Bruce Protocol Research Articles

Effects of Different Endurance Training Models on Players’ Fitness Levels during the National Break in the Football Season

Purpose: This pilot study aims to determine the effects of different endurance exercises, during the 14-day national break during the football season. Methods: Four groups were formed randomly from 44 male football players (age 17-19 years old, stature 179.0±6.16 cm, body mass 70.4±5.53 kg, and body fat ratio 10.6±2.18 %) who regularly train and compete in the youth category of a football team: Small-Sided Games (SSG, n=10), Large-Sided Games (LSG, n=18), Running Without the Ball (RWB, n=8), and Control group (CG, n=8). VO2max (30-15 IFT and Bruce Protocol), balance (Y test), 10-20-30 m sprint, and T-test before and after the 14-day national break during the football season were measured. Heart rate and rate of perceived exertion (RPE) followed during the training program. Results: Significant differences were found in SSG (P= .001) and LSG (P= .005) in 30-15 IFT test (P< .05). In the Y-balance test, a statistically significant difference was found in SSG (P= .001) and LSG (P= .001) only. Conclusions: As a result, coaches are recommended to apply one of the RWB, SSG, or LSG training in addition to their routine football periods.

The effects of two different fatigue protocols on movement quality during anticipated and unanticipated change of directions in female soccer players.

This study compared neuromuscular control under two fatigue protocols during anticipated and unanticipated change of direction (COD) maneuvers and evaluated their effects on the risk of non-contact ACL injuries. Forty-five female soccer players (mean age: 22.22 ± 2.24 years; mean height: 166.24 ± 3.33 cm; mean mass: 59.84 ± 5.03 kg) were divided into three groups: functional fatigue (Soccer specific fatigue ptotocol-SOFT90), non-functional fatigue (Bruce protocol), and control group. Before and after the implementation of neuromuscular control fatigue protocols were evaluated using the cutting motion assessment score tool (CMAS). Two-dimensional (2D) videos were recorded during anticipated and unanticipated COD trials for both dominant and non-dominant legs. Significant time effects (p < 0.05) and group-time interactions (p < 0.05) were observed in both anticipated and unanticipated conditions for both dominant and non-dominant legs after the fatigue protocols. The functional fatigue group exhibited higher CMAS changes, indicating poorer movement quality following fatigue. Notably, the non-dominant leg displayed amplified deficits during unanticipated COD maneuvers following the functional fatigue protocol. Fatigue significantly impairs neuromuscular control, particularly in unanticipated COD situations, which increases the risk of non-contact ACL injuries. To mitigate this risk, coaches, trainers, and medical professionals should prioritize targeted training and injury prevention strategies, focusing on the non-dominant leg during unanticipated COD maneuvers.

Rating of Perceived Exertion Associated With Acute Symptoms in Athletes With Recent SARS-CoV-2 Infection: Athletes With Acute Respiratory InfEction (AWARE) VI Study.

SARS-CoV-2 infection can affect the exercise response in athletes. Factors associated with the exercise response have not been reported. To (1) describe heart rate (HR), systolic blood pressure (SBP), and rating of perceived exertion (RPE) responses to exercise in athletes with a recent SARS-CoV-2 infection and (2) identify factors affecting exercise responses. Cross-sectional, experimental study. Male and female athletes (age = 24.2 ± 6.3 years) with a recent (<28 days) SARS-CoV-2 infection (n = 72). A COVID-19 Recovery Clinic for athletes. Heart rate, SBP, and RPE were measured during submaximal exercise (modified Bruce protocol) at 10 to 28 days after SARS-CoV-2 symptom onset. Selected factors (demographics, sport, comorbidities, preinfection training variables, and symptoms during the acute phase of the infection) affecting the exercise response were analyzed using random coefficient (linear mixed) models. Heart rate, SBP, and RPE increased progressively from rest to stage 5 of the exercise test (P = .0001). At stage 5 (10.1 metabolic equivalents), a higher HR and a higher SBP during exercise were associated with younger age (P = .0007) and increased body mass index (BMI; P = .009), respectively. Higher RPE during exercise was significantly associated with a greater number of whole-body (P = .006) and total number (P = .004) of symptoms during the acute phase of infection. A greater number of symptoms during the acute infection was associated with a higher RPE during exercise in athletes at 10 to 28 days after SARS-CoV-2 infection. We recommend measuring RPE during the first exercise challenge after infection, as this may indicate disease severity and be valuable for tracking progress, recovery, and return to sport.

Анализ функций миокарда по данным Стресс-эхокардиографии при безболевой ишемии миокарда

The purpose — to analyze the results of stress-EchoCG in patients with and without silent myocardial ischemia (SMI). Material and methods. Results of stress-EchoCG of 202 patients during exercise test (ET) on treadmill according to Bruce protocol were analyzed. Results. Patients with SMI were 2.5 times more likely to achieve submaximal heart rate (p = 0.015) compared with the control group (CG). With the same exercise load, the maximum heart rate was higher in SMI group (p = 0.04). Maximum depression of ST segment was greater in SMI than in CG (p = 0.04). Dynamic of ST segment during ET was found in 75.6% subjects in SMI group and in 36.6% subjects in CG (p = 0.0001). Decrease in myocardial contractility during ET was 80.5% in SMI and 34.1% in CG (p = 0.0001). Combination of ST segment depression and contractility decrease was 56% in SMI and 9.2% in CG (p = 0.0001). In SMI, contractility decrease was found in 84.2% of segments. Conclusions. Decrease in contractility is higher in SMI than in CG. Positive ET with ST segment depression is more common in SMI. Depression of ST segment on positive ET was deeper in SMI than in CG. Negative test happens more often at SMI. Duration of ET in SMI was shorter due to rapid achievement of submaximal heart rate or ST segment depression. In SMI, ischemic manifestations occurred earlier and were more severe than in CG. Combination of segmental contractility disorders and ST segment depression in ET is a feature of myocardium in SMI.

Blood pressure reaction to treadmill test in normotensive Indian males with genetic risk of hypertension

Background: Studies have found that individuals with a genetic risk of hypertension may show an abnormal blood pressure (BP) reaction to various stressors and varied exercise protocols. Thus, these individuals may show an abnormal BP reaction in their daily activities. A submaximal exercise test usually mimics dynamic daily activities. This study was done to understand the BP reaction to the treadmill test in these individuals during incremental submaximal exercise testing. Aims and Objectives: The aims and objectives of the study are to compare BP reaction to treadmill test in healthy normotensive males with and without genetic risk of hypertension. Materials and Methods: A total of 100 healthy normotensive males between the age group of 35 and 45 years old took part in the study – fifty men with genetic risk of hypertension and 50 men without genetic risk of hypertension. The reaction of BP to exercise was done by treadmill test using submaximal Bruce protocol. The BP and pulse rate during rest, at the termination of each stage of the treadmill test, and during recovery were measured in each group. Data analysis was done using unpaired t-tests between the groups. Results: The systolic and diastolic BP were significantly increased during each stage of the treadmill test and during recovery in normotensive men with genetic risk of hypertension (P &lt; 0.001). Conclusion: Genetic risk of hypertension leads to increased BP reaction to exercise and during recovery in healthy normotensive males. Incremental exercise testing may have predictive value in recognizing individuals with a greater risk of developing systemic hypertension in the future.

Comparative study of treadmill test positive patients with coronary artery profile on coronary angiography in patient presenting with chest pain in BPKIHS, Dharan, Nepal

BACKGROUND Diagnosis of Coronary artery disease by Coronary artery angiography is limited by its availability, cost and as an invasive procedure. Treadmill test is a noninvasive and easily available test for diagnosing as well as prognosis of coronary artery disease and is most commonly performed stress test for diagnosis of coronary artery disease. Treadmill test is often used as an initial assessment of patient with suspected coronary artery disease serving as a poor man’s angiogram METHODS This was a cross sectional observational study carried out over a period from 25th August 2023 to 25th November 2023 in Department of Cardiology. A total of 100 patients with positive Treadmill test underwent CAG and subsequently analyzed for the presence of CAD were enrolled in the study. TMT test was done using Bruce Protocol and results were classified as positive and negative upon ECG changes. Data about Socio demographic profiles, clinical data, major comorbidity, the presumed risk factor for CAD were entered in MS Excel and analyzed through SPSS 25. RESULTS A total of 100 patients were enrolled in the study. Males were 45(45%) and females were 55(55%). The mean age of the patient was 53.38±16.7 years and 44.27±13.8 years in male and female group respectively. Smoking (82%) was the number one risk factor in male group and Hypertension (52%) in female group.. Significant CAD was seen in 33% of cases ad normal coronaries in 45%. The most common coronary artery involved having significant disease during coronary angiogram was LAD in 25% of cases CONCLUSIONS There was a significant correlation between positive TMT Results and coronary artery disease in coronary angiography.

Evaluation of Oxygen Consumption at Maximal Workload in Cases of Post-Covid-19 Syndrome.

Abstract:&#x0D; Objective:&#x0D; Oxygen consumption at maximal workload (VO2 max) is one of the important physiological criteria of endurance that has been used for many years and expresses aerobic capacity. In Post-Covid-19 Syndrome, some complaints persist for at least 12 weeks after the acute phase of SARS-CoV2 disease has passed. By comparing VO2max values and heart rate index values, it is aimed to verify whether aerobic capacity is affected in PCS.&#x0D; Methods:&#x0D; Between January and March 2021, 27 patients who were sent to scintigraphy for the evaluation of myocardial perfusion in terms of coronary artery disease due to chest pain and shortness of breath were included in the study. 11 of the patients were female. Treadmill exercise was applied to our patients by the Bruce Protocol procedure. All of our patients achieved 100% of the cardiac rate calculated with the 220-age formula. Our patients’ VO2max and HRI values before Covid-19 infection and after Post-Covid-19 syndrome diagnosis were compared.&#x0D; Results:&#x0D; Eleven (40.7%) of the cases were female. The median age of the patients was 53. The VO2max and HRI values calculated before the Covid-19 infection in our patients with PCS were higher than the later calculations. VO2max and HRI values were significantly decreased in patients who had Covid-19 infection and whose complaints were prolonged after the end of the acute phase. According to our findings, aerobic capacity decreased in our PCS patients. &#x0D; Conclusion:&#x0D; Complaints of PCS are accompanied by a decrease in aerobic capacity. Identifying the cause of the symptoms will enable us to develop new methods of prevention and treatment. VO2max and HRI values can be used in patient follow-up in PCS. Prospective studies are needed on this subject.

Deep learning-based dynamic ventilatory threshold estimation from electrocardiograms

Background and objectiveThe ventilatory threshold (VT) marks the transition from aerobic to anaerobic metabolism and is used to assess cardiorespiratory endurance. A conventional way to assess VT is cardiopulmonary exercise testing, which requires a gas analyzer. Another method for measuring VT involves calculating the heart rate variability (HRV) from an electrocardiogram (ECG) by computing the variability of heartbeats. However, the HRV method has some limitations. ECGs should be recorded for at least 5 minutes to calculate the HRV, and the result may depend on the utilized ECG preprocessing algorithms. MethodsTo overcome these problems, we developed a deep learning-based model consisting of long short-term memory (LSTM) and convolutional neural network (CNN) for a lead II ECG. Variables reflecting subjects' physical characteristics, as well as ECG signals, were input into the model to estimate VT. We applied joint optimization to the CNN layers to generate an informative latent space, which was fed to the LSTM layers. The model was trained and evaluated on two datasets, one from the Bruce protocol and the other from a protocol including multiple tasks (MT). ResultsAcceptable performances (mean and 95% CI) were obtained on the datasets from the Bruce protocol (−0.28[−1.91,1.34] ml/min/kg) and the MT protocol (0.07[−3.14,3.28] ml/min/kg) regarding the differences between the predictions and labels. The coefficient of determination, Pearson correlation coefficient, and root mean square error were 0.84, 0.93, and 0.868 for the Bruce protocol and 0.73, 0.97, and 3.373 for the MT protocol, respectively. ConclusionsThe results indicated that it is possible for the proposed model to simultaneously assess VT with the inputs of successive ECGs. In addition, from ablation studies concerning the physical variables and the joint optimization process, it was demonstrated that their use could boost the VT assessment performance of the model. The proposed model enables dynamic VT estimation with ECGs, which could help with managing cardiorespiratory fitness in daily life and cardiovascular rehabilitation in patients.

The cardiovascular response to exercise in athletes recovering from SARS-CoV-2 infection: A prospective cohort study with repeated measures over 16 weeks – AWARE IX

ABSTRACT Higher exercise heart rate (HR) and prolonged return-to-sport in athletes with SARS-CoV-2 infection are described, but the cardiovascular response to exercise during recovery is not understood. This prospective, cohort, experimental study with repeated measures evaluated the cardiovascular response to exercise over 16 weeks in athletes recovering from SARS-CoV-2 infection. Athletes (n = 82) completed 2–5 repeat assessments at regulated intervals over 16 weeks post-SARS-CoV-2 infection. Data from 287 assessments (submaximal exercise tests; Modified Bruce protocol) are included. HR (bpm), systolic blood pressure (SBP) (mmHg) and rating of perceived exertion (RPE) (Borg scale 6–20) were measured. Rates of change in HR, SBP and RPE over time are reported. Submaximal exercise HR, SBP and RPE decreased significantly over 16 weeks (p < 0.01). There was a steeper rate of decline for HR and RPE ≤30 days compared to >30 days after SARS-CoV-2 infection: HR at Stage 3: ≤30 days −0.53 (0.01); >30 days −0.06 (0.02) and Stage 5: ≤30 days −0.77 (0.12); >30 days −0.12 (0.02); RPE at Stage 3: ≤30 days −0.09 (0.02); >30 days −0.01 (0.0002) and Stage 5: ≤30 days −0.13 (0.02); >30 days −0.02 (0.004). The findings provide clinical recommendation for exercise prescription and monitoring RPE in response to exercise post-SARS-CoV-2 infection and contribute to the clinical understanding of recovery which can help manage athlete expectations.

A Reference Equation for Peak Oxygen Uptake for Pediatric Patients Who Undergo Treadmill Cardiopulmonary Exercise Testing

Pediatric patients are often referred to cardiopulmonary exercise testing (CPET) laboratories for assessment of exercise-related symptoms. For clinicians to understand results in the context of performance relative to peers, adequate fitness-based prediction equations must be available. However, reference equations for prediction of peak oxygen uptake (VO2peak) in pediatrics are largely developed from field-based testing, and equations derived from CPET are primarily developed using adult data. Our objective was to develop a pediatric reference equation for VO2peak. Clinical CPET data from a validation cohort of 1,383 pediatric patients aged 6 to 18years who achieved a peak respiratory exchange ratio ≥1.00 were analyzed to identify clinical and exercise testing factors that contributed to the prediction of VO2peak from tests performed using the Bruce protocol. The resultant prediction equation was applied to a cross-validation cohort of 1,367 pediatric patients. Exercise duration, gender, weight, and age contributed to the prediction of VO2peak, generating the following prediction equation: (R2=0.645, p <0.001, standard error of the estimate=6.19ml/kg/min): VO2peak (ml/kg/min) =16.411+ 3.423 (exercise duration [minutes]) - 5.145 (gender [0=male, 1=female]) - 0.121 (weight [kg])+0.179 (age [years]). This equation was stable across the age range included in the present study, with differences ≤0.5ml/kg/min between mean measured and predicted VO2peak in all age groups. In conclusion, this study represents what we believe is the largest pediatric CPET-derived VO2peak prediction effort to date, and this VO2peak prediction equation provides clinicians who perform and interpret exercise tests in pediatric patients with a resource with which to better quantify fitness when CPET is not available.

Cigarette smoking abolishes the mediterranean diet benefit on exercise capacity, coronary physiology and target organ damage in hypertensive males with erectile dysfunction

Abstract Background Erectile dysfunction (ED) often coexists impairing quality of life in the hypertensive aging male population. The Mediterranean diet (Med-diet) benefits cardiovascular health. Coronary flow reserve (CFR) displays the ability of the coronary circulation to increase flow. Central vascular stiffness and microalbuminuria (UMALb) represent hypertension-related target organ damage (TOD). Purpose To investigate cigarette smoking adverse effects on the Med-diet benefit in exercise capacity, coronary physiology and TOD in hypertensive males with ED. Methods We enrolled 290 hypertensive ED males (mean age: 57 yo) with no history of diabetes mellitus or overt cardiovascular disease. 121 (42%) were current cigarette smokers. Intensity of smoking referred in packs/year. All underwent a treadmill stress test (Bruce protocol), exercise capacity was validated as metabolic equivalents (METs). We measured the CFR of the LAD artery (2D echo) by performing an adenosine protocol (max dose 140μg/Kg/min over 6 min). PW Doppler measurements were achieved at the middle/distal LAD (color Doppler flow mapping). CFR was validated as ratio between peak diastolic flow velocity following drug infusion and rest. Ratios ≥ 2 indicate macro and microvascular coronary integrity. Participants were screened for the presence of UMALb (urinary albumin loss 30 – 300 mg /24 h urine volume collection). Finally a non-invasive evaluation of the carotid – femoral pulse wave velocity (PWV), estimation of central pressures and augmentation index (AIx) a parameter of wave reflection amplification were performed (Sphygmocor device). ED severity and the Med-diet adherence were assessed by the SHIM-5 (range:0-25) and the Med-diet (range:0-55) scores. Higher values indicate a better erectile ability and Med-diet compliance respectively. Results In bivariate analysis the Med-diet score was positively associated with METs, CFR and the SHIM-5 score and negatively with PWV, AIx and UMALb (p&amp;lt; 0,05). CFR, METs and the SHIM-5 score were also positively related (p&amp;lt; 0,03). In linear regression analysis the Med-diet relation remained significant after correction for age, BMI, LDL, total cholesterol and systolic blood pressure. However introducing cigarette smoking as a cofounder abolished the above relations. Packs/year were positively related to AIx, UMALb and negatively to the SHIM-5 score (p&amp;lt; 0,05). We also divided our population according to the mean Med-diet score (27) in high and low Med-diet groups .The high score group had higher METs and SHIM-5 score and lower PWV. Smokers had higher AIx and lower SHIM-5 score (pictures). Conclusion Cigarette smoking influences microvascular physiology and peripheral wave reflection and so abolishes Med-diet benefit on exercise capacity, coronary physiology, target organ damage and erectile ability in hypertensive males with ED. It is of vital importance consult this population avoiding smoking to restore cardiovascular health and quality of life.

Sex differences in individuals with high normal blood pressure who developed hypertension in three-year follow-up

Abstract Background Recent data demonstrated that females are at risk for cardiovascular disease at a lower blood pressure (BP) level than males. Purpose Identify normotensive individuals with high normal BP who are going to develop hypertension in three-year follow-up and demonstrate differences according to their gender. Methods 100 individuals with high normal BP were followed-up for 3 consecutive years. During enrolment they underwent ambulatory BP monitor (ABPM), electrocardiogram (ECG), echocardiogram, carotid-femoral pulse wave velocity (PWV), sympathetic drive assessed by muscle sympathetic nerve activity (MSNA), a negative for ischemia treadmill exercise stress test (TST) (Bruce protocol) and blood sampling. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in office and with ABPM. All participants offered lifestyle advise to lower their BP. Endpoint was development of hypertension (HTN). Results 19 males and 21 females developed HTN. Office and ABPM measurements did not differ significantly but women who developed HTN demonstrate higher pulse pressure 50vs45 mmHg (p=0.03). In ABPM systolic blood pressure (SBP) differ (123 vs 119 mmHg, p=0.01) in future hypertensive females. Additionally night-time SBP differ in both genders who were going to develop HTN (women: 116vs111 mmHg, p=0.007 and men: 116vs111 mmHg, p=0.043). Both genders demonstrate significantly different PWV values among future hypertensives and those who remained normotensives (women: 8.2vs7.2 m/s, p&amp;lt;0.001, men: 8.3vs7.2 m/s, p&amp;lt;0.001). Males and females who developed hypertension had higher sympathetic activity as reflected from MSNA levels (men: 33vs27 bursts/minute, p&amp;lt;0.001, women: 36vs28 bursts/minute, p&amp;lt;0.001). Both genders who developed HTN had higher SBP at peak exercise (men: 208vs184 mmHg, p&amp;lt;0.0001, women: 197vs173 mmHg, p&amp;lt;0.0001) as also steeper SBP/MET slope (men: 6.7vs5.0, p=0.038, women: 7.1vs3.8, p&amp;lt;0.0001), while their maximal heart rate achieved differ (men: 158bpm vs 167bpm, p=0.014, women: 153bpm vs 162bpm, p&amp;lt;0.0001). Only in women's baseline ECG who developed HTN had wider p-wave duration (103vs94ms, p=0.032) and QRS length (88vs80ms, p=0.018). While echocardiographicly they displayed increased left ventricular mass index (LVMI) (81vs72 g/m²,p=0.006), atrial diameter (37vs34 mm,p&amp;lt;0.0001) and decrease E/A ratio of transmitral flow velocity (0.8vs1.0, p=0.005). Kidney function assessed by 2021 CKD-EPI eGFR reveals a deterioration in those women who are going to develop HTN (87 vs 97 mL/min/1.73 m², p=0.009). Conclusions Both men and women benefit from treadmill exercise stress test as a prognostic tool that can reveal the likelihood of development of hypertension in both sexes and arouse the need to research for target organ damage in women who are in prehypertensive state and may benefit from an early intervention until clarify sex-specific thresholds for diagnosis of hypertension.

Performance-based outcome measures for physical capacity and functional ability among patients with pulmonary embolism

Abstract Introduction Pulmonary embolism (PE) is a serious health condition with up to 50 % of patients experiencing persisting symptoms with shortness of breath, pain, reduced physical performance and psychological distress, also known as post-PE syndrome. This condition has received increasing attention, including recommendations of assessing physical capacity to identify patients who may benefit from rehabilitation interventions to increase functional ability and health. However, as the PE population is heterogeneous compared to other cardiac patient groups, outcome measures for assessing physical capacity traditionally used in cardiac rehabilitation may not be reliable. This scoping review aims to map the performance-based outcome measures (PBOM) used in research literature to measure physical capacity in a PE population, to map the nature of the research and investigate the psychometric properties of the identified instruments in a PE population. Methods The methodology of the review process was guided by the Joanna Briggs Institute (JBI) framework for scoping reviews and reporting followed the PRISMA guidelines. Results The search identified a total of 4585 potentially relevant studies of which 234 studies met the inclusion criteria. A substantial part of studies (190 studies) was on a CTEPH population (chronic thromboembolic pulmonary hypertension), a condition developed by just 1-2% of patients with PE. The majority of included research articles originated from Europe (51%) and Asia (36%). Ten different PBOMs were identified for measuring physical capacity in a PE/CTEPH population, with 6MWT and CPET as the far most commonly used and the Bruce protocol/Modified Bruce protocol and Incremental Shuttle Walk test (ISWT) as third and fourth. No studies were identified reporting on psychometric properties of the 10 PBOMs in a PE / CTEPH population. Conclusions No studies were identified reporting on validity or reliability of any of the 10 identified PBOMs in a PE/CTEPH population. Thus, there is a need for conducting studies that establish the reliability, validity and responsiveness of PBOMs in a PE population, to enable identification of at-risk patients and to monitor effects of treatment and rehabilitation interventions.

Even the presence of minimal changes in regional wall motion abnormalities with exercise stress echocardiography predicts MACE and all-cause mortality in patients with previous chest radiotherapy

Abstract Background Exercise stress echocardiography (ESE) is a non-invasive, radiation-free, and widely available technique that has demonstrated a reliable accuracy for the detection of coronary artery disease (CAD). Chest radiotherapy (RT) is associated with accelerated age-related atherosclerosis and fibrosis in a dose-dependent manner. ESE plays a role as a screening tool of RT induced heart disease, however, the prognostic value of changes in regional wall motion abnormalities in this population during ESE has not been evaluated. Methods This is a retrospective cohort study of breast cancer survivors treated with adjuvant RT that underwent ESE from 2000-2020 after treatment completion. Outcomes evaluated were: major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, revascularization and stroke); and all-cause mortality. A univariate analysis was performed to characterize the population. Continuous variables were presented as means ± standard deviation (SD) or median with quartile 1 and 3 (Q1, Q3), and categorical variables as numbers and percentages. A Cox regression model adjusted by age and cardiovascular risk factors was used to evaluate variables associated with outcomes, and a time to first event approach was used. A p-value of &amp;lt;0.05 was considered statistically significant. Results From 2000-2020, 507 patients, with a mean age 66 ± 10 years, underwent ESE at a median of 5.8 years after RT completion. The most prevalent comorbidities were dyslipidemia (59%), HTN (55%) and obesity (37%). 55% underwent RT for left-sided breast cancer and 45% for right-sided, and median RT dose was 6000 cGy. Baseline characteristics are presented in Table 1. Most patients underwent Bruce Protocol (92%). Patients exercised a mean time of 6.6 minutes achieving 7.3 METS and 109% of functional aerobic capacity (Table 2). At a median follow up of 7.8 years, 61 MACE events occurred. Predictors of MACE were double product, baseline and stress EF, baseline and peak regional wall motion abnormalities (RWMA), development of new ischemic RWMA, inability to reach 85% of maximum HR, and an abnormal EF response with stress after adjusting for age, HTN, DM, smoking history, dyslipidemia, obesity, prior MI and cancer staging (Fig 1). Predictors of all-cause mortality were METS, LV mass index, baseline and peak RWMA, development of new ischemic RWMA and an abnormal EF change with stress even after adjusting for variables described previously (Fig 2). Conclusions The development of new or worsening RWMA of just 2 segments with stress, was a significant predictor of MACE and all-cause mortality in a large cohort of breast cancer survivors undergoing multidisciplinary management including adjuvant RT. Special emphasis on management of cardiovascular comorbidities and closer surveillance are recommended for these patients.

Comparison of pulse wave velocity and hypertensive response to exercise in predicting incidence of resistant hypertension

Abstract Background Resistant hypertension (RH) is strongly associated with occurrence of major cardiovascular events and death. Hypertensive response to exercise (HRE) and arterial stiffness estimated by peripheral pulse wave velocity (PWV) are surrogate markers of incident hypertension, whereas their role in predicting RH development remains uncertain. Purpose Explore the predictive role of PWV and HRE in incident RH. Methods A Comparison of HRE and PWV in predicting development of RH was performed in retrospective study with a cohort of 198 patients with known coronary artery disease (CAD). The patients performed two Bruce protocol stress tests (STs) between 01/2009 and 12/2022. The first ST was used to assess HRE and estimated PWV (ePWV) in predicting occurrence of apparent treatment-resistant hypertension (aTRH). ePWV was calculated using age and blood pressure, as previously described (1). HRE response was defined either as systolic BP (SBP) &amp;gt; 210 mmHg or difference between peak and baseline &amp;gt; 60mmHg for men (&amp;gt;190 mmHg or 50 mmHg in women) (2). aTRH was defined as resting SBP above 140mmHg in the last ST despite simultaneous use of ≥3 different antihypertensive agents. The average time between STs was 4±3 years. The incidence of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, heart failure and stroke) were analyzed during the follow-up period of 10±3 years. Logistic and Cox regression models were used in time-to-event analysis. Data presented as: mean ± standard deviation; 95% confidence interval (CI) for odds ratios (OR); significance between groups p&amp;lt;0.05. Results The incidence of aTRH between STs was 15% (n=30), with 48% of them (n=14) receiving ≥4 or more antihypertensive drugs. aTRH vs non-aTRH were similar at baseline for sex (89% male, p=0.67), hypertension (HT, 62%,p=0.08), dyslipidemia (79%, p=0.86), smoke (46%, p=0.50), chronic kidney disease (13%, p=0.39), myocardial infarction (75%, p=0.39), heart failure (4.5%, p=0.40), but not for body mass index (30±3 vs 28±3 kg/m2, p=0.012) and diabetes (60.0 vs 28.6%, p=0.003) that were higher in the aTRH group. The average ePWV was 9.3±1.6 m/s (9.14±1.5 vs 10.2±1.7 m/s, non-aTRH vs aTRH p=0.001); 22.6% patients had HRE (20.4% vs 36.0%, non-aTRH vs aTRH, p=0.084). In contrast to HRE (adjusted OR=1.34, CI 0.4-4.3, p=0.62), ePWV was correlated with aTRH (adjusted OR=2.0, CI 1.1-4.1, p=0.024) after adjusting for age, comorbidities and anti-HT drugs, with an area under the ROC curve of 0.7 (CI 0.6-0.8). Both aTHR (OR=2.6, CI 1.2-5.8, p=0.017) and ePWV (adjusted OR=1.3, CI 1.2-5.8, p=0.024) were associated with MACE. Conclusion ePWV is a simple and robust marker that outperforms HRE in predicting aTRH and MACE in CAD patients. Higher ePWV values were independently associated with the incidence of aTRH. This study strengthens the importance of developing new strategies to control arterial stiffness in the treatment of RH and prevention of MACE.

Rethinking the false positive exercise stress test in the context of coronary microvascular dysfunction

Abstract Background Exercise stress testing (EST) was the traditional tool to detect myocardial ischaemia, but its use has declined due to its perceived high false positive rate. However, EST was historically validated against the reference standard of obstructive coronary artery disease (CAD). It is now well recognised that myocardial ischaemia can occur in the absence of CAD and this cohort, termed angina with non-obstructive coronary arteries (ANOCA), comprises nearly 50% of all patients presenting with stable angina. Purpose Our study assesses the accuracy of EST in detecting a substrate for myocardial ischaemia, with the reference standard being comprehensive coronary physiology assessment in patients with ANOCA. Methods Patients with typical angina and non-obstructive coronary arteries underwent physiological characterisation of the coronary circulation using a dual sensor-tipped intracoronary guidewire in the left anterior descending artery. The epicardial vessel was assessed by Fractional Flow Reserve (FFR) and the microcirculation by both endothelium-independent function (coronary flow reserve, CFR, using intravenous adenosine) and endothelium-dependent function (acetylcholine flow reserve, AChFR, using intracoronary acetylcholine infusion). Those with FFR≤0.80 were excluded per protocol. Coronary microvascular dysfunction was defined a priori as impaired CFR (&amp;lt;2.5) or impaired AChFR (≤1.5). All patients underwent a treadmill EST, using a standard Bruce protocol, with ischaemic electrocardiographic (ECG) changes defined as the appearance of 0.1mV ST-segment depression 80 milliseconds from the J-point. Patients, physiologists, and researchers were all blinded to the coronary physiology data. All data are presented as mean±SD or median (IQR). Results Ninety-one patients [67% female, 62±9 years, CCS 3 (2 to 3)] were recruited into this study. EST was performed 27 (15 to 139) days after angiography. Twenty-seven patients (30%) developed ischaemic ECG changes during their EST (Ischaemic group), whereas 64 patients (70%) did not (Control group). Both groups were phenotypically similar for demographics, risk factors, exercise time and FFR (Figure 1). 100% of the Ischaemic group and 69% of the control group had CMD. Conversely, 38% of patients with CMD developed ischaemic ECG changes on exercise but none (0%) of those with normal microvascular function did (p=0.001) (Figure 2A). The false positive rates with progressively granular reference standards are depicted in Figure 2B; there were no false positive ESTs using a comprehensive physiological reference standard. Angina reported during EST was less specific for CMD than induced ECG changes (70% vs 100%, p&amp;lt;0.001). Conclusions In patients with ANOCA a positive EST is always indicative of CMD. The potential utility of EST as a rule-in test for CMD makes it an attractive non-invasive widely available test that could be re-integrated into clinical pathways for assessing new onset angina.Patient characteristicsEST versus coronary physiology

Impact of short-term exercise training on QT dispersion and double product in diabetic patients after surgical aortic valve replacement

Abstract Background QT dispersion (QTd) represents the heterogeneity in the repolarization of the ventricular myocardium and electrical instability of the myocardium, reflecting the increased tendency towards ventricular arrhythmias. Abnormally high QTd has been correlated with risk of cardiac death. Purpose The aim of this study was to establish the influence of short-term exercise training on QT dispersion and double product (DP), in diabetic patients after surgical aortic valve replacement (SAVR). Methods The study involved 147 patients after SAVR, in the sinus rhythm without AV blocks or branch blocks. Average age of patients was 59.3 years. 45 patients were with diabetes mellitus, and 102 were without diabetes. Patients were similar as to age and baseline stress test duration. In all subjects clinical examination, standard ECG and exercise test on treadmill according to Bruce protocol, were performed and after that patients were included in program of physical training for three weeks. Patients were instructed to follow a training program using the bicycle ergometer (10 min, 2 times a day), gymnastic exercises and walking. The patients continued to take the same medicaments in same doses. From standard ECG corrected QT dispersion (QTdc) was calculated. Results Before starting with the program of physical training, patients with diabetes had significantly higher values of QTdc (83.4 ± 15.3 vs 74.6 ± 16.9 ms; p&amp;lt;0.005) in comparison to those without diabetes. After three weeks, significant reduction of QTdc was found (from 83.4 ± 15.3 to 77.3 ± 15.4 ms; p&amp;lt;0.02 in patients with diabetes and from 74.6 ± 16.8 to 68.7 ± 17.1 ms; p&amp;lt;0.005 in patients without diabetes). After three weeks, significant reduction of DP was found (from 11763.8 ± 779.9 to 11314.8 ± 635.8 beat/min x mmHg; p&amp;lt;0.005 in patients with diabetes and from 114376.4 ± 792.3 to 10034.2 ± 521.3 beat/min x mmHg; p&amp;lt;0.001 in patients without diabetes). In diabetic patients, after program of physical training, significant reduction of glycemia was found (from 7.0 ± 2.3 to 5.9 ± 1.5 mmol/L; p&amp;lt;0.005), of total cholesterol from 5.2 ± 1.3 to 4.6 ± 1.1 mmol/L (p&amp;lt;0.025), of LDL cholesterol from 3.2 ± 0.8 to 2.8 ± 0.6 mmol/L (p&amp;lt;0.05). After three weeks, both groups of patients in the exercise test reached a significantly longer time (p&amp;lt;0.001). Conclusions The study showed that patients with diabetes have a higher value QTdc, probably due to diffuse interstitial fibrosis. Short-term exercise training has favourable effects on QT dispersion and double product in patients after SAVR. In patients without diabetes physical training had more favourable effects on the followed parameters. Physical training led to the significant decrease of myocardial oxygen uptake at rest and probably decreased the possibility of arrhythmia events.

Effect of arterial hypertension in cardiopulmonary status and right ventricle function after hospitalization for Sars-Cov-2

Abstract Introduction There is little data concerning the impact of SARS-Cov-2 infection on the cardiopulmonary status and right ventricle (RV) function of patients with arterial hypertension (HTN). Purpose The purpose of our study was to investigate whether hospitalization for COVID19 affects the functional status of hypertensive patients, using cardiopulmonary test and echocardiographic parameters, 3 months after the first day of infection. Methods All subjects underwent cardiorespiratory exercise using Bruce or modified Bruce protocol where all cardiorespiratory parameters were evaluated. Echocardiographic parameters including right ventricle longitudinal strain were analyzed using an offline program. Subjects with history of HTN were divided into two groups according to hospitalization for Covid-19 infection. Group I included 34 subjects who were hospitalized for Sars-Cov-2 infection and Group II included 28 subjects without need for hospitalization. Results Out of total population of 198 patients with COVID19 infection, sixty-two subjects were hypertensives (mean age: 61±10 years, 58.1 % males, history of coronary artery disease: 16.1%) who were evaluated 3 months after the symptoms onset. Of demographic characteristics in hospitalized patients, only age (63±8 vs. 52±11 years, p&amp;lt;0.001) was significantly higher. When analyzing cardiopulmonary test parameters, oxygen consumption (ml/kg/min) both maximum (21±4 vs. 23.5±4, p:0.01) and during the 1st minute of recovery (15.5±2 vs. 21±25, p: 0.02), VO2_AT (17±4 vs. 27.5±32) and PETCO2 (39±4 vs. 38±19 mmHg, p:0.03) were impaired comparing to non-hospitalized subjects. Out of echocardiographic parameters, diameter of left atrium (mm), differed significantly between two groups (41±6 vs.38±5 p: 0.02). The absolute mean value of right ventricle strain (RVLS, (%): 13±8 vs. 23±3, p:0.04) was impaired to hypertensives despite the fact that left ventricle ejection fraction was similar between two groups probably due to small sample size. Using linear regression analysis adjusted for age, gender, hospitalization, and LVEF, hospitalization (p: 0.001) proved to be independent predictive factor for RVLS in hypertensive patients. Conclusion To conclude our study highlighted negative impact of hospitalization for Sars-Cov-2 infection in the capacity for exercise and in right ventricle functionality, implying the severity of disease as a negative independent predictive factor in hypertensive patients.

Angiogenic gene therapy for refractory angina: results of the epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (EXACT) phase 2 trial

Abstract Background Refractory or "no option" angina (RA) is a debilitating condition with increasing global prevalence. Exogenous transduction of vascular endothelial growth factor (VEGF) induces angiogenesis and improves perfusion of ischemic myocardium in preclinical studies. XC001 (AdVEGFXC1) is a novel adenoviral-5 vector expressing the three major isoforms of VEGF (-121, -165, -189) in ratios shown to enhance potency and improve safety. Purpose EXACT is a single-arm, multicenter, open-label, phase 2 trial to explore the safety, tolerability, and preliminary efficacy of trans-epicardial delivery of XC001 to improve exercise capacity and ischemic burden in RA patients. Methods Patients were required to have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy with exercise limited by angina after 90 but before 540 seconds on a modified Bruce protocol, demonstrable ischemia on stress positron emission tomography (PET) and lack revascularization options. XC001 (1x1011 viral particles) was injected directly into ischemic myocardium via surgical transthoracic epicardial access. The primary outcome was safety by adverse event monitoring. Efficacy assessments included difference from baseline to six months in total exercise time (TET), myocardial ischemia by PET, angina class, angina frequency, and quality of life. Results Thirty-two patients (mean/median ages of 64/64, 34% female) were enrolled at 13 sites between March 2021 and July 2022. Median anti-anginal use was 3, 75% had prior revascularization with CABG and 88% with PCI. Fifty-five serious adverse events (SAEs) were observed in 21 patients (66%). None were attributed to study drug. Twenty-one SAEs in 14 patients were related to the surgical procedure, all of which were expected. One non-CV death occurred in month 3 following respiratory infection (Covid) deemed unrelated to surgery or study drug. Compared to baseline, total exercise time at 6-months increased by 85.5 seconds (95% CI 31.3-139.7) [Figure 1A] while total myocardial ischemic deficit in the treated region on PET decreased by 14.4% (95% CI, 3.01–25.73) [Figure 1B]. Angina frequency and nitroglycerin use measured during a two-week diary decreased by 6.6 episodes (95% CI, 3.5–9.7) and 4.1 doses (95% CI, 1.3–6.9), respectively. Canadian Cardiovascular Society angina grade decreased from 3.1 to 1.8, mean difference 1.3 classes (95% CI, 1.0–1.6) [Figure 2] while Seattle Angina Questionnaire Frequency score improved from 41.3 to 67.4, mean difference of 26.1 (95% CI, 16.3–35.9). Conclusions VEGF gene therapy with XC001 administered via minimally invasive epicardial delivery appears safe and well tolerated. Improvements in objective and subjective measures including total exercise time, myocardial perfusion, angina frequency and quality of life support a clinically meaningful biologic effect. This therapy warrants study in larger randomized studies.

Abstract 12142: Treadmill Exercise Stress Echocardiography Exposes Impaired Left Ventricular Function in Patients Recovering From Hospitalization for COVID-19 versus Historical Controls

Usual clinical testing rarely reveals persisting cardiac abnormalities in patients after hospitalization for Covid-19. Such testing may overlook residual changes responsible for increased adverse cardiac events seen post-discharge. To further elucidate patients’ long-term status, we performed exercise stress echocardiography (ESE) in 15 patients age 30-63 without myocarditis 3 to 31 months after hospital discharge. We compared patient outcomes to published data in healthy controls (HC) exercising according to the same protocol. Patients’ treadmill exercise (Bruce protocol), averaging 8.2 min, was halted by dyspnea or fatigue. Baselines before stress averaged the same in recovering patients (RP) and HC except for heart rate (HR): 81±13 bpm for RP and 63±8 for HC (p&lt;0.0001). Peak stress values in RP were compared with HC: Stress revealed significantly lower LVEF and raised E/e’ soon after peak effort in RP compared with HC performing the same exercise. Thus, when stressed, patients with no known cardiac impairment before or during Covid-19 hospitalization showed modest but consistently diminished systolic contractile function and diastolic LV compliance during recovery compared to HC. Peak HR during stress was significantly elevated in RP vs. HC; peak SBP also trended higher. Average systolic pulmonary artery pressures among RP remained normal. Our measurements during ESE uniquely identified residual abnormality in cardiac contractile function not evident in the unstressed condition. This finding exposes a previously-unrecognized residual influence of Covid-19 that may relate to underlying autonomic dysfunction, microvascular disease, or diffuse interstitial changes after subclinical myocarditis and may have long-term implications for clinical management and later prognosis.