Exercise Tolerance Test Research Articles

Effects of 3\u2009months of detraining following cardiac rehabilitation in patients with atrial fibrillation

BackgroundAtrial fibrillation negatively impacts physical fitness and health-related quality of life. We recently showed that 3 months of physiotherapist-led exercise-based cardiac rehabilitation improves physical fitness and muscle function in elderly patients with permanent atrial fibrillation and concomitant diseases. Little is, however, known about the consequences for physical fitness, physical activity level, and health-related quality of life after ending the rehabilitation period.MethodsProspective 3 months follow-up study of 38 patients out of 40 eligible (10 women) who, as part of a randomized controlled trial, had completed a 3 months physiotherapist-led cardiac rehabilitation resulting in improved physical fitness,. In the current study, the participants were instructed to refrain from exercise for 3 months after completion of the rehabilitation period. Primary outcome measure was physical fitness measured as highest achieved workload using an exercise tolerance test. Secondary outcome measures were muscle function (muscle endurance tests), physical activity level (questionnaire and accelerometer), and health-related quality of life, (Short Form-36), as in the preceding intervention study. We used the Wilcoxon Signed Rank test to analyse differences between the end of rehabilitation and at follow-up. The effect size was determined using Cohen’s d .ResultsExercise capacity and exercise time significantly decresead between end of rehabilitation and at follow-up (p < .0001 for both). A significant reduction in shoulder flexion repetitions (p = .006) was observed as well as reduced health-related quality of life in the Short Form-36 dimensions Physical Function (p = .042), Mental Health (p = .030), and Mental Component Score (p = .035). There were, however, no changes regarding objective and subjective physical activity measurements.ConclusionIn older patients with permanent atrial fibrillation, previously achieved improvements from physiotherapist-led exercise-based cardiac rehabilitation in physical fitness and muscle function were lost, and health-related quality of life was impaired after ending the rehabilitation period. A strategy for conserving improvements after a rehabilitation period is essential.

Exercise Tolerance Test Examination for Determination of Obesity Paradox in Patients with Systolic Heart Failure. A Clinical Comparative Study

Aims and objectives: Current study was conducted in Department of cardiology, Hayatabad medical complex Peshawar, for one year of duration. The aims and objective of this study was to deliver health awareness and description of a biological hypothesis i.e. obesity paradox, among our community. Methodology: 250 patients with a history of cardiac complications were selected and divided into two different groups. 100 individuals with BMI &gt; 25 were in group A and their history of systolic heart failure was positive while in Group-B 150 patients with BMI&lt; 35 were selected and their systolic heart failure history were negative. Conclusion: Obesity paradox provides survival against systolic heart failure in high BMI cardiac patients this was the findings of this study. On the other side cardiorespiratory fitness also play an important role in severity, and survival. It has seen that obesity was found protective in cardiac diseases and there is a strong relationship between body mass index and obesity paradox in heart failure. The standard mean deviation levels of BMI, systolic blood pressure, percentage of ECG variation, oxygen saturation of exercise tolerance test were significant (P&lt;0.005) in group-B as compared to the group-A. Keywords: Obesity paradox, systolic heart failure, Body mass index, oxygen saturation

SILENT MYOCARDIAL ISCHEMIA AMONG ASYMPTOMATIC TYPE-2 DIABETIC PATIENTS

Objective: To determine the frequency of silent myocardial ischemia among asymptomatic type-2 diabetes mellitus patients. Methodology: This was a Cross sectional descriptive study conducted, after approval from the institutional ethical and research committee. A total of 90 asymptomatic type-2 diabetic patients were recruited for the present study. After informed written consent participants were subjected to a symptom-limited exercise tolerance test to detect the presence of silent myocardial ischemia. Descriptive statistics were applied to find frequencies and percentages for qualitative variables, and mean and standard deviation was used for quantitative variables. SPSS version22 was used for data analysis. Results: Among 90 type-2 asymptomatic diabetic patients, the frequency of silent myocardial ischemia was 36.7% (n=33). The frequency of silent myocardial ischemia among males and females was 57.6% and 42.4% respectively. Frequency of silent myocardial ischemia was found significantly more among patients with family history of CAD (60.6% vs 39.4%; p=0.029), prolonged duration of diabetes (15.2% vs 22.2% vs 63.6%; p=0.026) and group of patients with older age (9% vs 39.4 vs 51.6%; p=0.034). With respect to hypertension, smoking, obesity, and gender didn’t show statistically significant variation in the occurrence of silent myocardial ischemia. Conclusion: More than one third patients of asymptomatic type-2 diabetes mellitus had silent myocardial ischemia. Those with a family history of CAD, prolonged duration of diabetes, and participants with older age were more at risk of underlying silent myocardial ischemia.

Association of Central Obesity with Cardiovascular Diseases

Background: An increased trend of central obesity in general population has increased their risk of cardiovascular disease in various populations. Aims: To find an association between central obesity and cardiovascular disease. Study Design: Survey based study Place and Duration of Study: Department of Cardiology, MTI Lady Reading Hospital, Peshawar from 1st October 2020 to 30th September 2021. Methodology: Four hundred and twenty community participants were assessed for their central obesity via waist circumference measurement. Their lipid profiling, fasting blood sugar and exercise tolerance test was also conducted. Results: The mean age was 56.77±12.6 years with 61.9% females and 38.09% as male participants. The waist circumference ≥90cm in males was 7.5% while it was 15.3% in females. The socioeconomic status of the males and females with higher waist circumference was more as low to middle class. The odds ratio comparison within males and females showed a significant variance among ages, BMI and socioeconomic status in term of family income. The biochemical analysis of various participants blood samples showed dyslipidemia, ischemia and risk of atherosclerosis to be higher in central obesity participants than normal weight (p value &lt;0.005). Conclusion: There is a strong association of central obesity and cardiovascular diseases. Keywords: Association, Central Obesity, Cardiovascular disease

Echocardiographic assessment of diastolic function in non-ST elevation acute coronary syndrome patients and its association with in-hospital diagnosis

Objective: This study was conducted to evaluate the association of echocardiographic parameters used in left ventricular (LV) diastology with the early results of non-ST elevation acute coronary syndrome (NSTE-ACS) workup in the hospital. Methods: This cross-sectional study was performed on patients presenting with acute chest pain and a diagnosis of NSTE-ACS including only patients with unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI). All patients underwent transthoracic echocardiography in the emergency room (ER) within 12 hours of the last episode of chest pain. An invasive approach was not uniformly pursued in all of the patients so analysis was performed in two different settings. First, analysis was performed in the patients that underwent coronary angiography (CAG) and echocardiographic data were compared between those with normal and abnormal CAG results. Finally, echocardiographic data of the patients with normal diagnostic results (i.e., normal exercise tolerance test (ETT), myocardial perfusion imaging (MPI) or coronary angiography (CAG) results) were compared with the data of the patients with abnormal test results. Results: Eighty patients with a mean age of 54.43 ± 12.38 years were included in the study, of whom 57 (71.2%) were male. Fifty-three patients underwent CAG. In these 53 patients, there was significant difference in mitral annular velocity in early diastole (e’), ratio of mitral inflow velocity to e’ (E/e’), left ventricular end-diastolic diameter (LVEDD) and left ventricular end-diastolic pressure (LVEDP) between patients with coronary artery involvement and those with normal coronary artery (P&lt;0.05). The area under the receiver operating characteristic (ROC) curve to predict CAG results for e’, E/ e’, LVEDD and LVEDP was more than 0.65. The sensitivity and specificity of the LV diastolic dysfunction for predicting coronary involvement was 94.4% and 35.29%, respectively. Comparison of echocardiographic data between patients with normal test results (non-invasive and invasive) and those with abnormal diagnostic tests showed a significant difference in e’, E/e’, acceleration time of E, LV end-diastolic diameter index, size of interventricular septum and left atrial volume. Conclusion: The results suggest that diastolic dysfunction data can be used as an adjunctive method to evaluate ACS patients in the ER.

Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial

BackgroundDetection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined. ObjectivesThe authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters. MethodsThis was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters. ResultsAmong 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684). ConclusionsIn patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)

Demographic Characteristics and Risk Factors of Coronary Artery Disease in Patients Undergoing Percutaneous Coronary Intervention at a Tertiary Care Hospital in Islamabad

Objective: To determine the demographic characteristics and risk factors of coronary artery disease in patients undergoing percutaneous coronary intervention (PCI) at cardiology department of a tertiary care hospital in Islamabad. Materials and methods: This descriptive cases series study was done at cardiology department of Pakistan Institute of Medical Sciences (PIMS) Islamabad, during nine months of period from January to September 2021. All the patients having coronary artery disease based on clinical history and diagnosis including electrocardiogram (ECG), biochemical markers, or non-invasive tests like, echocardiography, exercise tolerance test (ETT), Thallium stress test and selected for PCI and of either gender were included. Pre PCI LVEF was assessed. All the patients underwent detailed medical history and routine laboratory investigation to assess the demographic information, risk factors of coronary artery diseases and indication of percutaneous coronary intervention (PCI). All the data was collected via self-made study proforma. Data was entered and analyzed by SPSS version 26. Results: A total of 724 patients with coronary artery disease and underwent (PCI) were studied, their average age was 55.72+10.04 years and average BMI was 25.70+3.14 kg/m2. Males were in majority 76.8%. Out of all 63.4% cases were hypertensive, 29.0% were diabetics, 41.4% having family history of CVD, 30.9% had a history of daily used of tobacco as shown in table.1 Pre PCI EF &lt;30% was in most of the cases 59.9% and elective PCI status was 86.2%. As per anginal classification the class II and III were most common 60.1% and 27.2% respectively. Most of the cases 87.2% having intermediate PCI risk sore. Conclusion: As per study conclusion hypertension, diabetes, smoking and family history were observed to the risk factors for CAD and intermediate PCI risk score was most frequent. Demographically age more than 45 years and males were commonest. Keyword: CAD, Risk score, PCI, age, gender

Evaluation of indices for predicting recovery of exercise tolerance in patients surviving allogenic hematopoietic stem cell transplantation.

Decline in physical function in the early stage after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major challenge. Exercise tolerance tests, such as the 6-min walk test, are useful markers for predicting exercise tolerance and various other traits, including cardiometabolic risk and non-relapse mortality. This retrospective cohort study aimed to investigate and identify predictors of recovery of exercise tolerance in the early stage after allo-HSCT. Ninety-eight patients were classified into recovery and non-recovery groups according to the median 6-min walk distance (6MWD) at discharge. Logistic regression analysis revealed that pre-post change in knee extensor strength (ΔKES) and hematopoietic cell transplantation comorbidity index were useful predictors of recovery of exercise tolerance at discharge and moderate predictors of 6MWD recovery in the early post-transplant period. Receiver operating characteristic analysis showed that pre-transplant ΔKES was an accurate predictor of 6MWD recovery in the early post-transplant period. The cutoff point for ΔKES calculated using the Youden index was - 1.17 Nm/kg. The results of this study emphasize the importance of the need for programs designed to prevent muscle weakness in the early period after allo-HSCT. The results from markers of recovery of exercise tolerance are promising and can be used for patient education in rehabilitation programs after allo-HSCT.

Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients.

Background: Pathogenic variants in phospholamban (PLN, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN p.Arg14del carriers. During collagen synthesis and breakdown, propeptides are released into the circulation, such as procollagen type I carboxy-terminal propeptide (PICP) and C-terminal telopeptide collagen type I (ICTP).Aim: To investigate if PICP/ICTP levels in blood are correlative biomarkers for clinical disease severity and outcome in PLN p.Arg14del variant carriers.Methods: Serum and EDTA blood samples were collected from 72 PLN p.Arg14del carriers (age 50.5 years, 63% female) diagnosed with ACM (n = 12), DCM (n = 14), and preclinical variant carriers (n = 46). PICP levels were measured with an enzyme-linked immune sorbent assay and ICTP with a radio immuno-assay. Increased PICP/ICTP ratios suggest a higher collagen deposition. Clinical data including electrocardiographic, and imaging results were adjudicated from medical records.Results: No correlation between PICP/ICTP ratios and late gadolinium enhancement (LGE) was found. Moderate correlations were found between the PICP/ICTP ratio and end-diastolic/systolic volume (both rs = 0.40, n = 23, p = 0.06). PICP/ICTP ratio was significantly higher in patients with T wave inversion (TWI), especially in leads V4–V6, II, III, and aVF (p < 0.022) and in patients with premature ventricular contractions (PVCs) during an exercise tolerance test (p = 0.007).Conclusion: High PICP/ICTP ratios correlated with clinical parameters, such as TWI and PVCs. Given the limited size and heterogeneity of the patient group, additional studies are required to substantiate the incremental prognostic value of these fibrosis biomarkers in PLN p.Arg14del patients.

Effect of low dose nebulized morphine on respiratory function improvement in mustard gas-exposed patients: A double-blind crossover clinical trial study.

Background:Mustard is one of the most destructive chemical gases used in chemical warfare. Several studies showed effectiveness of inhaled morphine as a secondary treatment for the improvement of dyspnea. Therefore, this study aimed at determining the efficacy of low dose inhaled morphine for respiratory function improvement in patients who were exposed to the mustard gas.Methods:This study was designed as a cross-over double-blinded clinical trial. Patients exposed to mustard gas were randomly assigned into two groups: 1) received 0.4 mg of morphine by inhalation and 2) received 5 ml of normal saline serum as a placebo in the same manner. After a washout period of one week, the first group received the placebo and the second group received morphine for 5 days. Spirometric indices, expiratory flow peak, exercise test, severity of dyspnea, and quality of life were evaluated as respiratory function parameters. Data analysis was done using SPSS software Version 16.Results:The mean maximum expiratory flow was significantly higher among cases who used morphine in comparison with the placebo group (p<0.05). Moreover, the severity of dyspnea, quality of life, and the frequency of coughing during the day were significantly improved among the recipients of morphine (p<0.05) while the spirometric indices and exercise tolerance tests were similar between the two groups (p>0.05), but the mean peak expiratory flow (PEFR) was significantly higher among the patients receiving morphine than the placebo patients (p<0.001).Conclusion:The use of inhaled morphine had a significant positive effect on the respiratory system of people exposed to mustard gas. We can use low doses of inhaled morphine to improve the respiratory function of these patients as a secondary therapy.

Heart Attack Risk Prediction with Duke Treadmill Score with Symptoms using Data Mining

The healthcare industry has a huge volume of patients’ health records but the discovery of hidden information using data mining techniques is missing. Data mining and its algorithm can help in this situation. This study aims to discover the hidden pattern from symptoms to detect early Stress Echocardiography before using Exercise Tolerance Test (ETT). During this study, raw ETT data of 776 patients are obtained from private heart clinic “The Heart Center Bahawalpur”, Bahawalpur, South Punjab, Pakistan. Duke treadmill score (DTS) is an output of ETT which classifies a patient’s heart is working normally or abnormally. In this work multiple machine learning algorithms like Support Vector Machine (SVM), Logistic Regression (LR), J.48, and Random Forest (RF) are used to classify patients’ hearts working normally or not using general information about a patient like a gender, age, body surface area (BSA), body mass index (BMI), blood pressure (BP) Systolic, BP Diastolic, etc. along with risk factors information like Diabetes Mellitus, Family History, Hypertension, Obesity, Old Age, Post-Menopausal, Smoker, Chest Pain and Shortness Of Breath (SOB). During this study, it is observed that the best accuracy of 85.16% is achieved using the Logistic Regression algorithm using the split percentage of 60-40.

Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure.

AimsRight ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV‐PA) predict cardio‐respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF).Methods and resultsThe Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV‐FAC), and RV myocardial performance index (RV‐MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end‐diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO2, minute ventilation/carbon dioxide production (VE/VCO2), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV‐PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II–III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO2 (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV‐FAC (β = 7.5), LAVi (β = −0.1), and sex (female, β = −1.9) predicted peak VO2 in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO2 (β = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO2 ≤ 14 mL/kg/min (0.39 for VO2 ≤ 12). RV‐MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO2) and 6MWD (β = 21.9 and β = −69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (β = −18.0 and β = 72.4, respectively, both P < 0.01), together with RV‐MPI (β = 18.5, P < 0.01) for VE/VCO2. Tricuspid regurgitation predicted SED (β = −3.2, P = 0.03).ConclusionsRight ventricular function assessed by echocardiography (RV‐MPI and RV‐FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV‐PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO2 and/or evaluation for advanced HF therapies.

Anti-ischemic effect and cardiodynamic changes under low-intensive laser irradiation compared to the obsidan effect in patients with angina pectoris

Purpose: to estimate the anti-anginal effect and to assess changes in hemodynamic parameters in patients with angina pectoris (AP) under low-intensive laser irradiation and to compare them with those under Obsidan preparation administration.Materials and methods. 70 males with AP of functional class I–IV were enrolled in the study and randomized into 2 equivalent groups: Group 1 – patients who took Obsidan; Group 2 — patients who were treated with infrared laser light. Patients were examined at the initial stage-one hour after 40 mg Obsidan take (Group 1), and one month after 10-day course of laser therapy (LT) (Group 2). All patients had echocardiography and cycle ergometric test.Results. The performed examinations showed a statistically significant increase in exercise tolerance in patients of LT group and Obsidan group by 35.0% and 34.1%, respectively. It should be noted that echocardiographic indicators had unidirectional, statistically significant shifts characterized by improvements in the myocardial inotropic function: decrease in the end-systolic volume by 17.9% and 18.8%, increase in the left ventricular ejection fraction from 50.3 ± 6.2 to 55.7 ± 5.8% and from 46.3 ± 4.3 to 50.1 ± 6.1 after LT and Obsidan , respectively. The optimal diastolic cardiac function was confirmed by the reduced time of myocardium isometric relaxation from 112.9 ± 24.3 to 94.3 ± 25.3 ms (p=0.012) under LT and from 110.3 ± 22.7 to 97.3 ± 19.3 ms under Obsidan (p=0.012). Results of the exercise tolerance test indicated the activation of cardiac economy mechanisms in both groups.Conclusion. Low-intensive LT had an impact at the cardiac activity similar to that of Obsidan. Moreover, it also has the equal anti-ischemic effect what may be explained by the decrease of energy expenditure during physical activity in patients with AP.

Abstract 13471: HFpEF in Spontaneously Obese Mice Due to Genomic Rearrangement in Non-Coding Region of Chromosome 1

Background: Obesity is the most common comorbidity and risk factor for heart failure (HF) in patients with preserved ejection fraction (HFpEF), a subclass containing more than 50% of HF cases. However, effective treatment of HFpEF remains scarce due to the incomplete understanding of the mechanisms. Methods: A mouse line (C57/B6J) of Floxed-stop Overexpression of IF1 (FEI) was generated and maintained for Cre-mediated conditional IF1 overexpression. We observed that severe obesity became a fixed phenotype in inbred FEI mice after inbreeding for 5-6 generations. Targeted-Locus-Amplification (TLA) analyses revealed that FEI inbreeding triggered a genomic rearrangement in a non-coding region of chromosome 1. A heterozygous line with genotype and phenotype fixation was obtained via outbreeding with wild type mice. In the present study, we focus on assessing the cardiac phenotype of FEI mice using echocardiography, histology, and exercise tolerance tests. Results: The early onset of obesity was consistent in the heterozygotes of obese FEI mice with increased peripheral fats and circulating tissue lipids, as well as reduced systemic metabolic rates. FEI mice also exhibited increased food intake, fasting blood glucose, insulin, and leptin with impaired glucose/insulin tolerance. Echocardiography revealed that the FEI mice developed concentric left ventricular hypertrophy with preserved ejection fraction. However, E/A ratio results from Doppler flow measurement at mitral valve suggest diastolic dysfunction in the FEI mice. Heart weight to tibial length ratio was significantly increased in FEI compared with WT mice. H&amp;E and Trichrome blue staining on heart sections exhibited increased cardiomyocyte hypertrophy and cardiac fibrosis. Treadmill exercise tolerance test revealed a significantly decreased exercise tolerance in FEI mice. Conclusions: We conclude that the cardiac phenotypes in the obese FEI mice closely recapitulate obese patients who suffer from HFpEF. Thus, further studies on these mice should yield novel and translational insight into the molecular and metabolic mechanisms underlying the HFpEF development, leading to improved treatments.

Histological and haemodynamic characterization of right ventricle in sedentary and trained rats with heart failure with preserved ejection fraction.

What is the central question of this study? Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF), nearly doubling the risk of death: what are the RV functional and structural changes in HFpEF and how does aerobic exercise impact them? What is the main finding and its importance? The HFpEF ZSF1 rat model presents RV structural and functional changes mimicking the human condition. Aerobic exercise prevented the decline in , lowered surrogate markers of RV overload (e.g., higher mean and maximum systolic pressure) and improved diastolic dysfunction (e.g., end-diastolic pressure and relaxation time constant). This emphasizes the importance of using exercise to manage HFpEF. Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF) and is a marker of poor prognosis. We assessed the obese ZSF1 rat model of HFpEF to ascertain if these animals also develop RV dysfunction and evaluated whether aerobic exercise could prevent this. Obese ZSF1 rats were randomly allocated to an aerobic exercise training group (n=7; treadmill running, 5days/week, 60min/day, 15m/min for 5weeks) or to a sedentary group (n=7). We used lean ZSF1 rats (n=7) as the control group. After 5weeks, rats were submitted to an exercise tolerance test and invasive haemodynamic evaluation, killed and samples from the RV collected for histological analysis. Obese sedentary ZSF1 rats showed lower , RV pressure overload (e.g., higher mean and maximum systolic pressure) and diastolic dysfunction (e.g., higher minimum and end-diastolic pressure and relaxation time constant), paralleled by RV cardiomyocyte hypertrophy. Except for cardiomyocyte hypertrophy, aerobic exercise prevented these functional changes. Our data support that this model of HFpEF shows functional and structural changes in the RV that resemble the human HFpEF phenotype, reinforcing its utility to understand this pathophysiology and to adress novel therapeutic targets to manage HFpEF. In addition, we showed that aerobic exercise is cardioprotective for the RV. A deeper knowledge of the mechanisms underlying the benefits of aerobic exercise could also lead to the identification of therapeutic targets to be further explored.

Aerobic exercise training prevents skeletal myopathy by myomiRs regulation in heart failure

Abstract Introduction Heart failure (HF) is the endpoint of systemic arterial hypertension. Exercise intolerance is a common symptom, partly due, to changes in the skeletal muscle mass (SM) and fiber type profile. Otherwise, aerobic exercise training (ET) has been used as an important non-pharmacological therapy in HF. MyomiRs are a muscle-specific class of miRNAs, which regulate genes that inhibiting the expression of proteins in pathological and physiological conditions controlling phenotypic changes in the SM, however little is known about these changes in ET-induced HF Purpose To elucidate the molecular mechanisms of ET involved in the metabolic alterations of SM in HF rats of hypertensive etiology. Methods The study was approved by the animal ethics committee (USP-No. 2020/01). 20 male rats, spontaneously hypertensive (SHR), and 10 Wistar Kyoto rats (WKY), SHR controls, nine-months-old, were divided into three groups: sedentary WKY (WKY-S), sedentary SHR (SHR-S), and trained (SHR-T). The ET consisted of swimming sessions with 60 minutes, 1x/day, 5x/week, for 10 weeks, with 5% of body overload. After ET protocol, blood pressure (BP), cardiac morphology and function (Echocardiography), exercise tolerance test, maximal oxygen uptake (VO2 peak), mitochondrial oxygen consumption (Oroboros), immunohistochemistry of the SM, expression of miRNAs (RT-qPCR) were evaluated. Statistical analyzes were performed by one-way ANOVA followed by the Tukey test. The results were expressed as mean ± standard error. Results ET reduced blood pressure levels and cardiac dysfunction in SHR-T compared to SHR-S. The SHR-S group covered smaller distance in the exercise tolerance test (255±22 meters) compared to the WKY-S (419±19 meters, p&amp;lt;0.0001), however ET reestablished the exercise tolerance (SHR-T: 365±20 meters; SHR-S: p&amp;lt;0.001 and WKY-S: p&amp;gt;0.05). The HF induced changes in type I and II fibers composition (I: 73±0.6% and II: 24±0.9%), VO2 peak (50±1.5 mL kg–1 min–1), mitochondrial oxygen consumption (State 3: 3.0±0.2 nmol O2 min–1 mg protein–1) and myomiRs expression (miRNA-208b: 65±4%, -499: 73±5%, -1: 153±10%) in the soleus muscle of SHR-S compared to WKY-S (I: 94±0.6%, II: 6±0.6%, p&amp;lt;0.001; VO2 peak: 59±2.3 mL kg–1 min–1, p&amp;lt;0.01; State 3: 4.0±0.2 nmol O2 min–1 mg protein–1, p&amp;lt;0.05; miRNAs: p&amp;lt;0.01). ET minimized changes in metabolic profile by counteract the muscle fiber type switching, and the oxygen consumption impairment, and myomiRs expression dysregulation (I: 90±0.5%, II: 9±0.6%, SHR-S p&amp;lt;0.01; VO2 peak: 79±2.4 mL kg–1 min–1, SHR-S: p&amp;lt;0.0001; State 3: 5.45±0.32 nmol O2 min–1 mg protein–1, SHR-S: p&amp;lt;0.0001; miRNA-208b: 91±5%, -499: 106±8%, -1: 100±9%; SHR-S: p&amp;lt;0.01). Conclusions ET reestablished structural and metabolic changes in SM, resulting from the progression of HF, through the regulation of myomiRs, improving exercise tolerance. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Coordination for the Improvement of Higher Education Personnel (CAPES): Academic Excellence Program (Proex).

Altered spatio-specific CaMKII activation in autophagy deficient mice

Abstract Background Autophagy is linked to preventing the development of cardiac hypertrophy and failure. While aberrant activation of Ca2+/calmodulin-dependent kinase II (CaMKII) promotes myocardial remodeling, the role of autophagy in maintaining cardiac Ca2+ homeostasis and regulating CaMKII signaling is unknown. Objective To test whether loss of autophagy promotes subcellular alterations in CaMKII activation in early myocardial remodelling, and whether compromised in vivo cardiac function parallels those changes. Methods Young (10–15 weeks) cardiomyocyte-specific autophagy protein 5-deficient mice (Atg5−/−) mice and their littermate controls (Atg5+/+) underwent comprehensive in vivo phenotyping using echocardiography, exercise tolerance and hemodynamic stress testing. In vitro assessment included gravimetry, qPCR of hypertrophy marker genes and cellular and nuclear dimensions of isolated ventricular myocytes. CaMKII activation was studied by immunocytochemistry in cardiomyocytes upon exposure to basal (1Hz) or high (4Hz) pacing frequency. Autophosphorylated CaMKII (pT286) signal was evaluated in different subcellular spaces (i.e. cytoplasm, nucleoplasm and nuclear envelope). Results Before symptomatic cardiac dysfunction occurred, Atg5−/− mice showed compromised cardiac reserve in response to β-adrenergic stimulation (dp/dt max: 9475±126 vs 7364±496 mmHg/s, N=4–5; p=0.041), despite similar maximum heart rate. Consequently, effort intolerance (distance run: 251±22 vs 152±13 m, N=8; p=0.03) and maximal oxygen consumption (2093±66 vs 1763±131 ml/h/kg, N=8; p=0.04) were reduced during treadmill exercise tolerance testing. Increased heart-to-body weight ratio (8.1±0.5 vs 10.2±0.8 N=9; p=0.017) was associated with elevated mRNA expression of hypertrophy marker NppB (278% of Atg5+/+, N=5; p=0.016) in Atg5−/− mice, which showed enlarged cardiomyocytes and nuclei, as width-to-length ratio. Because Atg5−/− cardiomyocytes exhibit elevated nuclear Ca2+ levels at high pacing frequency, we now measured subcellular CaMKII activation under the same experimental conditions. Interestingly, at 1Hz, p-CaMKII was increased specifically at the nuclear envelope (154% of Atg5+/+, N=5 mice, 153–159 cells; p=0.029), but not in the cytoplasm or nucleoplasm. Increasing pacing frequency to 4Hz did not alter p-CaMKII levels in Atg5+/+ cells. However, p-CaMKII was increased by ∼30% and ∼20% in the cytoplasm and nucleoplasm of Atg5−/− cells respectively (N=5 mice, 153–155 cells). Conclusion Loss of ATG5-dependent autophagy causes cardiac hypertrophy and impaired cardiac reserve upon acute stress, which involves CaMKII activation, likely through the imbalance of nuclear Ca2+ load. Although, selective increase in p-CaMKII at the nuclear envelope in Atg5−/− mice may temporarily protect from nuclear Ca2+ overload, excessive CaMKII activation in the cytoplasm and the nucleoplasm upon increased workload, likely drives hypertrophic signalling toward heart failure in autophagy-defective mice. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund (FWF)

Influence of resistance exercise on cardiac remodeling and soleus muscle of infarcted rats

Abstract Introduction Resistance exercise (RE) provides several benefits for healthy individuals. However, its effects during heart failure are unclear. The aim of this study was to evaluate the effects of RE on functional capacity, cardiac remodeling, and soleus muscle molecular and biochemical features in rats with myocardial infarction (MI). Methods Three months after MI or simulated surgery (Sham), Wistar rats were divided into three groups: Sham (n=14), MI (n=13), and MI subjected to RE (RE-MI, n=14). Exercised rats trained 3 times a week performing four climbs with progressive loads on a ladder over 12 weeks. Functional capacity was assessed by maximum carrying capacity test in the ladder and exercise tolerance test in treadmill. Echocardiogram was performed at the end of the study. Energy metabolism and antioxidant enzyme activities were assessed by spectrophotometry in the soleus muscle. Oxidative stress markers were analyzed in soleus muscle (lipid hydroperoxide) or serum (malondialdehyde and protein carbonylation). Protein expression of insulin type-1 growth factor-like pathway, protein kinase B, and rapamycin target complex was analyzed by Western-blot. Statistical analysis: ANOVA and Bonferroni or Dunn, Student's t and Goodman tests; p&amp;lt;0.05. Results Mortality was higher in MI than Sham. Infarction size did not differ between groups. Resistance exercise increased maximum load carrying capacity, without changing functional capacity or cardiac remodeling. Catalase activity was lower in MI than Sham and glutathione peroxidase activity was lower in MI than Sham and RE-MI. Protein carbonylation was higher in RE-MI than MI. Energy metabolism did not differ between groups, except for lower phosphofructokinase activity in RE-MI than MI. Expression of p70s6K, p-FoxO3a, and p-FoxO3a-to-FoxO3a ratio was lower, and p-p70s6K-to-p70s6K ratio was higher in MI than Sham. Conclusion The practice of resistance exercise is safe, attenuates mortality, and improves maximum load carrying capacity regardless of changes in cardiac remodeling in infarcted rats. In soleus muscle, resistance exercise preserves phosphofructokinase and antioxidant enzyme activity and expression of the proteins involved in muscle trophism. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CNPq UNESP

Cardiorespiratory function of patients undergoing surgical correction of Scheuermann's hyperkyphosis

The aim of this study was to analyze the impact of surgical correction of the thoracic deformity on the cardiorespiratory function of patients with moderate-severe Scheuermann’s hyperkyphosis (SK). A series of 23 adolescents with SK who underwent surgery through an only posterior approach using all pedicle screw constructs were included in the study. Cardiorespiratory parameters were measured during a maximal exercise tolerance test before and 2 years after surgery. Heart rate, oxygen saturation (SatO2), maximum oxygen uptake (VO2 max), ventilatory capacity at maximal exercise (VEmax), and energy costs were recorded. There were statistically significant differences in the forced vital capacity (FVC) (P < 0.05), total VO2max (ml/min) (P < 0.01), maximum expired volume (VEmax) per minute (P < 0.01) and cardiovascular efficiency (HR/VO2 ratio) (P < 0.05). None of these changes were clinically relevant. There were no changes in the VO2max per kg of body mass. The magnitude of the kyphosis correction did not correlate with the change in normalized VO2max or VEmax. In conclusion, patients with moderate-severe SK improve their baseline respiratory limitations and the tolerance to maximum exercise 2 years after surgery. However, the slight cardiorespiratory functional improvements should not necessarily be attributed to the surgery, and could also be caused solely by the residual growth of the lungs and thorax. Furthermore, respiratory functional changes are under thresholds considered as clinically relevant.

Spectrum of clinical applications of interlead ECG heterogeneity assessment: From myocardial ischemia detection to sudden cardiac death risk stratification.

Heterogeneity in depolarization and repolarization among regions of cardiac cells has long been recognized as a major factor in cardiac arrhythmogenesis. This fundamental principle has motivated development of noninvasive techniques for quantification of heterogeneity using the surface electrocardiogram (ECG). The initial approaches focused on interval analysis such as interlead QT dispersion and Tpeak–Tend difference. However, because of inherent difficulties in measuring the termination point of the T wave and commonly encountered irregularities in the apex of the T wave, additional techniques have been pursued. The newer methods incorporate assessment of the entire morphology of the T wave and in some cases of the R wave as well. This goal has been accomplished using a number of promising vectorial approaches with the resting 12‐lead ECG. An important limitation of vectorcardiographic analyses is that they require exquisite stability of the recordings and are not inherently suitable for use in exercise tolerance testing (ETT) and/or ambulatory ECG monitoring for provocative stress testing or evaluation of the influence of daily activities on cardiac electrical instability. The objectives of the present review are to describe a technique that has been under clinical evaluation for nearly a decade, termed “interlead ECG heterogeneity.” Preclinical testing data will be briefly reviewed. We will discuss the main clinical findings with regard to sudden cardiac death risk stratification, heart failure evaluation, and myocardial ischemia detection using standard recording platforms including resting 12‐lead ECG, ambulatory ECG monitoring, ETT, and pharmacologic stress testing in conjunction with single‐photon emission computed tomography myocardial perfusion imaging.