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Altered cardiac reserve is a determinant of exercise intolerance in sickle cell anaemia patients.
Hammoudi, N, Ceccaldi, A, Haymann, JP, Guedeney, P, Nicolas-Jilwan, F, Zeitouni, M, Montalescot, G, Lionnet, F, Isnard, R, Hatem, SN
European journal of clinical investigation. 2022;(1):e13664
Abstract
BACKGROUND The underlying mechanisms of exercise intolerance in sickle cell anaemia (SCA) patients are complex and not yet completely understood. While latent heart failure at rest could be unmasked upon exercise, most previous studies assessed cardiac function at rest. We aimed to investigate exercise cardiovascular reserve as a potential contributor to exercise intolerance in adult SCA patients. METHODS In this observational prospective study, we compared prospectively 60 SCA patients (median age 31 years, 60% women) to 20 matched controls. All subjects underwent symptom-limited combined exercise echocardiography and oxygen uptake (VO2 ) measurements. Differences between arterial and venous oxygen content (C(a-v)O2 ) were calculated. Cardiac reserve was defined as the absolute change in cardiac index (Ci) from baseline to peak exercise. RESULTS Compared to controls, SCA patients demonstrated severe exercise intolerance (median peakVO2 , 34.3 vs. 19.7 ml/min/kg, respectively, p < .0001). SCA patients displayed heterogeneously increased Ci from rest to peak exercise (median +5.8, range 2.6 to 10.6 L/min/m²) which correlated with peakVO2 (r = 0.71, p < .0001). In contrast, the C(a-v)O2 exercise reserve was homogenously reduced and did not correlate with peakVO2 (r = 0.18, p = .16). While haemoglobin level and C(a-v)O2 were similar in SCA subgroups, SCA patients in the lower VO2 tertile had chronotropic incompetence and left ventricular diastolic dysfunction (left atrial peak longitudinal strain was reduced, and both E/e' ratio and left atrial volume index were increased) and were characterized by a reduced cardiac reserve, +5.0[4.2-5.5] compared to +6.7[5.5-7.8] L/min/m² for the rest of the patient cohort, p < .0001. CONCLUSIONS Altered cardiac reserve due to chronotropic incompetence and left ventricular diastolic dysfunction seems to be an important determinant of exercise intolerance in adult SCA patients.
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An observational study on the effect of hypercholesterolemia developed after living donor liver transplantation on cardiac event and graft failure.
Park, J, Lee, SH, Han, S, Oh, AR, Lee, SK, Choi, GS, Park, MS, Carriere, K, Ahn, J, Kim, GS
Scientific reports. 2021;(1):959
Abstract
This study sought to evaluate the association between newly-developed significant hypercholesterolemia within one year following living donor liver transplantation (LDLT) and long term outcomes in light of cardiovascular events and graft failure. From October 2003 to July 2017, 877 LDLT recipients were stratified according to development of significant hypercholesterolemia within one year following LDLT. The primary outcome was occurrence of a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and coronary revascularization after LDLT. The incidence of graft failure, defined as all-cause death or retransplantation, was also compared. A total of 113 (12.9%) recipients developed significant hypercholesterolemia within one year. The differences in incidences of cardiac related events and graft related events began emerging significantly higher in the hypercholesterolemia group after 24 months and 60 months since the LDLT, respectively. After adjustment using the inverse probability of weighting, the hazard ratio (HR) for MACE was 2.77 (95% confidence interval (CI) 1.16-6.61; p = 0.02), while that for graft failure was 3.76 (95% CI 1.97-7.17, p < 0.001). A significant hypercholesterolemia after LDLT may be associated with cardiac and graft-related outcome; therefore, a further study and close monitoring of cholesterol level after LDLT is needed.
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Empagliflozin Treatment Is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes.
Thirunavukarasu, S, Jex, N, Chowdhary, A, Hassan, IU, Straw, S, Craven, TP, Gorecka, M, Broadbent, D, Swoboda, P, Witte, KK, et al
Diabetes. 2021;(12):2810-2822
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Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and 31P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and 31P-MRS scans before and after 12 weeks' empagliflozin treatment. Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycemic control underwent an identical scan protocol at a single visit. Empagliflozin treatment was associated with significant improvements in phosphocreatine-to-ATP ratio (1.52 to 1.76, P = 0.009). This was accompanied by a 7% absolute increase in the mean left ventricular ejection fraction (P = 0.001), 3% absolute increase in the mean global longitudinal strain (P = 0.01), 8 mL/m2 absolute reduction in the mean myocardial cell volume (P = 0.04), and 61% relative reduction in the mean NT-proBNP (P = 0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected. Empagliflozin thus ameliorates the "cardiac energy-deficient" state, regresses adverse myocardial cellular remodeling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate HF in T2D.
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High Fasting Glycemia Predicts Impairment of Cardiac Autonomic Control in Adults With Type 2 Diabetes: A Case-Control Study.
Silva, LRB, Gentil, P, Seguro, CS, de Oliveira, GT, Silva, MS, Zamunér, AR, Beltrame, T, Rebelo, ACS
Frontiers in endocrinology. 2021;:760292
Abstract
INTRODUCTION Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes. OBJECTIVE To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements. MATERIALS AND METHODS This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR. RESULTS At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D. CONCLUSION Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.
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Associations of 24-Hour Urinary Sodium and Potassium Excretion with Cardiac Biomarkers: The Maastricht Study.
Martens, RJH, Henry, RMA, Bekers, O, Dagnelie, PC, van Dongen, MCJM, Eussen, SJPM, van Greevenbroek, M, Kroon, AA, Stehouwer, CDA, Wesselius, A, et al
The Journal of nutrition. 2020;(6):1413-1424
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BACKGROUND It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood. OBJECTIVES We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction. METHODS We included 2961 participants from the population-based Maastricht Study (mean ± SD age 59.8 ± 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors. RESULTS Median [IQR] 24-h UNaE and UKE were 3.7 [2.8-4.7] g/24 h and 3.0 [2.4-3.6] g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium. CONCLUSIONS Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports recommendations to increase potassium intake in the general population. In addition, it suggests that cardiac dysfunction and/or cardiomyocyte injury may underlie previously reported associations of lower potassium intake with CVD mortality.
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Culprit lesion morphology in young patients with ST-segment elevated myocardial infarction: A clinical, angiographic and optical coherence tomography study.
Fang, C, Dai, J, Zhang, S, Wang, Y, Wang, J, Li, L, Wang, Y, Yu, H, Wei, G, Zhang, X, et al
Atherosclerosis. 2019;:94-100
Abstract
BACKGROUND AND AIMS About 20% of patients with ST-segment elevated myocardial infarction (STEMI) are young adults. Morphological characteristics of culprit lesion in young STEMI patients have not been systematically evaluated in vivo. The present study aimed to investigate culprit lesion characteristics in young patients versus older patients using optical coherence tomography (OCT). METHODS 1442 STEMI patients who underwent OCT examination of culprit lesion were included and divided into young group (age ≤50 years, n = 400) and older group (age >50 years, n = 1042). Clinical characteristics, angiography and OCT findings were compared between the two groups. RESULTS Culprit lesions in STEMI patients aged ≤50 years had more plaque erosion (32.0% vs. 21.1%, p < 0.001) and larger minimal lumen area (2.3 ± 1.7 mm2vs. 1.9 ± 1.1 mm2, p < 0.001) than in those aged >50 years. As compared with older patients, lipid rich plaque (80.5% vs. 87.2%, p = 0.001), thin cap fibroatheroma (TCFA, 59.5% vs. 69.5%, p < 0.001), calcification (31.3% vs. 48.7%, p < 0.001), spotty calcification (25.3% vs. 36.1%, p < 0.001) and cholesterol crystals (26.3% vs. 38.4%, p < 0.001) were less frequently observed in young patients. A gradient increase in typical plaque vulnerability was observed from age ≤50 years to 50-70 years to >70 years. In multivariate regression analysis, age ≤50 years was independently associated with less frequency of plaque rupture, TCFA, spotty calcification, cholesterol crystals and smaller lumen area stenosis. CONCLUSIONS Morphological characteristics of culprit lesion in young STEMI patients were different from those in older patients. Patients aged ≤50 years had more plaque erosion and less vulnerable plaque features.
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Leptin trajectories from birth to mid-childhood and cardio-metabolic health in early adolescence.
Li, LJ, Rifas-Shiman, SL, Aris, IM, Mantzoros, C, Hivert, MF, Oken, E
Metabolism: clinical and experimental. 2019;:30-38
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OBJECTIVES Leptin is a hormone produced by adipose tissue that promotes satiety, and some evidence suggests that greater early life leptin exposure prevents excessive adiposity gain in later life. However, few studies have analyzed dynamic changes in leptin throughout childhood in relation to later cardio-metabolic health. Our study aims to identify distinct leptin trajectories in childhood, and to examine their associations with cardio-metabolic outcomes in adolescence. METHODS Among children in the Project Viva cohort born 1999-2002 in Massachusetts, we used latent class growth models to identify leptin trajectories independent of maternal BMI, child sex, race/ethnicity, size at birth and current age and size among 1360 children with leptin measured at least once at birth, early childhood (mean 3.3 ± SD 0.3 years), or mid-childhood (7.9 ± 0.8 years). At research visits in early adolescence (13.2 ± 0.9 years), we assessed cardio-metabolic outcomes including adiposity measures, fasting biomarkers, and blood pressure among 855 children. We then applied multiple regression models to examine associations of the leptin trajectories with these cardio-metabolic outcomes in early adolescence, adjusting for child age at outcome, maternal age, education, prenatal smoking and glucose, total gestational weight gain and paternal BMI. RESULTS The latent class growth model identified 3 distinct leptin trajectories: "low stable" (n = 1031, 75.8%), "high-decreasing" (n = 219, 16.1%) and "intermediate-increasing" (n = 110, 8.1%). In adjusted models, the intermediate-increasing leptin trajectory was associated with higher early adolescence adiposity measures (e.g. BMI z-score: 0.62 units; 95% confidence interval: 0.28, 0.96 and odds of obesity: 2.84: 1.17, 6.94), but lower systolic blood pressure (-0.46 z-score units; -0.74, -0.18), compared to the low-stable group. CONCLUSIONS Our findings on leptin trajectories in childhood suggest important differences and associations with later metabolic outcomes.
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Heart rate variability reduction is related to a high amount of visceral adiposity in healthy young women.
Triggiani, AI, Valenzano, A, Trimigno, V, Di Palma, A, Moscatelli, F, Cibelli, G, Messina, G
PloS one. 2019;(9):e0223058
Abstract
Several heart rate variability (HRV) studies show abnormalities in autonomic nervous control in obese and overweight subjects. However, some of the results appear to be controversial. Here we investigate the HRV profile in seventy adult normotensive women and its association with general and visceral adiposity. Specifically, we recorded the electrocardiographic (ECG) activity in subjects during a supine resting state for five minutes in a quiet room late in the morning. Total fat mass (TFM) and visceral adipose tissue (VAT) were instead estimated using dual-energy X-ray absorptiometry (DXA). Finally, we used simple a linear regression analysis of frequency and time-domain parameters to study the relationship between HRV and adiposity. Our data showed an overall reduction of the HRV related to an increase of TFM although this regression appeared significant only for high frequencies (HF). When the linear regression was applied between HRV variables and VAT, the slope of the line increases, thus unveiling a statistically significant relation (i.e. the more VAT, the lower HRV). Finally, a control analysis showed that age does not alter the relation between HRV and VAT when used as a confounding factor in multiple regression. To conclude, these findings point to abnormal activity of the autonomic nervous system (ANS) in subjects with an excess of VAT and represent a starting point to determine a non-invasive index of cardiac wellness for clinical and nutritional application.
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Exploring the complexity: the interplay between the angiotensin-converting enzyme insertion/deletion polymorphism and the sympathetic response to hemodialysis.
Ribas Ribeiro, L, Flores de Oliveira, J, Bueno Orcy, R, Castilho Barros, C, Damé Hense, J, Santos, F, Irigoyen, MC, Gonzalez, MC, Oses, JP, Böhlke, M
American journal of physiology. Heart and circulatory physiology. 2018;(4):H1002-H1011
Abstract
Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but the specific role of the insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele increases gene expression, it is a candidate polymorphism to interact with the ANS. The aim of the present study was to compare the behavior of heart rate variability (HRV) during HD, as a surrogate for ANS response to stressors, between the ACE genotypes. In a sample of patients with chronic kidney disease I/D ACE genotypes were assessed with PCR and HRV was measured before, in the second hour, and after a HD session. HRV parameters in the time and frequency domains were analyzed by repeated-measures mixed models according to the time of measurement and ACE polymorphism. HRV parameters in the frequency domain presented significantly different variations during the HD session between patients with or without the D allele. Only patients with the II genotype presented an increase in low-frequency normalized units and in the low frequency-to-high frequency ratio throughout HD. Patients with the II genotype seemed to have a more physiological response to the volemic and electrolytic changes that occur during HD, with greater sympathetic activation than patients with ID and DD genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of cardiovascular system regulation, we have found that the autonomic nervous system response to the acute volume removal during hemodialysis may be different between angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge, this is the first time that this specific interaction was analyzed during a volume removal intervention.
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UBC-Nepal Expedition: An experimental overview of the 2016 University of British Columbia Scientific Expedition to Nepal Himalaya.
Willie, CK, Stembridge, M, Hoiland, RL, Tymko, MM, Tremblay, JC, Patrician, A, Steinback, C, Moore, J, Anholm, J, Subedi, P, et al
PloS one. 2018;(10):e0204660
Abstract
The University of British Columbia Nepal Expedition took place over several months in the fall of 2016 and was comprised of an international team of 37 researchers. This paper describes the objectives, study characteristics, organization and management of this expedition, and presents novel blood gas data during acclimatization in both lowlanders and Sherpa. An overview and framework for the forthcoming publications is provided. The expedition conducted 17 major studies with two principal goals-to identify physiological differences in: 1) acclimatization; and 2) responses to sustained high-altitude exposure between lowland natives and people of Tibetan descent. We performed observational cohort studies of human responses to progressive hypobaric hypoxia (during ascent), and to sustained exposure to 5050 m over 3 weeks comparing lowlander adults (n = 30) with Sherpa adults (n = 24). Sherpa were tested both with (n = 12) and without (n = 12) descent to Kathmandu. Data collected from lowlander children (n = 30) in Canada were compared with those collected from Sherpa children (n = 57; 3400-3900m). Studies were conducted in Canada (344m) and the following locations in Nepal: Kathmandu (1400m), Namche Bazaar (3440m), Kunde Hospital (3480m), Pheriche (4371m) and the Ev-K2-CNR Research Pyramid Laboratory (5050m). The core studies focused on the mechanisms of cerebral blood flow regulation, the role of iron in cardiopulmonary regulation, pulmonary pressures, intra-ocular pressures, cardiac function, neuromuscular fatigue and function, blood volume regulation, autonomic control, and micro and macro vascular function. A total of 335 study sessions were conducted over three weeks at 5050m. In addition to an overview of this expedition and arterial blood gas data from Sherpa, suggestions for scientists aiming to perform field-based altitude research are also presented. Together, these findings will contribute to our understanding of human acclimatization and adaptation to the stress of residence at high-altitude.