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Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.
Gamble, DT, Ross, J, Khan, H, Unger, A, Cheyne, L, Rudd, A, Saunders, F, Srivanasan, J, Kamya, S, Horgan, G, et al
Circulation. Cardiovascular imaging. 2023;(10):e015782
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Abstract
BACKGROUND Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. METHODS In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. RESULTS Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m2, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). CONCLUSIONS Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. REGISTRATION URL: https://www. CLINICALTRIALS gov; Unique identifier: NCT04467411.
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Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia.
Koblinsky, ND, Anderson, ND, Ajwani, F, Parrott, MD, Dawson, D, Marzolini, S, Oh, P, MacIntosh, B, Middleton, L, Ferland, G, et al
Pilot and feasibility studies. 2022;(1):37
Abstract
BACKGROUND Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia. METHODS Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3-4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. RESULTS Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively). CONCLUSIONS High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03056508 .
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Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 1: overview and the central role for catecholamines and sympathetic nervous system.
Omerovic, E, Citro, R, Bossone, E, Redfors, B, Backs, J, Bruns, B, Ciccarelli, M, Couch, LS, Dawson, D, Grassi, G, et al
European journal of heart failure. 2022;(2):257-273
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Abstract
This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including β-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model.
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Detection of periodontal microorganisms in coronary atheromatous plaque specimens of myocardial infarction patients: A systematic review and meta-analysis.
Joshi, C, Bapat, R, Anderson, W, Dawson, D, Hijazi, K, Cherukara, G
Trends in cardiovascular medicine. 2021;(1):69-82
Abstract
BACKGROUND Microbial translocation from inflamed periodontal pockets into coronary atheroma via systemic circulation is one of the proposed pathways that links periodontitis and myocardial infarction (MI). The purpose of this systematic review is to determine the reported prevalence of periodontal microorganisms in coronary atheroma and/or aspirated clot samples collected from MI patients with periodontal disease. METHODOLOGY The "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines were followed. Six databases were systematically searched using Medical Subject Headings/Index and Entree terms. After a thorough screening, fourteen publications spanning over ten years (2007-2017) were eligible for this systematic review and meta-analysis. RESULTS Out of 14 included studies, 12 reported presence of periodontal bacterial DNA in coronary atherosclerotic plaque specimens. Overall, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were the most frequently detected periodontal bacterial species. Meta-analysis revealed that the prevalence of P. gingivalis was significantly higher than A. actinomycetemcomitans in coronary atheromatous plaque samples. Apart from periodontal microbes, DNA from a variety of other microbes e.g. Pseudomonas fluorescens, Streptococcus species, Chlamydia pneumoniae were also recovered from the collected samples. CONCLUSION Consistent detection of periodontal bacterial DNA in coronary atheroma suggests their systemic dissemination from periodontal sites. It should further be investigated whether they are merely bystanders or induce any structural changes within coronary arterial walls.
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Serum antibody response against periodontal bacteria and coronary heart disease: Systematic review and meta-analysis.
Joshi, C, Bapat, R, Anderson, W, Dawson, D, Cherukara, G, Hijazi, K
Journal of clinical periodontology. 2021;(12):1570-1586
Abstract
AIM: The present systematic review and meta-analysis assessed the strength of a reported association between elevated serum anti-periodontal bacterial antibody responses and coronary heart disease (CHD). MATERIALS AND METHODS Twenty original studies were identified after systematically searching five databases. The majority (n = 11) compared serum anti-Porphyromonas gingivalis (Pg) and/or anti-Aggregatibacter actinomycetemcomitans (Aa) IgG antibody responses between CHD patients and control participants. The strength of the association between serum anti-Pg antibodies and CHD (n = 10) and serum anti-Aa antibodies and CHD (n = 6) was investigated using a meta-analysis approach separately. RESULTS Most studies (61%) reported that the serum IgG antibody responses were elevated in CHD patients than in controls. The meta-analyses showed a significant association between elevated serum IgG antibody responses (anti-Pg and anti-Aa) and CHD, with pooled odds ratios of 1.23 [95% confidence interval (CI): 1.09-1.38, p = .001] and 1.25 (95% CI: 1.04-1.47, p = .0004), respectively. CONCLUSIONS A modest increase of CHD events in individuals with higher serum anti-Pg and anti-Aa IgG antibody responses may support their use as potential biomarkers to detect and monitor at-risk populations. However, the observed inconsistencies with the design and interpretation of immunoassays warrant standardization of the immunoassays assessing antibody responses against periodontal bacteria.
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Prognostic value of cardiac biomarkers in COVID-19 infection.
Sheth, A, Modi, M, Dawson, D, Dominic, P
Scientific reports. 2021;(1):4930
Abstract
Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. PubMed, Embase and Web of Science were searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.57, 95% CI 0.43-0.70, p < 0.001). Additionally, BNP levels were also significantly higher in patients who died or were critically ill (WMD 0.45, 95% CI - 0.21-0.69, p < 0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26-35.1, p = 0.03). A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.79, 95% CI 0.25-1.33, p = 0.004). Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.
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Food Addiction and Tobacco Use Disorder: Common Liability and Shared Mechanisms.
Zawertailo, L, Attwells, S, deRuiter, WK, Le, TL, Dawson, D, Selby, P
Nutrients. 2020;(12)
Abstract
As food addiction is being more commonly recognized within the scientific community, parallels can be drawn between it and other addictive substance use disorders, including tobacco use disorder. Given that both unhealthy diets and smoking are leading risk factors for disability and death, a greater understanding of how food addiction and tobacco use disorder overlap with one another is necessary. This narrative review aimed to highlight literature that investigated prevalence, biology, psychology, and treatment options of food addiction and tobacco use disorder. Published studies up to August 2020 and written in English were included. Using a biopsychosocial lens, each disorder was assessed together and separately, as there is emerging evidence that the two disorders can develop concurrently or sequentially within individuals. Commonalities include but are not limited to the dopaminergic neurocircuitry, gut microbiota, childhood adversity, and attachment insecurity. In addition, the authors conducted a feasibility study with the purpose of examining the association between food addiction symptoms and tobacco use disorder among individuals seeking tobacco use disorder treatment. To inform future treatment approaches, more research is necessary to identify and understand the overlap between the two disorders.
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Takotsubo syndrome in Heart Failure and World Congress on Acute Heart Failure 2019: highlights from the experts.
Keramida, K, Backs, J, Bossone, E, Citro, R, Dawson, D, Omerovic, E, Parodi, G, Schneider, B, Ghadri, JR, Van Laake, LW, et al
ESC heart failure. 2020;(2):400-406
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Duration of dual antiplatelet therapy in acute coronary syndrome.
Wilson, SJ, Newby, DE, Dawson, D, Irving, J, Berry, C
Heart (British Cardiac Society). 2017;(8):573-580
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Despite a large volume of evidence supporting the use of dual antiplatelet therapy in patients with acute coronary syndrome, there remains major uncertainty regarding the optimal duration of therapy. Clinical trials have varied markedly in the duration of therapy, both across and within trials. Recent systematic reviews and meta-analyses suggest that shorter durations of dual antiplatelet therapy are superior because the avoidance of atherothrombotic events is counterbalanced by the greater risks of excess major bleeding with apparent increases in all-cause mortality with longer durations. These findings did not show significant heterogeneity according to whether patients had stable or unstable coronary heart disease. Moreover, the potential hazards and benefits may differ when applied to the general broad population of patients encountered in everyday clinical practice who have markedly higher bleeding and atherothrombotic event rates. Clinicians lack definitive information regarding the duration of therapy in patients with acute coronary syndrome and risk scores do not appear to be sufficiently robust to address these concerns. We believe that there is a pressing need to undertake a broad inclusive safety trial of shorter durations of therapy in real world populations of patients with acute coronary syndrome. The clinical evidence would further inform future research into strategies for personalised medicine.
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Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.
Author et al, , Bateman, RM, Sharpe, MD, Jagger, JE, Ellis, CG, Solé-Violán, J, López-Rodríguez, M, Herrera-Ramos, E, Ruíz-Hernández, J, Borderías, L, et al
Critical care (London, England). 2016;:347
Abstract
[This corrects the article DOI: 10.1186/s13054-016-1208-6.].