Pathophysiology of exercise intolerance in chronic diseases: the role of diminished cardiac performance in mitochondrial and heart failure patients

Objective: Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders. Methods: In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance. Results: Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01). Conclusions: Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life

Report from the Annual Conference of the British Society of Echocardiography, November 2017, Edinburgh International Conference Centre, Edinburgh

No abstract available

Bystander Phage Therapy: Inducing Host-Associated Bacteria to Produce Antimicrobial Toxins against the Pathogen Using Phages

Brevibacillus laterosporus is often present in beehives, including presence in hives infected with the causative agent of American Foulbrood (AFB), Paenibacillus larvae. In this work, 12 B. laterosporus bacteriophages induced bactericidal products in their host. Results demonstrate that P. larvae is susceptible to antimicrobials induced from field isolates of the bystander, B. laterosporus. Bystander antimicrobial activity was specific against the pathogen and not other bacterial species, indicating that the production was likely due to natural competition between the two bacteria. Three B. laterosporus phages were combined in a cocktail to treat AFB. Healthy hives treated with B. laterosporus phages experienced no difference in brood generation compared to control hives over 8 weeks. Phage presence in bee larvae after treatment rose to 60.8 ± 3.6% and dropped to 0 ± 0.8% after 72 h. In infected hives the recovery rate was 75% when treated, however AFB spores were not susceptible to the antimicrobials as evidenced by recurrence of AFB. We posit that the effectiveness of this treatment is due to the production of the bactericidal products of B. laterosporus when infected with phages resulting in bystander-killing of P. larvae. Bystander phage therapy may provide a new avenue for antibacterial production and treatment of disease

WearAble Project Protocol

This protocol describes in detail how we will conduct the project.</p

Application of non‐invasive bioreactance to assess hemodynamic function in patients with hypertrophic cardiomyopathy

Abstract Non‐invasive technologies have become popular for the clinical evaluation of cardiac function. The present study evaluated hemodynamic response to cardiopulmonary exercise stress testing using bioreactance technology in patients with hypertrophic cardiomyopathy. The study included 29 patients with HCM (age 55 ± 15 years; 28% female) and 12 age (55 ± 14 years), and gender matched (25% female) healthy controls. All participants underwent maximal graded cardiopulmonary exercise stress testing with simultaneous non‐invasive hemodynamic bioreactance and gas exchange. At rest, patients with HCM demonstrated significantly lower cardiac output (4.1 ± 1.3 vs. 6.1 ± 1.2 L/min; p < 0.001), stroke volume (61.5 ± 20.8 vs. 89.5 ± 19.8 mL/beat; p < 0.001), and cardiac power output (0.97 ± 0.3 vs. 1.4 ± 0.3watt; p < 0.001), compared to controls. At peak exercise, the following hemodynamic and metabolic variables were lower in HCM patients that is, heart rate (118 ± 29 vs. 156 ± 20 beats/min; p < 0.001), cardiac output (15.5 ± 5.8 vs. 20.5 ± 4.7 L/min; p = 0.017), cardiac power output (4.3 ± 1.6 vs. 5.9 ± 1.8 watts; p = 0.017), mean arterial blood pressure (126 ± 11 vs. 134 ± 10 mmHg; p = 0.039), and oxygen consumption (18.3 ± 6.0 vs. 30.5 ± 8.3 mL/kg/min; p < 0.001), respectively. Peak arteriovenous oxygen difference and stroke volume were not significantly different between HCM patients and healthy controls (11.2 ± 6.4 vs. 11.9 ± 3.1 mL/100 mL, p = 0.37 and 131 ± 50.6 vs. 132 ± 41.9 mL/beat, p = 0.76). There was a moderate positive relationship between peak oxygen consumption and peak heart rate (r = 0.67, p < 0.001), and arteriovenous oxygen difference (r = 0.59, p = 0.001). Functional capacity is significantly reduced in patients with HCM primarily due to diminished central (cardiac) rather than peripheral factors. Application of non‐invasive hemodynamic assessment may improve understanding of the pathophysiology and explain mechanisms of exercise intolerance in hypertrophic cardiomyopathy

Noninvasive Assessment of Cardiac Output in Advanced Heart Failure and Heart Transplant Candidates Using the Bioreactance Method

Objectives: The aim of the present study was to assess the validity and trending ability of the bioreactance method in estimating cardiac output at rest and in response to stress in advanced heart failure patients and heart transplant candidates. Design: This was a prospective single-center study. Setting: This study was conducted at the heart transplant center at the Freeman Hospital, Newcastle upon Tyne, UK. Participants: Eighteen patients with advanced chronic heart failure due to reduced left ventricular ejection fraction (19 ± 7%), and peak oxygen consumption 12.3 ± 3.9 mL/kg/min. Interventions: Participants underwent right heart catheterization using the Swan-Ganz catheter. Measurements and Main Results: Cardiac output was measured simultaneously using thermodilution and bioreactance at rest and during active straight leg raise test to volitional exertion. There was no significant difference in cardiac index values obtained by the thermodilution and bioreactance methods (2.26 ± 0.59 v 2.38 ± 0.50 L/min, p > 0.05) at rest and peak straight leg raise test (2.92 ± 0.77 v 3.01 ± 0.66 L/min, p > 0.05). In response to active leg raise test, thermodilution cardiac output increased by 22% and bioreactance by 21%. There was also a strong relationship between cardiac outputs from both methods at rest (r = 0.88, p < 0.01) and peak straight leg raise test (r = 0.92, p < 0.01). Cartesian plot analysis showed good trending ability of bioreactance compared with thermodilution (concordance rate = 93%) Conclusions: `Cardiac output measured by the bioreactance method is comparable to that from the thermodilution method. Bioreactance method may be used in clinical practice to assess hemodynamics and improve management of advanced heart failure patients undergoing heart transplant assessment

Pathophysiology of exercise intolerance in chronic diseases: the role of diminished cardiac performance in mitochondrial and heart failure patients

Objective: Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders. Methods: In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance. Results: Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p&lt;0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p&lt;0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p&lt;0.05), but increased by 21% in heart failure (p&lt;0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p&lt;0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p&lt;0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p&lt;0.01). Conclusions: Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life