Being fit in the COVID-19 era and future epidemics prevention: Importance of cardiopulmonary exercise test in fitness evaluation.

Endurance and resistance physical activity have been shown to stimulate the production of immunoglobulins and boost the levels of anti-inflammatory cytokines, natural killer cells, and neutrophils in the bloodstream, thereby strengthening the ability of the innate immune system to protect against diseases and infections. Coronavirus disease 19 (COVID-19) greatly impacted people's cardiorespiratory fitness (CRF) and health worldwide. Cardiopulmonary exercise testing (CPET) remains valuable in assessing physical condition, predicting illness severity, and guiding interventions and treatments. In this narrative review, we summarize the connections and impact of COVID-19 on CRF levels and its implications on the disease's progression, prognosis, and mortality. We also emphasize the significant contribution of CPET in both clinical evaluations of recovering COVID-19 patients and scientific investigations focused on comprehending the enduring health consequences of SARS-CoV-2 infection.

Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum.

The goal of this study is to quantify the assumptions associated with the Wasserman-Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2 ) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent-predicted VO2 (ppVO2 ) values for both equations and compared them using the Bland-Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age-adjusted VO2 ratios (pVO2 /pre-exercise VO2 ) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2 , pVO2 26.8 mlO2 /kg/min). The Bland-Altman plot revealed an average relative difference of -1.7% (95% CI: -2.1 to -1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.

Improving Reporting of Exercise Capacity Across Age Ranges Using Novel Workload Reference Equations.

Exercise capacity (EC) is an important predictor of survival in the general population and in subjects with cardiopulmonary disease. Despite its relevance, considering the percent-predicted workload (%pWL) given by current equations may overestimate EC in older adults. Therefore, to improve the reporting of EC in clinical practice, our main objective was to develop workload reference equations (pWL) that better reflect the relation between workload and age. Using the Fitness Registry and the Importance of Exercise National Database (FRIEND), we analyzed a reference group of 6,966 apparently healthy participants and 1,060 participants with heart failure who underwent graded treadmill cardiopulmonary exercise testing. For the first group, the mean age was 44 years (18 to 79); 56.5% of participants were males and 15.4% had obesity. Peak oxygen consumption was 11.6 ± 3.0 METs in males and 8.5 ± 2.4 METs in females. After partition analysis, we first developed sex-specific pWL equations to allow comparisons to a healthy weight reference. For males, pWL (METs) = 14.1-0.9×10-3×age2 and 11.5-0.87×10-3×age2 for females. We used those equations as denominators of %pWL, and based on their distribution, we determined thresholds for EC classification, with average EC defined by the range corresponding to 85% to 115%pWL. Compared with %pWL using current equations, the new equations yielded better-calibrated %pWL across different age ranges. We also derived body mass index-adjusted pWL equations that better assessed EC in subjects with heart failure. In conclusion, the novel pWL equations have the potential to impact the report of EC in practice.

Assessing the Assisted Six-Minute Cycling Test as a Measure of Endurance in Non-Ambulatory Patients with Spinal Muscular Atrophy (SMA).

Assessing endurance in non-ambulatory individuals with Spinal Muscular Atrophy (SMA) has been challenging due to limited evaluation tools. The Assisted 6-Minute Cycling Test (A6MCT) is an upper limb ergometer assessment used in other neurologic disorders to measure endurance. To study the performance of the A6MCT in the non-ambulatory SMA population, prospective data was collected on 38 individuals with SMA (13 sitters; 25 non-sitters), aged 5 to 74 years (mean = 30.3; SD = 14.1). The clinical measures used were A6MCT, Revised Upper Limb Module (RULM), Adapted Test of Neuromuscular Disorders (ATEND), and Egen Klassifikation Scale 2 (EK2). Perceived fatigue was assessed using the Fatigue Severity Scale (FSS), and effort was assessed using the Rate of Perceived Exertion (RPE). Data were analyzed for: (1) Feasibility, (2) Clinical discrimination, and (3) Associations between A6MCT with clinical characteristics and outcomes. Results showed the A6MCT was feasible for 95% of the tested subjects, discriminated between functional groups (p = 0.0086), and was significantly associated with results obtained from RULM, ATEND, EK2, and Brooke (p < 0.0001; p = 0.029; p < 0.001; p = 0.005). These findings indicate the A6MCT's potential to evaluate muscular endurance in non-ambulatory SMA individuals, complementing clinician-rated assessments. Nevertheless, further validation with a larger dataset is needed for broader application.

Personalized digital behaviour interventions increase short-term physical activity: a randomized control crossover trial substudy of the MyHeart Counts Cardiovascular Health Study.

Aims: Physical activity is associated with decreased incidence of the chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity. Methods and results: We offered enrolment to community-living iPhone-using adults aged ≥18 years in the USA, UK, and Hong Kong who downloaded the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomized to four 7-day interventions. Interventions consisted of: (i) daily personalized e-coaching based on the individual's baseline activity patterns, (ii) daily prompts to complete 10 000 steps, (iii) hourly prompts to stand following inactivity, and (iv) daily instructions to read guidelines from the American Heart Association (AHA) website. After completion of one 7-day intervention, participants subsequently randomized to the next intervention of the crossover trial. The trial was completed in a free-living setting, where neither the participants nor investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis (modified in that participants had to complete 7 days of baseline monitoring and at least 1 day of an intervention to be included in analyses). This trial is registered with ClinicalTrials.gov, NCT03090321. Conclusion: Between 1 January 2017 and 1 April 2022, 4500 participants consented to enrol in the trial (a subset of the approximately 50 000 participants in the larger MyHeart Counts study), of whom 2458 completed 7 days of baseline monitoring (mean daily steps 4232 ± 73) and at least 1 day of one of the four interventions. Personalized e-coaching prompts, tailored to an individual based on their baseline activity, increased step count significantly (+402 ± 71 steps from baseline, P = 7.1⨯10-8). Hourly stand prompts (+292 steps from baseline, P = 0.00029) and a daily prompt to read AHA guidelines (+215 steps from baseline, P = 0.021) were significantly associated with increased mean daily step count, while a daily reminder to complete 10 000 steps was not (+170 steps from baseline, P = 0.11). Digital studies have a significant advantage over traditional clinical trials in that they can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we present a novel finding that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized. Further studies are needed to determine the effects of digital interventions on long-term outcomes.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise.

BACKGROUND: Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. METHODS: Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. RESULTS: Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min-1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. CONCLUSIONS: Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise

Abstract Background Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. Methods Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. Results Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min−1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. Conclusions Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

Peak O2 -pulse predicts exercise training-induced changes in peak V̇O2 in heart failure with preserved ejection fraction.

AIMS: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O2 ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O2 -pulse (V̇O2  × HR-1 , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O2 , is inversely associated with the change in peak V̇O2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. METHODS AND RESULTS: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O2 (%) was analysed as a function of baseline peak V̇O2 and its determinants (absolute peak V̇O2 , peak O2 -pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O2 through changes in peak O2 -pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O2 -pulse explained approximately 72% of the difference in changes in peak V̇O2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O2 -pulse on change in peak V̇O2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O2 -pulse was associated with a decreased mean change in peak V̇O2 of -1.45% (95% CI, -2.30 to -0.60, P = 0.001) compared with a mean change of -0.08% (95% CI, -1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O2 (P > 0.05). Change in V̇O2 at VT1 was not associated with any of the investigated factors (P > 0.05). CONCLUSIONS: In patients with HFpEF, the easily measurable peak O2 -pulse seems to be a good indicator of the potential for improving peak V̇O2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O2 -pulse, patients with high O2 -pulse may need to use additional therapies to significantly increase peak V̇O2 .

Post pandemic research priorities: A consensus statement from the HL-PIVOT.

We have been amid unhealthy living and related chronic disease pandemics for several decades. These longstanding crises have troublingly synergized with the coronavirus disease 2019 (COVID-19) pandemic. The need to establish research priorities in response to COVID-19 can be used to address broad health and wellbeing, social and economic impacts for the future is emerging. Accordingly, this paper sets out a series of research priorities that could inform interdisciplinary collaboration between clinical sciences, public health, business, technology, economics, healthcare providers, and the exercise science/sports medicine communities, among others. A five-step methodology was used to generate and evaluate the research priorities with a focus on broad health and well-being impacts. The methodology was deployed by an international and interdisciplinary team from the Healthy Living for Pandemic Event Protection (HL- PIVOT) network. This team were all engaged in responding to the Pandemic either on the 'front-line' and/or in leadership positions ensuring the currency and authenticity of the process. Eight research priorities were identified clustered into two groups: i) Societal & Environmental, and ii) Clinical. Our eight research priorities are presented with insight from previously published research priorities from other groups.

Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing.

Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.

Findings From Cardiovascular Evaluation of National Collegiate Athletic Association Division I Collegiate Student-Athletes After Asymptomatic or Mildly Symptomatic SARS-CoV-2 Infection.

OBJECTIVE: The risk of myocardial damage after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been controversial. The purpose of this study is to report the incidence of abnormal cardiovascular findings in National Collegiate Athletic Association (NCAA) Division I student-athletes with a history of SARS-CoV-2 infection. DESIGN: This is a case series of student-athletes with SARS-CoV-2 infection and their subsequent cardiac work-up, including troponin level, electrocardiogram, and echocardiogram. Additional testing was ordered as clinically indicated. SETTING: This study was conducted at a single NCAA Division I institution. PARTICIPANTS: Student-athletes were included if they tested positive for SARS-CoV-2 by PCR or antibody testing [immunoglobulin G (IgG)] from April 15, 2020 to October 31, 2020. INTERVENTION: Cardiac testing was conducted as part of postinfection screening. MAIN OUTCOME MEASURES: This study was designed to quantify abnormal cardiovascular screening results and cardiac diagnoses after SARS-CoV-2 infection in Division I collegiate athletes. RESULTS: Fifty-five student-athletes tested positive for SARS-CoV-2. Of these, 14 (26%) had a positive IgG and 41 (74%) had a positive PCR test. Eight abnormal cardiovascular screening evaluations necessitated further testing including cardiac magnetic resonance imaging (cMRI). Two athletes received new cardiac diagnoses, one probable early cardiomyopathy and one pericarditis, whereas the remaining 6 had normal cMRIs. CONCLUSIONS: These data support recent publications which recommend the de-escalation of cardiovascular testing such as cardiac MRI or echocardiogram for athletes who have recovered from asymptomatic or mildly symptomatic SARS-CoV-2 infection. Continued follow-up of these athletes for sequelae of SARS-CoV-2 is critical.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology.

Background: Exercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO2) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM). Methods: The Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program. Patients were stratified for HFrEF etiology (ICM versus NICM) and randomly assigned (1:1:1) to supervised exercise thrice weekly: a) moderate continuous training (MCT) at 60-70 % of peak heart rate (HR), b) high intensity interval training (HIIIT) at 90-95 % peak HR, or c) recommendation of regular exercise (RRE) according to guidelines. LVEDD, LVEF and peak VO2 were assessed at baseline, after 12 and 52 weeks. Results: 215 patients completed the intervention. ICM (59 %; n = 126) compared to NICM patients (41 %; n = 89) had significantly lower peak VO2 values at baseline and after 12 weeks (difference in peak VO2 2.2 mL/(kg*min); p < 0.0005) without differences between time points (p = 0.11) or training groups (p = 0.15). Etiology did not influence changes of LVEDD or LVEF (p = 0.30; p = 0.12), even when adjusting for sex, age and smoking status (p = 0.54; p = 0.12). Similar findings were observed after 52 weeks. Conclusions: Etiology of HFrEF did not influence the effects of moderate or high intensity exercise on cardiac dimensions, systolic function or exercise capacity. Clinical Trial Registration­URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Rethinking Rehabilitation: A REVIEW OF PATIENT POPULATIONS WHO CAN BENEFIT FROM CARDIAC REHABILITATION.

Although cardiac rehabilitation (CR) is safe and highly effective for individuals with various cardiovascular health conditions, to date there are only seven diagnoses or procedures identified by the Centers for Medicare & Medicaid Services that qualify for referral. When considering the growing number of individuals with cardiovascular disease (CVD), or other health conditions that increase the risk for CVD, it is important to determine the extent for which CR could benefit these populations. Furthermore, there are some patients who may currently be eligible for CR (spontaneous coronary artery dissection, left ventricular assistant device) but make up a relatively small proportion of the populations that are regularly attending and participating. Thus, these patient populations and special considerations for exercise might be less familiar to professionals who are supervising their programs. The purpose of this review is to summarize the current literature surrounding exercise testing and programming among four specific patient populations that either do not currently qualify for (chronic and end-stage renal disease, breast cancer survivor) or who are eligible but less commonly seen in CR (sudden coronary artery dissection, left ventricular assist device). While current evidence suggests that individuals with these health conditions can safely participate in and may benefit from supervised exercise programming, there is an immediate need for high-quality, multisite clinical trials to develop more specific exercise recommendations and support the inclusion of these populations in future CR programs.

Comparison of the FRIEND and Wasserman-Hansen Equations in Predicting Outcomes in Heart Failure.

Background Percentage of age-predicted peak oxygen uptake (VO2) achieved (ppVO2) has been widely used to stratify risk in patients with heart failure. However, there are limitations to traditional normal standards. We compared the recently derived FRIEND (Fitness Registry and the Importance of Exercise: A National Data Base) equation to the widely used Wasserman-Hansen (WH) ppVO2 equation to predict outcomes in patients with heart failure. Methods and Results A subgroup of 4055 heart failure patients from the FRIEND registry (mean age 53±15 years) was followed for a mean of 28±16 months. The FRIEND and WH equations along with measured peak VO2 expressed in mL/kg-1 per min-1 were compared for mortality and composite cardiovascular events. ppVO2 was higher for the FRIEND versus the WH equation (66±30% versus 58±25%; P<0.001). The areas under the receiver operating characteristic curves were slightly but significantly higher for the FRIEND equation for mortality (0.74 versus 0.72; P=0.03) and cardiac events (0.70 versus 0.68; P=0.008). Area under the receiver operating characteristic curve for measured peak VO2 was 0.70 (P<0.001) for mortality and 0.73 (P<0.001) for cardiovascular events. For each 1-SD higher ppVO2 for the FRIEND equation, mortality was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.69-0.97; P<0.02); for each 1-SD higher ppVO2 for the WH equation, the mortality was reduced by 17% (hazard ratio, 0.83; 95% CI, 0.71-0.97; P=0.02). The corresponding reductions in risk per 1 SD for cardiovascular events for the FRIEND and WH equations were 23 and 21%, respectively (both P<0.001). Conclusions Peak VO2 expressed as percentage of an age-predicted standard strongly predicts mortality and major cardiovascular events in patients with heart failure. The FRIEND registry equation exhibited test characteristics slightly superior to the commonly used WH equation.

Cardiopulmonary Exercise Testing With Echocardiography to Assess Recovery in Patients With Ventricular Assist Devices.

The left ventricular assist device (LVAD) is an established treatment for select patients with end-stage heart failure. Some patients recovered and are considered for explantation. Assessing recovery involves exercise testing and echo ramping on full and minimal LVAD support. Combined cardiopulmonary exercise testing with simultaneous echo ramping (CPET-R) has not been well studied. Patients were included if they had CPET within the previous 6 months, were clinically stable, and had an INR >2.0 on the day of examination. Patients had CPET-R on two occasions within 14 days: (a) with LVAD at therapeutic speed and (b) with LVAD at the lowest speed possible. Six patients were between 29 and 75 years (two female). One patient did not complete a turn-down test due to evidence of ischemia on initial CPET-R subsequently confirmed as a significant coronary artery stenosis on angiography. There were no significant differences in CPET or echo metrics between LVAD speeds. Two patients were explanted due to presumed LV recovery and remained event free for 30 and 47 months, respectively. Serial CPET-R seems safe and feasible for the evaluation of LV and global function and may result in improved clinical decision making for LVAD explantation.

Peripheral Oxygen Extraction and Exercise Limitation in Asymptomatic Patients with Diabetes Mellitus.

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO2) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO2). Peripheral extraction was calculated as the ratio of VO2 to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e', and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO2(<80%) and 18 (18%) presented abnormal VE/VCO2slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e' (beta = -0.24, p = 0.004) was associated with lower peak VO2 along with age, sex and body mass index (R2 = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e', relative wall thickness and peak VO2 in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO2in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM.

Current Activities Centered on Healthy Living and Recommendations for the Future: A Position Statement from the HL-PIVOT Network.

We continue to increase our cognizance and recognition of the importance of healthy living (HL) behaviors and HL medicine (HLM) to prevent and treat chronic disease. The continually unfolding events precipitated by the coronavirus disease 2019 (COVID-19) pandemic have further highlighted the importance of HL behaviors, as indicated by the characteristics of those who have been hospitalized and died from this viral infection. There has already been recognition that leading a healthy lifestyle, prior to the COVID-19 pandemic, may have a substantial protective effect in those who become infected with the virus. Now more than ever, HL behaviors and HLM are essential and must be promoted with a renewed vigor across the globe. In response to the rapidly evolving world since the beginning of the COVID-19 pandemic, and the clear need to change lifestyle behaviors to promote human resilience and quality of life, the HL for Pandemic Event Protection (HL-PIVOT) network was established. The 4 major areas of focus for the network are: (1) knowledge discovery and dissemination; (2) education; (3) policy; (4) implementation. This HL-PIVOT network position statement provides a current synopsis of the major focus areas of the network, including leading research in the field of HL behaviors and HLM, examples of best practices in education, policy, and implementation, and recommendations for the future.

Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Importance: Endurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing modes of exercise have different effects. Objective: To determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF. Design, Setting, and Participants: Randomized clinical trial at 5 sites (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway) from July 2014 to September 2018. From 532 screened patients, 180 sedentary patients with chronic, stable HFpEF were enrolled. Outcomes were analyzed by core laboratories blinded to treatment groups; however, the patients and staff conducting the evaluations were not blinded. Interventions: Patients were randomly assigned (1:1:1; n = 60 per group) to high-intensity interval training (3 × 38 minutes/week), moderate continuous training (5 × 40 minutes/week), or guideline control (1-time advice on physical activity according to guidelines) for 12 months (3 months in clinic followed by 9 months telemedically supervised home-based exercise). Main Outcomes and Measures: Primary end point was change in peak V̇o2 after 3 months, with the minimal clinically important difference set at 2.5 mL/kg/min. Secondary end points included changes in metrics of cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months. Results: Among 180 patients who were randomized (mean age, 70 years; 120 women [67%]), 166 (92%) and 154 (86%) completed evaluation at 3 and 12 months, respectively. Change in peak V̇o2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs -0.6 mL/kg/min (difference, 1.5 [95% CI, 0.4 to 2.7]); for moderate continuous training vs guideline control, 1.6 vs -0.6 mL/kg/min (difference, 2.0 [95% CI, 0.9 to 3.1]); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, -0.4 [95% CI, -1.4 to 0.6]). No comparisons were statistically significant after 12 months. There were no significant changes in diastolic function or natriuretic peptides. Acute coronary syndrome was recorded in 4 high-intensity interval training patients (7%), 3 moderate continuous training patients (5%), and 5 guideline control patients (8%). Conclusions and Relevance: Among patients with HFpEF, there was no statistically significant difference in change in peak V̇o2 at 3 months between those assigned to high-intensity interval vs moderate continuous training, and neither group met the prespecified minimal clinically important difference compared with the guideline control. These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT02078947.