients with new-onset symptomatology and a prior history of advanced cancer despite purported remission status.

Autoantibody-Negative Immune-Mediated Necrotizing Myopathy Responds to Early and Aggressive Treatment: A Case Report.

Immune-mediated necrotizing myopathy (IMNM) is a rare idiopathic disease that is further classified by the presence of serum antibodies. A modicum of patients lack serum autoantibodies. Significantly elevated creatine kinase (CK) is highly characteristic of IMNM. The pathophysiology of IMNM is partially understood, and effective treatment options are limited, particularly in patients without serum autoantibodies. In this case, we report a 76-year-old male presenting with a four-month history of proximal muscle weakness. Muscle biopsy and serology confirmed the diagnosis of autoantibody-negative IMNM. Early and aggressive treatment with high-dose steroids and a course of intravenous immunoglobulin significantly reduced the patient's symptoms and CK within three months. This case serves as an example of an effective treatment outcome in a patient with this rare idiopathic necrotizing myopathy.

Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure.

Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.

Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome.

In animal models, time-restricted feeding (TRF) can prevent and reverse aspects of metabolic diseases. Time-restricted eating (TRE) in human pilot studies reduces the risks of metabolic diseases in otherwise healthy individuals. However, patients with diagnosed metabolic syndrome often undergo pharmacotherapy, and it has never been tested whether TRE can act synergistically with pharmacotherapy in animal models or humans. In a single-arm, paired-sample trial, 19 participants with metabolic syndrome and a baseline mean daily eating window of ≥14 h, the majority of whom were on a statin and/or antihypertensive therapy, underwent 10 h of TRE (all dietary intake within a consistent self-selected 10 h window) for 12 weeks. We found this TRE intervention improves cardiometabolic health for patients with metabolic syndrome receiving standard medical care including high rates of statin and anti-hypertensive use. TRE is a potentially powerful lifestyle intervention that can be added to standard medical practice to treat metabolic syndrome. VIDEO ABSTRACT.

Heart Failure and Diabetes Mellitus: Defining the Problem and Exploring the Interrelationship.

Type 2 diabetes mellitus and congestive heart failure are highly prevalent diseases with significant morbidity and mortality. These 2 diseases often occur concurrently because of shared risk factors such as coronary artery disease, and also because type 2 diabetes mellitus has direct cardiotoxic effects. Type 2 diabetes mellitus likely has a causative role in the development and prognosis of patients with heart failure. Optimal prevention and treatment of type 2 diabetes mellitus and heart failure likely involves identifying and treating their shared pathophysiologic features. Novel drug therapies, such as sodium-glucose co-transporter 2 inhibitors, offer an exciting potential to better understand the relationship between type 2 diabetes mellitus and heart failure, and may prove to have beneficial effects on cardiovascular outcomes in patients affected by these diseases.

Postural Orthostatic Tachycardia Syndrome: Prevalence, Pathophysiology, and Management.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating disease that predominantly affects young women. It is a multifactorial disorder that is characterized by severe tachycardia and orthostatic intolerance. Patients with POTS experience a variety of cardiac, neurological, and immunological symptoms that significantly reduce quality of life. In this review, a comprehensive framework is provided to aid in helping identify and treat patients with POTS. Given its heterogenous nature, it is crucial to understand each component of POTS in relation to one another instead of distinct parts. The framework highlights the overlap among the five main subtypes of POTS based on its pathophysiology (neuropathic, hypovolemic, primary hyperadrenergic, joint-hypermobility-related, and immune-related). Emphasis is placed on incorporating a multidisciplinary approach when treating patients with POTS, especially with a new focus towards immunotherapy. Although research has advanced our knowledge of POTS, there is still a critically unmet need to further our understanding and provide patients with the relief they need.