Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

BACKGROUND: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. METHODS: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. RESULTS: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. CONCLUSION: In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

Cardiopulmonary testing in adult patients with ß-thalassemia major in comparison to healthy subjects.

ß-Thalassemia patients often have a reduced capacity of exercise and abnormal respiratory function parameters, but the reasons are unclear. In order to identify the causes of the exercise limitation, we performed a cardiopulmonary exercise testing (CPET) in a group of 54 adult ß-thalassemia major (TM) patients without pulmonary arterial hypertension and in a group of healthy control subjects. All subjects underwent cardiac echocardiography and carried out pulmonary function tests. TM patients also filled an IPAQ questionnaire on usual physical activity (PA).Overall, TM patients have a diminished exercise performance in comparison to control subjects. In fact, peak oxygen uptake (V'O2 peak), expressing maximum exercise capacity, was decreased in 81.5% of the patients; similarly, anaerobic threshold (V'O2@AT) and O2 pulse also resulted lowered. In multivariable regression models adjusted for gender, age, BMI, and mean haemoglobin, V'O2 peak and O2 pulse were positively associated with cardiac iron overload (T2*). No ventilatory limitation to exercise was observed. The most important causes of exercise limitation in these patients were muscular deconditioning and reduced cardiac inotropism due to iron deposition. Only 15/54 (27.8%) TM patients used to perform vigorous physical activity. These results suggest that a program of regular physical activity may be useful to increase the tolerance to effort and therefore to improve the quality of life in these patients.

Effects of High Intensity Interval Training Rehabilitation Protocol after an Acute Coronary Syndrome on Myocardial Work and Atrial Strain.

Background andObjectives: Current guidelines on cardiac rehabilitation (CR) suggest moderate-intensity physical activity after acute coronary syndrome (ACS). Recent report have shown that high-intensity interval training (HIIT) could be more effective than moderate-intensity continuous training (MCT) in improving cardiac performance. Our aim was to analyze the effects of HIIT protocol after ACS on advanced echocardiographic parameters of myocardial function. Materials and Methods: In total, 75 patients with recent ACS, with or without ST segment elevation, were enrolled and compared with a control group of 50 age- and sex-comparable healthy subjects. Patients were randomized to perform a MCT training or HIIT-based rehabilitation program. A complete echocardiographic evaluation, including left ventricular (LV) and left atrial (LA) global longitudinal strain (GLS) and myocardial work (MW) through speckle-tracking analysis, was performed for all patients, before and after cardiac rehabilitation training. A cardiopulmonary exercise testing (CPET) was also performed at the end of the rehabilitation program. Results: Patients who followed the HIIT rehabilitation program showed improved LV diastolic function compared to the MCT group (E/e': 3.4 ± 3.1 vs. 6.4 ± 2.8, respectively, p < 0.01). Similarly, LV systolic function showed significant improvement in the group of patients performing HIIT (ejection fraction: 53.1 ± 6.4 vs. 52.3 ± 5.4%, p < 0.01; GLS: −17.8 ± 3.8 vs. −15.4 ± 4.3, p < 0.01). In addition, LA strain was improved. MW efficiency was also increased in the HIIT group (91.1 ± 3.3 vs. 87.4 ± 4.1%, p < 0.01), and was closely related to peak effort measurements expressed in peak VO2 by CPET. Conclusions: In patients with recent ACS, the HIIT rehabilitation program determined reverse cardiac remodeling, with the improvement of diastolic and systolic function, assessed by standard echocardiography. In addition, cardiac deformation index as GLS, LA strain and MW efficiency improved significantly after HIIT, and were associated with functional capacity during effort.

Role of Cardiac Rehabilitation After Ventricular Assist Device Implantation.

Patients with heart failure suffered by a complex syndrome, where the filling of the ventricle or ejection of the blood is impaired. In this setting, the exercise capacity decreases for many reasons, one of them being the insufficient oxygen transfer due to reduced cardiac output and anemia. Ventricular assist device has emerged as a durable and safe therapy for patients with end-stage heart failure. The benefits of cardiac rehabilitation in ventricular assist device patients are enormous: the first aim is to progressively reduce the physical and functional impairments of these patients, so that they will be able to resume meaningful daily activities.

[Development of Multi-parameter Cardiopulmonary Exercise Test System].

In order to comprehensively evaluate the human body's functions of breathing, heart function and circulation metabolism under controlled conditions to diagnose respiratory and cardiac functions, a cardiopulmonary exercise test (CPET) system was developed. The system is divided into two parts:hardware and software. The hardware part includes measurement of six life information monitoring signals such as 12-lead ECG, respiratory mechanics, blood pressure, blood oxygen, carbon dioxide and oxygen. The software part realizes waveform display, storage and playback, et al. The experimental results show that the system is safe and reliable which provides reliable measurement parameters for evaluating human respiratory, cardiac function, circulation, metabolism and other functions. It has a good application prospect.

Validity of the modified shuttle walk test to assess cardiorespiratory fitness after exercise intervention in overweight/obese adults with primary hypertension.

The study aimed to assess whether the Modified Shuttle Walk Test (MSWT) can detect changes in cardiorespiratory fitness (CRF) in overweight/obese people with hypertension (HTN) after an exercise intervention evaluating the equation presented in the previous research by Jurio-Iriarte et al. Participants (N= 248) performed a peak cardiorespiratory exercise test (CPET) and MSWT before and after 16-weeks of different types of aerobic exercise intervention. The formula of Jurio-Iriarte et al. was used to predict peak oxygen uptake (V̇O2peak). The correlation between measured and predicted V̇O2peak was strong (r= 0.76, P< 0.001) with a standard error of estimate (SEE) of 4.9 mL·kg-1·min-1; SEE%= 17%. The intraclass correlation coefficient indicates a moderate level of association and agreement (ICC= 0.69; 95% CI 0.34-0.82; P< 0.001) between the measured and predicted V̇O2peak. When analyzing obese participants alone (N= 128), MSWT equation was more accurate compared to the whole sample (ICC= 0.76; 95% CI 0.52-0.87). The relationship between the change of measured and predicted V̇O2peak at follow-up was weak (r= 0.42, P< 0.001) with a 31% SEE, and a low level of association and agreement (ICC= 0.31; 95% CI 0.06-0.49; P< 0.001). In conclusion, although MSWT does not accurately predict CRF in people with HTN after exercise intervention and questions its validity, the new equation may have practical application to estimate V̇O2peak for obese people with HTN when CPET is not available. Abbreviations: AC: Attention Control; BM: Body Mass; BP: Blood Pressure; CI: Confidence Interval; CRF: Cardiorespiratory Fitness; CPET: Cardiopulmonary Exercise Test; HTN: Primary Hypertension; HR: Heart Rate; HV-HIIT: High-Volume and High-Intensity Interval Training; ICC: Intraclass Correlation Coefficient; LV-HIIT: Low-Volume and High-Intensity Interval Training; MICT: Moderate-intensity continuous training; MSWT: Modified Shuttle Walk Test; SD: Standard Deviation; SEE: Standard Error of Estimate; V̇O2peak: Peak Oxygen Uptake.

Wave Intensity Analysis: Sex-Specific Differences in Hemodynamic and Ventilatory Responses to Graded Exercise-Echocardiographic Measurements.

BACKGROUND: The differences in hemodynamic and ventilatory responses to graded exercise between men and women have not been well documented. Using wave intensity (WI) analysis, which is useful for analyzing ventriculo-arterial interaction, we aimed to elucidate the sex-specific differences. METHODS: We enrolled 48 healthy subjects (24 men and 24 women, age 21.3 ± 1.6 and 20.5 ± 0.9 years, n.s. [not significant]). Using ultrasonic diagnostic equipment, we measured WI, arterial stiffness parameter (ß), force-frequency relation (FFR) and other hemodynamic parameters in the carotid artery before and during graded bicycle exercise. We also analyzed expired gas volume (VE) during the exercise. The workload was increased stepwise by 20 W at 1-min intervals up to respiratory compensation (RC) point through the anaerobic threshold (AT). WI is defined as WI = (dP/dt) (dU/dt), where P is blood pressure, U is velocity, and t is time. The peak value of WI (W1) increases with left ventricular (LV) peak dP/dt, in other words, an index of cardiac contractility. The FFR was obtained as the linear regression line of W1 on heart rate. ß is defined as ß = ln (Ps/Pd)/[(Ds - Dd)/Dd], where D is the arterial diameter, and suffixes s and d indicate systolic and diastolic, respectively. RESULTS: There was no difference in the body mass index between men and women. Carbon dioxide outputs (VCO2) did not differ at rest, but those at AT and RC were greater in men. Oxygen consumptions (VO2) in men and women at rest did not differ, but those in men at AT and RC were greater. Workloads per body weight in men and women did not differ at AT, but they were greater in men at RC. Systolic pressures at rest, AT and RC were greater in men than women. Heart rates in men and women did not differ at any stage of the graded exercise. W1 did not differ at rest and AT, but it was greater in men than women at RC. The slope of the FFR during the period from rest to AT did not differ between men and women. However, the slope of the FFR during the period from AT to RC was greater in men. CONCLUSIONS: The reached values of workload/weight at RC, VCO2 at AT and RC, VO2 at AT and RC, W1 at RC, and the slope of the FFR during the period from AT to RC were greater in men than women.

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up.

Validation of an Arm Crank Ergometer Test for Use in Sedentary Adults.

The maximal oxygen uptake (V̇O2peak) test is an approved pre-operative examination tool, in a clinical setting: Both V̇O2peak and anaerobic threshold indicate a patient's physiological tolerance for major surgery and post-operative mortality, with cycle ergometry being routinely used for V̇O2peak tests in clinical settings, in many European countries. Nevertheless, the opportunities to assess populations with restricted mobility of the lower limbs are limited, as alternative methods (such as an arm-crank test protocol) to assess V̇O2peak are yet to be established. Twelve sedentary middle-aged adults (55.1 ± 5.0 years) performed two incremental protocols on an arm crank and cycle ergometer on separate occasions. During exercise, gas exchange was collected and analysed by an online breath-by-breath analysis system. Regression analysis showed that the model with dependent variable cycle ergometer V̇O2peak (CEV̇O2peak) in ml·kg-1·min-1 and independent variables arm crank V̇O2peak (ACEV̇O2peak) in ml·kg-1·min-1, lean body mass lower limbs (LBMLL) and total lean body mass (TLBM) fitted the population the best, with r2 = 0.87, adj. r2 = 0.82 and SEE = 3.14. The equation estimated with this model is: CE V̇O2peak = 11.776 + 1.418 X ACE V̇O2peak(ml·kg-1·min-) - 1.454 x TLBM + 3.967 X LLLBM. Our study suggests that arm cranking could be an alternative mode of exercise for sedentary middle-aged adults (and potentially in clinical settings) to assess the cardiorespiratory fitness of people with restricted lower-limb mobility.

Unsophisticated assessment of the cardiopulmonary function in patients with pectus excavatum using the six minute walk test.

BACKGROUND: We explored whether the maximum predicted walking distance, assessed with six-minute walk test (6MWT) and reflecting submaximal functional exercise capacity, is decreased among patients with pectus excavatum (PEX). METHODS: This study comprised a retrospective analysis of patients with PEX who underwent a 6MWT for the assessment of functional capacity. The maximum distance walked was recorded and compared to reference values established for different populations, including a young and healthy South American population. RESULTS: We included 43 patients with PEX who underwent 6MWT. The mean age was 17.8 ± 6.7 years. The mean maximum distance walked was significantly lower than the predicted distance (600.8 ± 67.6 metres vs. 729.8 ± 67.5 metres, p < 0.0001). Using the Enright reference equation including an older reference population, the mean negative difference was higher (PEX patients walked 190.4 ± 78.4 metres less than predicted, p < 0.0001). We also applied the Li et al. reference equation accounting for sex among other variables, detecting a decreased walked distance compared to the gender-adjusted predicted distance (PEX patients walked a mean 222.4 ± 87.4 metres less than predicted, p < 0.0001). Using the Ulrich et al. equation, PEX patients walked a mean 114.2 ± 85.1 metres less than predicted (p < 0.0001). Although of uncertain clinical relevance, there was a significant decrease in the mean oxygen saturation after exercise (baseline 97.4 ± 1.2%, vs. final 96.4 ± 2.1%, p = 0.006). CONCLUSIONS: In this study, we identified a significant reduction in the maximum walked distance among patients with PEX compared to the predicted distance, thus potentially emerging as an unsophisticated means to evaluate and quantify functional exercise capacity.

Effects of Sacubitril/Valsartan on Exercise Capacity in Patients with Heart Failure with Reduced Ejection Fraction and the Role of Percentage of Delayed Enhancement Measured by Cardiac Magnetic Resonance in Predicting Therapeutic Response: A Multicentre Study.

Background: This study aims to evaluate the cardiopulmonary effects of sacubitril/valsartan therapy in patients with heart failure with reduced ejection fraction (HFrEF), investigating a possible correlation with the degree of myocardial fibrosis, as assessed by cardiac magnetic resonance. Methods: A total of 134 outpatients with HFrEF were enrolled. Results: After a mean follow-up of 13.3 ± 6.6 months, an improvement in ejection fraction and a reduction in E/A ratio, inferior vena cava size and N-terminal pro-B-type natriuretic peptide levels were observed. At follow-up, we observed an increase in VO2 peak of 16% (p<0.0001) and in O2 pulse of 13% (p=0.0002) as well as an improvement in ventilatory response associated with a 7% reduction in the VE/VCO2 slope (p=0.0001). An 8% increase in the ΔVO2/Δ work ratio and an 18% increase in exercise tolerance were also observed. Multivariate logistic regression analysis showed that the main predictors of events during follow-up were VE/VCO2 slope >34 (OR 3.98; 95% CI [1.59-10.54]; p=0.0028); ventilatory oscillatory pattern (OR 4.65; 95% CI [1.55-16.13]; p=0.0052); and haemoglobin level (OR 0.35; 95% CI [0.21-0.55]; p<0.0001). In patients who had cardiac magnetic resonance, when delayed enhancement >4.6% was detected, a lower response after sacubitril/valsartan therapy was observed as expressed by improvement in ΔVO2 peak, O2 pulse, LVEF and N-terminal pro-B-type natriuretic peptide. No significant differences were observed in ΔVO2/Δ work and VE/VCO2 slope. Conclusion:Sacubitril/valsartan improves cardiopulmonary functional capacity in HFrEF patients. The presence of myocardial fibrosis on cardiac magnetic resonance is a predictor of response to therapy.

Exercise-Induced Pulmonary Hypertension Is Associated with High Cardiovascular Risk in Patients with HIV.

Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with low (n = 43) or intermediate (n = 3) probability of resting PH, we evaluated the CV risk score based on prognostic determinants of CV risk. Diagnosis of ExPH was made by cardiopulmonary exercise test (CPET) and exercise stress echocardiogram (ESE). Results: Twenty-eight % (n = 13) of the enrolled patients had ExPH at both CPET and ESE, with good agreement between the two methods (Cohen's kappa = 0.678). ExPH correlated directly with a higher CV score (p < 0.001). Patients with a higher CV score also had lower CD4+ T-cell counts (p = 0.001), a faster progression to acquired immunodeficiency syndrome (p < 0.001), a poor immunological response to antiretroviral therapy (p = 0.035), higher pulmonary vascular resistance (p = 0.003) and a higher right atrial area (p = 0.006). Conclusions: Isolated ExPH is associated with a high CV risk score in patients with HIV. Assessment of ExPH may better stratify CV risk in patients with HIV.

A patient-centered multidisciplinary cardiac rehabilitation program improves glycemic control and functional outcome in coronary artery disease after percutaneous and surgical revascularization.

BACKGROUND: Cardiac rehabilitation (CR) is strongly associated with all-cause mortality reduction in patients with coronary artery disease (CAD). The impact of CR on pathological risk factors, such as impaired glucose tolerance (IGT) and functional recovery remains under debate. The aim of the present study is to determine whether CR had a positive effect beside physical exercise improvement on pathological risk factors in IGT and diabetic patients with CAD. METHODS: One hundred and seventy-one consecutive patients participating in a 3-month CR from January 2014 to June 2015 were enrolled. The primary endpoint was defined as an improvement of peak workload and VO2-peak; glycated hemoglobin (HbA1c) reduction was considered as secondary endpoint. RESULTS: Euglycemic patients presented a significant improvement in peak workload compared to diabetic patients (from 5.75 ± 1.45 to 6.65 ± 1.84 METs vs. 4.8 ± 0.8 to 4.9 ± 1.4 METs , p = 0.018). VO2-peak improved in euglycemic patients (VO2-peak from 19.3 ± 5.3 to 22.5 ± 5.9 mL/min/kg, p = 0.003), while diabetic patients presented only a statistically significant trend (VO2-peak from 16.9 ± 4.4 to 18.0 ± 3.8 mL/min/kg, p < 0.056). Diabetic patients have benefited more in terms of blood glucose control compared to IGT patients (HbA1c from 7.7 ± 1.0 to 7.4 ± 1.1 compared to 5.6 ± 0.4 to 5.9 ± 0.5, p = 0.02, respectively). CONCLUSIONS: A multidisciplinary CR program improves physical functional capacity in CAD setting, particularly in euglycemic patients. IGT patients as well as diabetic patients may benefit from a CR program, but long-term outcome needs to be clarified in larger studies.

Can the Six-Minute Walk Test Be Used to Individualize Physical Activity Intensity in Patients with Breast Cancer?

BACKGROUND: Adapted physical activity (APA) aids breast cancer patients. It is necessary to use an adapted target heart rate (HR) when prescribing exercise intensity. METHODS: In total, 138 patients previously included in two published randomized clinical trials underwent the CPET and 6MWT before and after adjuvant therapy. Of these patients, 85 had performed APA, and 53 had received only the usual therapy. HRs were recorded during the two tests. RESULTS: Before starting chemotherapy, good agreement (intraclass correlation (ICC) 0.69; confidence interval at 95% IC0.95 (0.591-0.769); p < 0.001) and a moderate correlation were evident between the 6MWT-HR and ventilatory threshold HR of the CPET (r = 0.70; p < 0.001). Good agreement and a high positive correlation were noted only in the group who engaged in APA (ICC 0.77; IC0.95 (0.659-0.848); p < 0.001; r = 0.8; p < 0.01); moderate agreement and a moderate positive correlation were apparent in the control group (ICC 0.57; IC0.95 (0.329-0.74); p < 0.001; r = 0.6; p < 0.01). The correlations were independent of age and body mass index. CONCLUSIONS: The 6MWT-HR can be used to prescribe exercise intensity for breast cancer patients both before and after specific treatment with concomitant APA.

Cardiorespiratory Fitness Predicted by Fibrinogen and Leptin Concentrations in Children with Obesity and Risk for Diabetes: A Cross-Sectional Study and a ROC Curve Analysis.

Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health. The ability to exercise is affected by adiposity, and this mechanism involves low-grade chronic inflammation and homeostatic stress produced mainly in adipocytes, which can result in abnormal adipokine secretion. To date, the gold standard for cardiorespiratory fitness assessment is considered to be the maximum oxygen uptake (VO2max). The aim of the present study was to assess the prognostic value of hematological parameters of childhood obesity, as potential predictors of cardiorespiratory fitness (VO2max), using a sample of children and adolescents with obesity and risk for diabetes. A total of 84 clinically healthy children and adolescents were recruited, of which 21 were considered lean, 22 overweight and 41 obese, with a mean age of 12.0 ± 1.9, 11.4 ± 2.0, and 11.2 ± 2.1 years old, in each weight status category, respectively. Age and sex did not differ between groups. Hematologic testing was performed after 12 h of fasting including glucose, serum lipids, insulin, hc-CRP, adiponectin, leptin and fibrinogen levels. Cardiorespiratory capacity for exercise was assessed to determine VO2max, using a cycle ergometer. The VO2max was negatively correlated with progressive strength to the BMIz (-0.656, p ≤ 0.001), hs-CRP (r = -0.341, p ≤ 0.002), glucose (r = -0.404, p ≤ 0.001) and insulin levels (r = -0.348, p ≤ 0.001), the homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.345, p ≤ 0.002), as well as to the leptin (r = -0.639, p ≤ 0.001) and fibrinogen concentrations (r = -0.520, p ≤ 0.001). The multivariate analysis revealed that only leptin and fibrinogen concentrations could predict the VO2max adjusted for the BMIz of participants. The receiver operating characteristic (ROC) curve for the diagnostic accuracy of leptin, hs-CRP and fibrinogen concentrations for the prediction of VO2max revealed a good diagnostic ability for all parameters, with leptin being the most promising one (area under the curve (AUC): 99%). The results verify that in children with obesity, VO2max may be predicted from hematological parameters (leptin and fibrinogen), possibly bypassing more invasive methods.

Vo2peak in Adult Survivors of Hodgkin Lymphoma: Rate of Decline, Sex Differences, and Cardiovascular Events.

BACKGROUND: Adult survivors of Hodgkin lymphoma (HL) are at increased risk of cardiovascular (CV) events secondary to mediastinal radiation therapy (RT). OBJECTIVES: In this group of patients, we assessed the association between cardiopulmonary exercise testing (CPET), as determined by percent-predicted peak Vo2 (ppVo2peak), and clinical outcomes, as well as the rate of ppVo2peak decline and sex differences. METHODS: All survivors of HL who were >10 years post chest RT and who underwent ≥1 CPET were enrolled from a single center. Traditional CV and treatment risk factors, along with CV events, were ascertained. RESULTS: A total of 64 patients (67% female; median age 51 years [range 26 to 70 years]) with a median follow-up time after RT of 23 years (range 11 to 41 years), and 141 CPET studies, were included. Median initial ppVo2peak was 91% (range 58% to 138%). ppVo2peak in survivors declined by 7.5 percentage points every 10-year period after RT, as compared with age- and sex-based norms (P = 0.001), even after adjusting for hypertension and history of anthracycline. Both male and female patients had a similar rate of ppVo2peak decline. However, women had a lower ppVo2peak at all times, and they developed abnormal ppVo2peak (≤85%) on average earlier than men (24.1 years vs 47.0 years after RT). Patients with abnormal ppVo2peak vs normal ppVo2peak (>85%), had an increased risk of CV events (59% vs 16%). Abnormal ppVo2peak was independently associated with the risk of CV events (adjusted HR: 6.37; 95% CI: 2.06-19.80; P = 0.001). CONCLUSIONS: Percent-predicted Vo2peak in long-term survivors of HL who were treated with chest RT progressively declined as compared with population- and sex-based norms. Importantly, women developed abnormal ppVo2peak more than 2 decades earlier than male survivors. Abnormal ppVo2peak was associated with an increased risk of CV events in this group of patients.

Improvement of functional capacity in sacubitril-valsartan treated patients assessed by cardiopulmonary exercise test.

Neprilisin and angiotensin receptor inhibition (Sacubitril/Valsartan, i.e. ARNI) is recommended in heart failure guidelines for patients in NYHA class II-III with reduced left ventricular ejection fraction (LVEF). ARNI increase survival and quality of life; due to their hemodynamic effects, ARNI could also affect exercise tolerance. We studied the effects of ARNI on cardiopulmonary test (CPET) after six months of treatment in 35 patients [67 ± 11 years; LVEF 31 ± 6%; NT-proBNP 1822 ± 1651 pg/ml; ICD/CRT since at least 6 months in 26/35], treated with increasing doses of Sacubitril/Valsartan up to 318 ± 36 mg/die. In addition, levels of NT-proBNP, renal function, electrolytes, and echocardiocolorDoppler were assessed in the same time periods. No variations of renal function and/or potassium levels were observed; NT-proBNP decreased. Most CPET variables were improved by ARNI (p < .05): peak VO2 and O2 pulse increased (from 15.8 ± 3.4 to 17.0 ± 4.0 ml/kg/min and from 11.5 ± 2.5 to 12.6 ± 2.4 ml/beat, respectively), while VEVCO2 slope decreased from 35.2 ± 11.2 to 33.1 ± 12.3. A significant relationship (p < .05) was observed between the amount of increase in LVEF and that of O2 pulse in all patients, and between the amount of decrease in PAPs and that of VEVCO2 slope in patients showing pulmonary hypertension in baseline. In a subgroup of 22 patients who already completed A 1 year follow-up, overall CPET improvement was maintained. In conclusion, already in the short term ARNI favourably affect cardiopulmonary response to exercise in heart failure patients; such a change seems to be preserved on a longer period.

Early Effects of Sacubitril/Valsartan on Exercise Tolerance in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF. METHODS: We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy. RESULTS: At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3⁻14.9 months) systolic blood pressure decreased from 117 ± 14 to 101 ± 12 mmHg (p < 0.0001), left ventricular ejection fraction (LVEF) increased from 27 ± 6 to 29.7 ± 7% (p < 0.0001), peak oxygen consumption (VO2) improved from 14.6 ± 3.3 (% of predicted = 53.8 ± 14.1) to 17.2 ± 4.7 mL/kg/min (% of predicted = 64.7 ± 17.8) (p < 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO2 Slope) decreased from 34.1 ± 6.3 to 31.7 ± 6.1 (p = 0.006), VO2 at anaerobic threshold increased from 11.3 ± 2.6 to 12.6 ± 3.5 mL/kg/min (p = 0.007), oxygen pulse increased from 11.5 ± 3.0 to 13.4 ± 4.3 mL/kg/min (p < 0.0001), and ∆VO2/∆Work increased from 9.2 ± 1.5 to 10.1 ± 1.8 mL/min/watt (p = 0.0002). CONCLUSION: Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO2, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.

Thigh Ischemia-Reperfusion Model Does Not Accelerate Pulmonary VO 2 Kinetics at High Intensity Cycling Exercise.

Background: We aimed to investigate the effect of a priming ischemia-reperfusion (IR) model on the kinetics of pulmonary oxygen uptake (VO2) and cardiopulmonary parameters after high-intensity exercise. Our primary outcome was the overall VO2 kinetics and secondary outcomes were heart rate (HR) and O2 pulse kinetics. We hypothesized that the IR model would accelerate VO2 and cardiopulmonary kinetics during the exercise. Methods: 10 recreationally active men (25.7 ± 4.7 years; 79.3 ± 10.8 kg; 177 ± 5 cm; 44.5 ± 6.2 mL kg-1 min-1) performed a maximal incremental ramp test and four constant load sessions at the midpoint between ventilatory threshold and VO2 max on separate days: two without IR (CON) and two with IR (IR). The IR model consisted of a thigh bi-lateral occlusion for 15 min at a pressure of 250 mmHg, followed by 3 min off, before high-intensity exercise bouts. Results: There were no significant differences for any VO2 kinetics parameters (VO2 base 1.08 ± 0.08 vs. 1.12 ± 0.06 L min-1; P = 0.30; τ = 50.1 ± 7.0 vs. 47.9 ± 6.4 s; P = 0.47), as well as for HR (MRT180s 67.3 ± 6.0 vs. 71.3 ± 6.1 s; P = 0.54) and O2 pulse kinetics (MRT180s 40.9 ± 3.9 vs. 48.2 ± 5.6 s; P = 0.31) between IR and CON conditions, respectively. Conclusion: We concluded that the priming IR model used in this study had no influence on VO2, HR, and O2 pulse kinetics during high-intensity cycling exercise.

Dissecting functional impairment in hypertrophic cardiomyopathy by dynamic assessment of diastolic reserve and outflow obstruction: A combined cardiopulmonary-echocardiographic study.

BACKGROUND: Exercise limitation in hypertrophic cardiomyopathy (HCM) patients is often attributed to left ventricular outflow tract (LVOT) obstruction and diastolic impairment. However, these features assessed at rest fail to predict performance. To evaluate their variations and interplay during effort in HCM, we performed echocardiographic assessment of diastolic function and outflow obstruction during cardiopulmonary test (CPX). METHODS: We included 197 HCM patients (mean age 45±15years, 129 males), undergoing CPX. Diastolic dysfunction (DD) grade was measured at baseline and at peak exercise. Oxygen consumption (VO2 max) values <75% of maximum predicted were considered abnormal. RESULTS: One hundred-seven patients (54%) had DD grade II-III at rest (Rest DD), 40 (20%) showed preserved diastolic function (grade 0/I) both at rest and on effort (No DD). The remaining 50 patients (25%) had a grade 0/I pattern at rest but exhibited impaired diastolic reserve on exercise (Latent DD). Latent DD was associated with higher prevalence of patients with VO2<75% in both the non-obstructive and the latent-obstructive group: at multivariate regression analysis, left atrium volume index, LV obstruction at rest and rest or latent DD were significantly associated with lower peak VO2. Excluding rest-obstructive patients from the analysis, rest- or latent DD were the only determinants of exercise impairment (latent-obstructive, OR 8.9; 95% CI 1.5-18.8; p=0.012; non-obstructive, OR 2.2; 95% CI 1.0-5.8; p=0.03). CONCLUSION: Latent DD is a major determinant of exercise intolerance in HCM. Comprehensive assessment of outflow obstruction and diastolic reserve during cardiopulmonary test represents an important adjunct to clinical management.