Normal Exercise Research Articles

P.10 Compound CACNA1S heterozygosity resulting in a novel phenotype of congenital myopathy and early onset periodic paralysis: report of two probands

Skeletal muscle contraction is mediated by excitation-contraction coupling (ECC), a process involving the rapid elevation of cytosolic calcium. L-type voltage gated calcium channels located on T-tubule membranes are the voltage sensors of ECC. The dihydropyridine receptor (DHPR) contains the pore forming basic functional elements of these calcium channels and is encoded by the <i>CACNA1S</i> gene. Recessive mutations in the <i>CACNA1S</i> gene have been recently reported with a severe congenital myopathy and facial involvement. We describe two sisters with compound heterozygous mutations involving the <i>CACNA1S</i> gene. Both had neonatal hypotonia, muscle weakness, and delayed motor milestones. Prior to one year of age, periodic paralysis was evident as episodic flaccidity and loss of postural control. Periodic paralysis episodes continued to occur most notably with cold exposure, lasting around 10 minutes each. Lab evaluation revealed normal CPK. Electrophysiological evaluation revealed normal motor and sensory nerve conduction studies, and normal long exercise testing. Limb cooling and cold provocation led to clinical weakness and a drop in motor amplitude. Magnetic resonance imaging of the older sister showed symmetrical tigroid pattern fat replacement and atrophy of bilateral gluteus maximus muscles. Targeted next generation sequencing revealed two variants in the <i>CACNA1S</i> gene: both c.3526-2A>G and c.2831G>A (p.Cys944Tyr) are not described in the gnomAD database. Both variants co-segregated into affected sisters and Sanger sequencing revealed that c.3526-2A>G was inherited from the unaffected mother and c.2831G>A from the unaffected father, thus revealing a recessive pattern of inheritance. The c.3526-2A>G is expected to disrupt the acceptor splice site of intron 27 by <i>in silico</i> analysis, whereas the c.2831G>A variant replaces a highly conserved cysteine residue with tyrosine at codon 944 in the DIII-S5 of the Cav1.1 protein. This novel phenotype of a milder congenital recessive myopathy and early onset periodic paralysis expands the phenotypic spectrum of <i>CACNA1S</i> gene mutations.

NO RELATIONSHIP BETWEEN PULMONARY FUNCTION AND EXERCISE CAPACITY IN PEOPLE WITH POSTACUTE SEQUELAE OF SARS-COV-2 INFECTION

NO RELATIONSHIP BETWEEN PULMONARY FUNCTION AND EXERCISE CAPACITY IN PEOPLE WITH POSTACUTE SEQUELAE OF SARS-COV-2 INFECTION

Changes in cardiopulmonary exercise capacity and limitations 3-12 months after COVID-19.

To describe cardiopulmonary function during exercise 12 months after hospital discharge for coronavirus disease 2019 (COVID-19), assess the change from 3 to 12 months, and compare the results with matched controls without COVID-19. In this prospective, longitudinal, multicentre cohort study, hospitalised COVID-19 patients were examined using a cardiopulmonary exercise test (CPET) 3 and 12 months after discharge. At 3 months, 180 performed a successful CPET, and 177 did so at 12 months (mean age 59.3 years, 85 females). The COVID-19 patients were compared with controls without COVID-19 matched for age, sex, body mass index and comorbidity. Main outcome was peak oxygen uptake (V'O2 peak). Exercise intolerance (V'O2 peak <80% predicted) was observed in 23% of patients at 12 months, related to circulatory (28%), ventilatory (17%) and other limitations including deconditioning and dysfunctional breathing (55%). Estimated mean difference between 3 and 12 months showed significant increases in V'O2 peak % pred (5.0 percentage points (pp), 95% CI 3.1-6.9 pp; p<0.001), V'O2 peak·kg-1 % pred (3.4 pp, 95% CI 1.6-5.1 pp; p<0.001) and oxygen pulse % pred (4.6 pp, 95% CI 2.5-6.8 pp; p<0.001). V'O2 peak was 2440 mL·min-1 in COVID-19 patients compared to 2972 mL·min-1 in matched controls. 1 year after hospital discharge for COVID-19, the majority (77%), had normal exercise capacity. Only every fourth had exercise intolerance and in these circulatory limiting factors were more common than ventilator factors. Deconditioning was common. V'O2 peak and oxygen pulse improved significantly from 3 months.

Exercise inhibits JNK pathway activation and lipotoxicity via macrophage migration inhibitory factor in nonalcoholic fatty liver disease.

The macrophage migration inhibitory factor (MIF) expressed in hepatocytes can limit steatosis during obesity. Lipotoxicity in nonalcoholic fatty liver disease is mediated in part by the activation of the stress kinase JNK, but whether MIF modulates JNK in lipotoxicity is unknown. In this study, we investigated the role of MIF in regulating JNK activation and high-fat fostered liver lipotoxicity during simultaneous exercise treatment. Fifteen mice were equally divided into three groups: normal diet, high-fat diet, and high-fat and exercise groups. High-fat feeding for extended periods elicited evident hyperlipemia, liver steatosis, and cell apoptosis in mice, with inhibited MIF and activated downstream MAPK kinase 4 phosphorylation and JNK. These effects were then reversed following prescribed swimming exercise, indicating that the advent of exercise could prevent liver lipotoxicity induced by lipid overload and might correlate to the action of modulating MIF and its downstream JNK pathway. Similar detrimental effects of lipotoxicity were observed in in vitro HepG2 cells palmitic acid treatment. Suppressed JNK reduced the hepatocyte lipotoxicity by regulating the BCL family, and the excess JNK activation could also be attenuated through MIF supplementation or exacerbated by MIF siRNA administration. The results found suggest that exercise reduces lipotoxicity and inhibits JNK activation by modulating endogenous hepatic MIF in NAFLD. These findings have clinical implications for the prevention and intervention of patients with immoderate diet evoked NAFLD.

Effects of aerobic exercise and dietary intervention on testicular oxidative stress in obese mice

Through aerobic exercise and diet intervention on obese mice, the effects of exercise and diet intervention on testicular oxidative stress and p38MAPK-NF-κB pathway were investigated in obese mice. Seventeen C57BL/6J mice were randomly divided into a normal diet group (ND), and 37 mice were divided into a high-fat diet group (HFD), the high-fat diet accounted for 40% of fat. After 12 weeks of feeding, 3 obesity-resistant mice were excluded from the HFD group, and the remaining 34 were successfully modeled. The mice in ND group were then divided into normal diet control group (NC, n=8) and normal diet and exercise group (NE, n=9). The mice in HFD group were divided into obese high-fat diet control group (OC, n=8), obese high-fat diet and exercise group (OE, n=9), obese normal diet group (ONC, n=8), and obese normal diet and exercise group (ONE, n=9). Each group continued to feed for 8 weeks, and the NE, OE and ONE groups performed treadmill exercise for 8 weeks at a speed of 20 m/min, 60 min/d, 6 d/week. Blood and testicular tissue samples were collected 36～40 h after the last exercise. Serum testosterone and testicular oxidative stress (MDA, T-SOD, T-AOC) levels were detected by ELISA, and testicular p38MAPK-NF-κB levels were detected by RT-PCR and Western blot. Compared with the NC group, the body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels in the OC group were increased significantly (P＜0.01), while the levels of testicular SOD, testis coefficient and blood testosterone were decreased significantly (P＜0.01); the body fat parameters of the mice in the NE group were decreased significantly (P＜0.05), and the serum level of testosterone was increased significantly (P＜0.01). Compared with the OC group, the body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels were decreased significantly in the OE group (P＜0.05 or 0.01), and the testicular SOD and blood testosterone levels were increased significantly (P＜0.01); Body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels were decreased significantly in ONC group (P＜0.01), while testicular SOD level and testis coefficient were increased significantly (P＜0.05); Body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels of mice in ONE group were decreased significantly (P＜0.01), while testicular SOD, testis coefficient and blood testosterone levels were increased significantly (P＜0.01). Obesity induces oxidative stress in the testis of mice, up-regulates the level of p38MAPK-NF-κB, and reduces the level of blood testosterone; exercise, diet and exercise*diet interventions can reduce testicular oxidative stress and down-regulate testicular p38MAPK-NF-κB levels by reducing body fat.

Cardiopulmonary And Cognitive Testing Pre And Post Covid-19 Diagnosis

History: 23-year-old, athletic male, non-smoker enrolled in a research study to assess the impact of maximal exercise on cognitive performance. He completed a baseline cardiopulmonary exercise test (CPX) with concurrent cognitive tasks on a cycle ergometer and tested positive for COVID-19 6 days later. We conducted a second test 138 days later to examine impact of COVID-19 on CPX outcomes and cognitive performance. Physical Exam: During his first assessment, he presented afebrile with no signs of acute illness and passed the symptom and isolation status screener upon entry to the testing facility. He demonstrated normal exercise capacity (VO2) on the CPX (40.48 mL/min/Kg, 11.6 METs) and appropriate ventilatory and cardiovascular responses to exercise, reporting terminal muscular fatigue at 275 Watts (RER = 1.01, MHR = 175 bpm). A cognitive test of simple reaction speed at peak exertion yielded a score of 279 ms averaging 96.2% accuracy. Differential Diagnosis: COVID-19 associated impairment in exercise capacity Tests and Results: The participant described his illness as mild and did not require treatment or hospitalization. He reported symptoms such as headache, anosmia, dysgeusia, polydipsia, and palpitations, which resolved prior to the second CPX, and a weight loss of 3.5 kg was observed. CPX results revealed test duration (-3.25 min), peak VO2 (-1.68 mL/min/kg or -204.57 mL/min) terminating the CPX due to dyspnea at 250 W (RER = 1.03, MHR = 171 bpm). Cognitive testing revealed an 8% decrease in accuracy (96.2% to 88.5%) while no differences were noted in reaction speed. SpO2 was mildly reduced (-1%) but was not clinically significant. Additionally, heart rate recovery at 1-minute was impaired (31 to 27 bpm). Following recovery, accuracy on the cognitive test remained reduced (96.4% compared to 100% pre-COVID). Final/Working Diagnosis: impairment in exercise capacity and accuracy Treatment and Outcomes: Minor impairments in exercise capacity and cognitive performance were observed during CPX and cognitive testing following recovery from mild COVID-19 illness in this trained athlete, however, he had recovered with endurance sufficient to return to occupational and recreational activities.

Cardiometabolic Disease Risk in Normal Weight Obesity and Exercise Interventions for Proactive Prevention

PURPOSE: Normal weight obesity (NWO) is characterized by a normal body mass index but a high body fat mass percentage and low skeletal muscle mass, thereby increasing the risk of cardiometabolic dysfunction and morbidity. However, the effects of exercise intervention in reducing the risk of cardiometabolic disease in NWO have not been fully elucidated. Therefore, this review aimed to summarize the potential cardiometabolic disease risk and to provide implications of exercise interventions for the proactive prevention of cardiometabolic disease risk in NWO.METHODS: We searched and summarized the literature on the cardiometabolic risk factors in NWO. In addition, we summarized literature investigating the effects of exercise intervention on the cardiometabolic risk factors in NWO. We performed the literature search using PubMed, Web of Science, and Google Scholar databases.RESULTS: NWO was associated with increased visceral fat, ectopic fat, oxidative stress, inflammatory cytokines, insulin resistance, dyslipidemia, and subclinical atherosclerosis compared with normal weight lean. NWO requires exercise interventions that induce alterations in body composition, such as decreased body fat percentage and increased muscle mass. Resistance exercise (RE) and high-intensity interval exercise (HIIE) can improve lipid components and alter body composition in NWO. In addition, low-intensity blood flow restriction resistance exercise (BFR-RE) may enhance muscular strength and anaerobic power in NWO.CONCLUSIONS: The cardiometabolic disease risk is increased in NWO. We suggest that exercise interventions (RE, HIIE, and BFR-RE) may effectively prevent cardiometabolic disease risk and alter body composition in NWO. As this has potential implications for exercise interventions in NWO, further investigations are needed to find the optimal exercise for proactive prevention of cardiometabolic risk in NWO.

Limits to submaximal and maximal exercise in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) often have reduced exercise capacity, and it is unclear whether cardiovascular regulation during exercise is intact in these patients. We aimed to determine the relationship between cardiac output (Q̇c) and oxygen uptake (V̇o2), and stroke volume (SV) reserve in HCM compared with healthy participants and participants with left ventricular hypertrophy (LVH) but not HCM. Sixteen patients with HCM (48 ± 7 yr, 44% female), 16 participants with LVH (49 ± 5 yr, 44% female), and 61 healthy controls (CON: 52 ± 5 yr, 52% female) completed submaximal steady-state treadmill exercise followed by a maximal exercise test. V̇o2, Q̇c, SV, and arteriovenous oxygen difference were measured during rest and exercise, and Q̇c/V̇o2 slopes were constructed, The Q̇c/V̇o2 slope was blunted in HCM compared with CON and LVH [HCM 4.9 ± 0.7 vs. CON 5.5 ± 1.0 (P = 0.027) vs. LVH 6.0 ± 1.0 AU (P = 0.002)] and participants with HCM had a lower SV reserve (HCM 53 ± 33%, controls 83 ± 33%, LVH 82 ± 22%; HCM vs. controls P = 0.002; HCM vs. LVH P = 0.015). Despite a blunted Q̇c/V̇o2 slope, 75% of patients with HCM achieved ≥80% predicted V̇o2max by augmenting a-vo2 difference at maximal exercise (16.0 ± 0.8 mL/100 mL vs. 13.8 ± 2.7 mL/100 mL, P = 0.021). Patients with HCM do not appropriately match Q̇c to metabolic demand, primarily due to inadequate stroke volume augmentation. Despite this central limitation, many patients achieve normal exercise capacities by significantly increasing peripheral oxygen extraction.NEW & NOTEWORTHY Through state-of-the-art hemodynamic and oxygen uptake methodologies, this study found the cardiac output response to increasing metabolic demand is blunted among patients with hypertrophic cardiomyopathy (HCM), primarily due to a reduced stroke volume reserve. Many patients with HCM augment their peripheral oxygen extraction during maximal exercise to achieve normal exercise capacity and overcome ineffective matching of cardiac output. Peripheral adaptations that compensate for cardiac limitations may contribute to the heterogeneity of functional limitations observed within this patient population.

Real intensity of physical activity capacity of patients with chronic disease: a cross-sectional study

The aim of this study was to evaluate the real intensity level of exercise in a sample of patients with chronic disease from obesity, rheumatology, hematology and other departments involved in a hospital-based program of adapted physical activity (APA). For this cross-sectional study, we studied seventy-five patients with chronic disease and no beta-blocker treatment. They systematically performed a cardiopulmonary exercise test before participating in a supervised APA practice using a telemetry wireless system to monitor heart rate (HR) during the first session. Based upon the results of the functional evaluation of exercise performance, we studied two groups of patients: (1) No limitation in exercise performance (maximal oxygen uptake greater than or equal to 80% of the theoretical reference) and (2) limited exercise performance (maximal oxygen uptake less than 80% of the theoretical value). Fifty-two patients (69.3%) were women, mean age was 42.6 (± 13.8), and mean BMI was 36.7 (± 10.6). Most patients had been referred for obesity (57.3%). We found 39 patients with normal exercise capacities and 36 patients with limited exercise performance. There were no significant differences in demographic and clinical characteristics between the two groups. For all populations, the mean and median real intensity levels of exercise in a sample of patients were moderate (55–70% HR max) and were the same for both groups. During the most intensive 15-min bout of the APA session, the HR for patients in both groups was greater than 70% of the actual maximum HR. This study observed a moderate level of APA exercise intensity in patients suffering from various chronic diseases. We found no significant difference in intensity level of exercise between patients’ capacities, i.e., with and without limitation of their maximal performance.

Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea

Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise. To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF. This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics. Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls. Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, -0.134; 95% CI, -0.177 to -0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients. In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.

*Ketogenic Diets Exacerbating Hypercholesterolemia in APOE Variants and APOB Mutations-Potential Role for Measuring Intestinal Absorption of Lipids

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Familial Hypercholesterolemia (FH) is caused primarily by mutations in either LDL receptor, APOB, or PCSK9 genes. There are other genetic causes of LDL elevation including APOE4 variants. Objective/Purpose We present two patients with markedly elevated LDL suspicious for FH who were subsequently diagnosed with APOE3/4 variants while on ketogenic diets. We also present a patient with a known APOB mutation who had a marked elevation of LDL on a ketogenic diet. Methods Case 1: 58-year-old male with no prior medical history was found to have elevated cholesterol of 600mg/dL and LDL>455mg/dL while on a ketogenic diet. Prior to initiating the diet, his cholesterol was 206mg/dL and LDL was 132mg/dL. Genetic testing revealed a ApoE3/4 variant. His most recent cholesterol increased to 706mg/dL and LDL to >500mg/dL. Case 2: 53-year-old male with hypertension cholesterol of 282mg/dL and LDL of 212mg/dL went on a ketogenic diet and lost 100lbs. Follow up lipid panel demonstrated a cholesterol of 400mg/dL and LDL of 317mg/dL. Genetic testing revealed a APOE3/4 variant. Case 3: 45-year-old female with FH and known APOB missense mutation went on a ketogenic diet for weight loss. Prior to initiating the diet, her total cholesterol was 311 mg/dL and LDL was 211 mg/dL. While on the ketogenic diet, her total cholesterol was 550 mg/dL and LDL was 454 mg/dL. Her LDL decreased to 276mg/dl on a less strict ketogenic diet. Results All three patients had a normal exercise stress test, normal carotid duplex ultrasound, and coronary calcium score of zero. They refused the initiation of a statin. All 3 patients had the Boston Heart Cholesterol Balance Test performed that directly measures the absorption markers (beta-sitosterol, campesterol and cholestanol) for circulating plasma cholesterol. Only the patient with the APOB mutation had increased intestinal absorption of cholesterol, suggesting a response to ezetimibe. She agreed to initiate ezetimibe, her LDL subsequently decreased by 52% to 132mg/dl. Conclusions We hypothesize patients with APOE variants and APOB mutations could have an exaggerated elevation of their LDL levels while on ketogenic diets. Although these 3 patients did not demonstrate progressive atherosclerosis, the long-term effect of this diet is unknown. We recommend that all patients on a ketogenic diet have their LDL monitored and if there is a significant increase, undergo genetic testing for FH, APOE and other genetic variants. Since this patient group is often reluctant to start statins, the Cholesterol Balance Test may be useful to identify patients who may respond well to ezetimibe. Nothing to disclose.

Posterior cruciate ligament reconstruction with independent internal brace reinforcement: surgical technique and clinical outcomes with a minimum two year follow-up

PurposeWe developed an augmentation technique for PCL reconstruction with independent internal brace reinforcement and evaluated the functional outcome after PCL reconstruction employing autologous hamstrings augmented with an internal brace system for patients with isolated or combined grade 3 posterior instability who were treated with this technique.MethodsFrom January 2016 to January 2018, patients with isolated or combined grade 3 PCL tears who underwent single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces were studied. The function of the operated knee was evaluated according to the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity score. The patients were asked the level of returned to their previous sport. Posterior knee laxity was examined with a KT-1000 arthrometer, and data on range of motion (ROM), re-operation, and other complications were collected.ResultsA total of 33 consecutive patients who received single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces with a minimum two years follow-up were included in this study. Two patients had undergone this procedure during the study period and were not included in this study (one had combined bone fractures, and one patient had previous meniscus surgery). Thirty-one patients were available for final analysis. The mean follow-up was 45.35 ± 10.88 months (range 29–66 months). The average IKDC subjective knee evaluation scores from 51.65 ± 12.35 to 84.52 ± 6.42, the Lysholm score from 53.90 ± 11.86 to 85.68 ± 4.99, and the Tegner score from 2.81 ± 0.79 to 6.71 ± 1.83 (P < 0.05 for all). The mean total posterior side-to-side difference in knee laxity, assessed using a KT-1000 arthrometer, decreased from 12.13 ± 2.66 mm pre-operatively to 1.87 ± 0.56 mm post-operatively at 70° (P < 0.05). Most patients (29/31) had normal or near normal knee ROM post-operatively; two patients revealed a 6–15° loss of knee flexion compared with the contralateral knee. Twenty-nine patients (93.55%) returned to a normal daily exercise level. Twenty-three patients (74.19%) returned to competitive sports with high-level sports (Tegner score of 6 or above; eleven patients (35.48%) reported to be on the same level as well as the Tegner level); six patients (19.35%) returned to recreational sports (Tegner score of 4 or 5). Two patients had Tegner scores of 2 and 3, indicating poor function level. No patient needed PCL revision surgery during the follow-up period.ConclusionSingle-bundle PCL reconstruction with internal brace augmentation for PCL injury exhibited satisfactory posterior stability and clinical outcomes in patients with isolated or combined grade 3 PCL injuries at a minimum two year follow-up.

Is Exercise Blood Pressure Putting the Brake on Exercise Rehabilitation after Acute Type A Aortic Dissection Surgery?

(1) Background: Exercise is recommended to improve physical fitness in patients recovering from acute type A aortic dissection (ATAAD). However, surgery corrects the diseased blood vessels and reduces the risk of ATAAD, but it does not redefine a safe exercise blood pressure (BP) threshold. This review aimed to discuss whether the safe threshold of exercise BP can be upregulated after ATAAD surgery to increase exercise intensity with additional benefits. (2) Data sources: The PubMed databases were searched with the keywords “type A acute aortic dissection surgery”, “exercise”, “BP”, “stress”, and variations of these terms. (3) Study selection: Data from clinical trials, guidelines, and recent reviews were selected for review. (4) Results: Regular exercise can be considered a cardioprotective intervention for aortic dissection patients by attenuating hemodynamic responses at rest and during exercise. Previous studies have mainly focused on moderate-intensity aerobic exercise. In practice, the exercise systolic BP of some patients was higher than 160 mm Hg without adverse events, which indicates that the training intensity may be underestimated for patients after ATAAD surgery. Limited studies suggest a light-to-moderate resistance training for selected patients because it may cause a greater increase in BP. (5) Conclusions: Moderate-intensity continuous aerobic exercise supplemented by low-intensity resistance training is appropriate for cardiac rehabilitation after ATAAD surgery. The BP increase based on the normal exercise BP response, corresponding to the moderate-intensity is relatively safe. For high-risk post-ATAAD patients, considering the overall volume of training, personalizing the exercise regimen to remain within “safe” BP limits, and avoiding excessive fluctuations in BP should be the primary considerations for exercise training.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

P296 HIDDEN PERICARDIAL CONSTRICTION IN A PATIENT WITH CHRONIC PERICARDIAL EFFUSION AND “UNEXPLAINED” DYSPNEA

Abstract Constrictive physiology leads to exertional symptoms related to restrained diastolic filling and intracardiac/intrathoracic dissociation. However, these hemodynamic abnormalities might not be evident in some patients. A 55–year–old woman was referred to our center to perform a right and left cardiac catheterization because of “unexplained” dyspnea. Three years before she was found to have a large idiopathic pericardial effusion. Anti–inflammatory therapy did not result in any improvement. Since then, the patient complained dyspnea NYHA II–III, in the absence of any clinical and imaging sign of tamponade/pericardial constriction. At rest, there was no sign of constriction, but a relative hypovolemic status characterized by low pulmonary and filling pressures and cardiac output (CO) at the lower limits of normal. After a 500 mL saline load and passive legs raising, Kussmaul’s and “M” signs appeared on the right atrial pressure curve (Figure 1), the pulmonary artery wedge pressure (PAWP) – left ventricular end–diastolic pressure (LVEDP) gradient difference between expiration and inspiration was &amp;gt;5 mmHg (Figure 2), and ventricular systolic pressures went out of phase by 180°. Both right and left filling pressures as well as pulmonary pressures steeply increased in a concordant manner by about 10 mmHg after fluid load, in absence of a relevant increase in CO (Figure 3). Physical exercise performed thereafter showed an additional mild increase with a plateau pattern of all pressures, suggesting an upward–shift of the pressure/flow relationship (Figure 3). All these signs suggested a latent constrictive physiology. Despite this, the patient showed an optimal CO reserve coupled with a normal exercise capacity (peak oxygen consumption, VO2, 127% of predicted) that would have argued against our hypothesis. We then performed a diagnostic and evacuative pericardiocentesis. After the drainage of 130 ml of pericardial fluid, LV transmural pressure increased and CO at rest was fully normalized. Moreover, no hemodynamic sign of constriction could be observed even after a 1000 ml saline load. The patient reported disappearance of exertional breathlessness, objectivated by an increase in peakVO2 by 20% as compared with the previous test. Thus, our case underscores how subtle the hemodynamic impact of pericardial effusion can be, with the need of well–tailored diagnostic exams to explain otherwise “unexplained” patients’ symptoms, with potential therapeutic implications.

Effects of aerobic and resistance exercise on glycosylated hemoglobin (HbA1c) concentrations in non-diabetic Taiwanese individuals based on the waist-hip ratio.

BackgroundGlycosylated hemoglobin (HbA1c) reflects the average blood sugar over the past eight to twelve weeks. Several demographic and lifestyle factors are known to affect HbA1c levels. We evaluated the association of HbA1c with aerobic and resistance exercise in non-diabetic Taiwanese adults based on the waist-hip ratio (WHR).MethodsWe conducted this study based on TWB data collected from 90,958 individuals between 2008 and 2019. We estimated the Beta (β) coefficient and 95% confidence intervals (CI) for HbA1c using multivariate regression models.ResultsBased on the multivariate analysis, lower HbA1c levels were associated with both resistance exercise (β-coefficient = -0.027, 95% CI -0.037 to -0.017) and aerobic exercise (β-coefficient = 0.018, 95% CI, -0.023 to -0.013). Higher HbA1c levels were associated with abnormal WHR compared to normal WHR (β-coefficient = 0.091, 95% CI, 0.086 to 0.096). We detected an interaction between exercise and WHR (p for interaction = 0.0181). To determine the magnitude of the interaction, we performed additional analyses (with the reference group being ’abnormal WHR with no exercise’) and observed substantial decreases in HbA1c regardless of the WHR and exercise category. However, the largest reduction occurred in the ’normal WHR and resistance exercise’ group (β = -0.121, 95% CI, -0.132 to -0.109).ConclusionsWe found that normal resistance exercise, coupled with a normal WHR was significantly associated with lower HbA1c levels among non-diabetic individuals in Taiwan.

The Impact of Removal of Exercise for 3 Days on Glycemic Control in Older Active Adults

Postprandial glycemia (PPG) predicts cardiovascular disease, and 3 days of physical inactivity impairs PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if PPG was impaired in active older adults (old) following a 3 day removal of exercise compared to active young adults. In this randomized, crossover study, 10 older (73.0 ± 1.9 yrs) and 9 young (32.8 ± 1.8 yrs) habitually active (≥90 min/week of exercise) adults completed a 3 day period of exercise removal (NOEX) and a 3 day period of normal exercise maintenance (EX), separated by ≥ 1 week. Diet was standardized across phases. Glycemic control (GC) (2 hour PPG, peak glucose values, and standard deviation (STDEV) of blood glucose values) was assessed via continuous glucose monitoring (IPro2, Enlite Sensors, Medtronic Inc., Northridge, CA) during both phases. No differences in body mass index (Old: 26.5 ± 1.3, Young: 24.8 ± 1.0 kg/m2, p&gt;0.05) existed between groups. Both groups had a similar reduction in activity during NOEX (Old: ‐64.6% ± 6.2, Young: ‐55.7% ± 4.9, p&gt;0.05). There were significant main effects (p&lt;0.05) in PPG of age (Old: 116±1.2 mg/dL, Young: 106 ± 1.3 mg/dL), phase (Inactive: 113 ± 1.3 mg/dL, Active: 109 ± 1.2 mg/dL), and time (0 min: 99 ± 2.0, 30 min: 118 ± 2.0, 60 min: 117 ± 2.0, 90 min: 112 ± 2.0, 120 min: 108 ± 2.0 mg/dL), but no interaction (p&gt;0.05). Further, a trend (p=0.06) for significant main effect of age (Old: 149±5.6, Young: 133±5.9 mg/dL) and phase (p&lt;0.05; Inactive: 145±4.4, Active: 136±4.4 mg/dL) were found for peak glucose values. Significant main effects (p&lt;0.05) exist for age (Old: 15.3±1.2, Young: 11.3±1.2) and phase (Inactive: 14.4±0.97, Active: 12.2±0.97) for blood glucose STDEV. These results indicate that older adults have impaired GC compared to young adults and that removal of exercise impairs GC. Yet, the impairment in GC with exercise removal is not different between old and young adults when the decrease in daily physical activity is similar.

Physical Activity Capacity Assessment of Patients with Chronic Disease and the Six-Minute Walk Test: A Cross-Sectional Study.

Background: This study aimed to evaluate the efficacy of the Six-Minute Walk Test (6MWT) to determine the physical activity capacities of patients with chronic disease. Methods: For this cross-sectional study, we investigated 156 patients with chronic disease and no beta-blocker treatment. They systematically performed a maximal cardiopulmonary exercise test to determine their heart rate peak (HRPeak) and maximal oxygen uptake (V’O2max). We considered two groups of patients based upon the results of the functional evaluation of exercise performance: (1) No limitation in exercise performance (V’O2max greater or equal to 80% of the theoretical reference) and (2) limited exercise performance (V’O2max less than 80% of the theoretical value). All patients also received a 6MWT on the same day as the exercise test. Results: We found 68 (43.6%) patients with normal exercise capacities and 88 (56.4%) patients with limited exercise performance. In this sample, 6MWT mean distances were 510 (87) and 506 (86) m, respectively. There were no significant differences between the two groups for distance and end-test heart rate. The correlation between matrix V’O2max measured during the maximal incremental exercise test and the 6MWT distance displayed a positive slope (r = 0.549 CI95 [0.431–0.656]—p < 0.001). Conclusion: Our results showed a moderate relationship between 6MWT and physical activity capacity for patients with chronic disease.

Assessment of Cardiac Contribution to Exercise Intolerance in Pediatric Bilateral Lung Transplant Recipients

<h3>Purpose</h3> Exercise intolerance is common among lung transplant (LTx) recipients. However, there is limited data in pediatrics. Since the heart and lungs work in concert with each other, we aim to assess the cardiac contribution to exercise intolerance in pediatric LTx recipients by examining the prevalence of traditional cardiac risk factors (CRFs) and their performance on cardiopulmonary exercise testing (CPET). <h3>Methods</h3> All pediatric LTx recipients followed at a single center who had a resting echocardiogram (echo), were able to exercise, and had a routine CPET in the last 2 years were included. CRFs including hypertension, hyperlipidemia, diabetes mellitus (DM), body mass index (BMI), activity level, and smoking history were assessed. CPET-derived maximal oxygen consumption (VO2_max) and % predicted peak VO2 (ppVO2_max) were used to assess exercise tolerance. Left ventricular (LV) systolic and diastolic function were also assessed on resting echo. <h3>Results</h3> 11 bilateral LTx patients (7M, 4F, and median age 21 years, range 17-28 years) formed the cohort. Median time since LTx is 6 years, range 2-10 years. The majority of patients (8, 73%) had multiple CRFs: 7 (64%) had hypertension, 7 (64%) hyperlipidemia, 6 (55%) DM, 2 with BMI ≥25 kg/m², and 6 (55%) sedentary lifestyle. None had a smoking history. On resting echo, all had normal LV systolic function. 5 (45%) had LV diastolic dysfunction. On CPET, 9 (82%) had abnormal ppVO2_max ≤85%, even with maximal patient effort. None had ischemia. Surprisingly, only 2 of the 9 had a pulmonary limitation to exercise with abnormal breathing reserve (<25%) to account for abnormal ppVO2_max. 6 had a cardiac limitation to exercise attributed to inability to augment stroke volume (decreased % predicted peak O2 pulse). 1 had an abnormal respiratory exchange ratio (RER <1.10), with a normal % predicted peak O2 pulse and a chronotropic deficit (achieving 60% predicted peak heart rate). Of note, 2 patients had normal exercise tolerance with ppVO2_max >85%. <h3>Conclusion</h3> Despite maximal effort, low exercise tolerance is common among pediatric LTx recipients. The high prevalence of CRFs, diastolic dysfunction, and inability to augment stroke volume suggest a potential cardiac contribution to exercise intolerance for this cohort. Further studies are needed to define potential cardiac issues in exercise tolerance in pediatric LTx recipients.

Aerobic exercise promotes the expression of ATGL and attenuates inflammation to improve hepatic steatosis via lncRNA SRA

The role of aerobic exercise in preventing and improving non-alcoholic fatty liver has been widely established. SRA is a long non-coding RNA, which has received increasing attention due to its important role in lipid metabolism. However, it is unclear whether aerobic exercise can prevent and treat hepatic lipid accumulation via SRA. The mice were randomly divided into four groups as follows, normal control group, normal aerobic exercise group, high-fat diet group (HFD), and high-fat diet plus aerobic exercise (8 weeks, 6 days/week, 18 m/min for 50 min, 6% slope) group (HAE). After 8 weeks, the mice in the HAE group showed significant improvement in hepatic steatosis. Body weight as well as blood TC, LDL-C, and liver TG levels were significantly lower in the HAE group than in the HFD group. Compared with the HFD group, the expression of SRA was markedly suppressed and the expression of ATGL was significantly increased in the HAE group. Additionally, the JNK/P38 signaling was inhibited, the pro-inflammatory factors were down-regulated, and the anti-inflammatory factor was increased. In addition to this, the same results were shown in experiments with overexpression of SRA. The results of this study provided new support for aerobic exercise to improve hepatic lipid metabolism via lncRNA.