Dyspnea and exercise intolerance are commonly reported post-acute sequelae of SARS-CoV-2 infection (PASC), but routine diagnostic testing is often normal. Cardiopulmonary exercise testing (CPET) ...offers comprehensive assessment of dyspnea to characterize pulmonary PASC.
We performed a retrospective cohort study of CPET performed on patients reporting dyspnea and/or exercise intolerance following confirmed Covid-19 between August 1, 2020 and March 1, 2021, and compared them to age- and sex-matched patients with unexplained dyspnea referred for CPET at the same center in the pre-Covid-19 era.
Compared to matched unexplained dyspnea comparators, PASC patients shared similar medical comorbidities and subjective dyspnea at referral (mMRC score 1.6 ± 0.9 vs. 1.4 ± 0.9, P = 0.5). Fifteen (83.3%) PASC patients underwent high resolution computed tomography of the chest, of which half (46.7%) were normal, and 17 (94.4%) patients had pulmonary function testing, of which the majority (76.5%) were normal. All patients underwent CPET, and 12 (67%) had normal findings. Compared to matched comparators, PASC patients had similar peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, and ventilatory efficiency measured by the minute ventilation to carbon dioxide production (VE/VCO2) slope.
Despite prominent dyspnea, physiological abnormalities on CPET were mild across a range of initial Covid-19 severity and similar to matched comparators referred for dyspnea without antecedent SARS-CoV-2.
The project was supported by the NHLBI (R01HL131029, R01HL151841, U10HL110337, T32HL116275) and a KL2 award (5KL2TR002542–02) from Harvard Catalyst.
Abstract only Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disorder in which abnormalities in both cardiac output (CO) and peripheral oxygen extraction (CavO 2 ...) contribute to impaired oxygen uptake (VO 2 ). We investigated the predominant limitation to VO 2 , according to distinct HFpEF criteria, by examining the CO vs. VO 2 relationship during incremental exercise. Methods: Participants underwent Cardiopulmonary Exercise Testing (CPET) with invasive hemodynamic assessment and were diagnosed with HFpEF based on characteristic symptoms and NTproBNP ≥125pg/mL, Supine PCWP ≥15mmHg, PCWP/CO ≥2mmHg/L/min or Peak PCWP ≥25mmHg. Calculated direct Fick CO versus VO 2 slope and peak exercise data were stratified by the expected relationship of CO(L/min) = 5хVO 2 (L/min) +5. The Mann Whitney U Test and t-test characterized those limited by cardiac output (Slope <5L/min) vs. peripheral extraction (Slope >5L/min). Results: In 425 dyspneic individuals meeting biomarker and/or hemodynamic criteria for HFpEF, 36% had predominantly peripheral limitation (Measured Peak CO > Expected). Among those with NTpro-BNP ≥125pg/mL or resting PCWP ≥15mmHg, or both (N=220) , 31% were peripherally limited. 41% of those with a PCWP/CO ≥2mmHg/mL/min or Peak PCWP ≥25mmHg, or both (N=205) , were peripherally limited. Among all peripherally limited patients (N=151), the percentage of females, NTpro-BNP levels, Hb levels, rest and peak Ca-vO 2 , and rest and peak PVR were significantly lower compared to the cardiac limited group (Table, N=274), while resting PCWP, LVEF and HR were similar (Table). Conclusion: Despite meeting concurrent biomarker and/or hemodynamic criteria for HFpEF, peripheral-predominant limitation to exercise capacity is common which merits consideration when deploying interventions to augment exercise capacity in HFpEF.
Abstract only Background: A high metabolic cost of initiating exercise, defined by workload equivalents of unloaded cycle ergometry exercise, has been described in obese patients with HFpEF. ...Implications of high BMI and exaggerated metabolic cost of exercise initiation on responses to incremental ramp exercise have not been defined. We hypothesized that exaggerated metabolic cost of exercise initiation would result in delayed metabolic response to incremental ramp exercise. Methods: Patients underwent invasive cardiopulmonary exercise testing (CPET) on a cycle ergometer, including rest, unloaded exercise, and maximum incremental ramp exercise. Mean response time (MRT) was defined as 67% of the time to reach steady state VO 2 during unloaded exercise. On-ramp VO 2 kinetics were defined by the amount of time that it took for VO 2 to permanently increase by 5% (t 5% ), 10% (t 10% ), and 15% (t 15% ) above steady state after initiation of incremental ramp exercise. These values were adjusted for ramp and related to demographic and CPET measures by multivariate linear regression. Results: 200 patients referred for evaluation of exertional dyspnea and suspected HFpEF (age 55 ± 16 years, 45% female, BMI of 30 ± 6 kg/m 2 , 52% HTN, 17% DM) demonstrated variability in their on-ramp VO 2 uptake kinetics after reaching steady state during unloaded exercise. Delayed VO 2 kinetic responsiveness to incremental ramp exercise, as measured by t 5% , t 10% , and t 15%, was not related to age but was directly related to BMI, internal work, and prolonged MRT for VO 2 upon exercise initiation. Conclusion: In this initial description of VO 2 uptake kinetic patterns during the transition from unloaded to incremental ramp exercise, increased BMI, slow exercise onset VO 2 kinetics, and heightened metabolic cost of exercise initiation are all related to delayed VO 2 on-ramp kinetics. Delayed on-ramp O 2 kinetics merit further evaluation in relation to functional limitations in dyspneic patients referred for suspicion of HFpEF.
IntroductionDuring maximum incremental exercise expiratory flow rates increase > 10-fold and minute ventilation can exceed 100L/min, raising concern for possible spread of COVID-19 in asymptomatic ...patients undergoing exercise testing. Moreover, use of surgical or N95 masks that limit airflow are recognized to limit the ability to perform maximum exercise.HypothesisUse of an in-line filter during cardiopulmonary exercise testing is feasible and will not adversely impact measurements of exercise capacity.MethodsWe conducted a proof-of-principle study in which a commercially available electrostat filter (Figure 1A), which has >99.9% viral efficiency without affecting spirometry measurements during pulmonary function testing, was placed in-line, upstream of the flow meter and gas analyzer sample line for use during cardiopulmonary exercise testing. A single healthy subject completed incremental exercise with a 3 min period of unloaded exercise followed by 4-min stages of exercise at 50, 100, 150, and 200W with and without the filter in place on the same day. Mechanical dead space was 53 ml with the filter and 45 ml without.ResultsIn comparison to no internal filter, use of an in-line filter resulted in VO2 measurements of 99%, 97%, 98%, and 97% during 50W, 100W, 150W, and 200W, respectively (Figure 1A). VO2/work slope measurements and measurements of minute ventilation were also highly consistent throughout exercise with and without use of an in-line filter (Figure 1B).ConclusionsExercise testing is an integral part of cardiovascular care delivery. Our findings require further validation but suggest that an in-line filtration system can be utilized in an effort to reduce droplet and viral dissemination without impacting measures of cardiopulmonary performance.
Exercise testing plays an important role in evaluating heart failure prognosis and selecting patients for advanced therapeutic interventions. However, concern for severe acute respiratory syndrome ...novel coronavirus-2 transmission during exercise testing has markedly curtailed performance of exercise testing during the novel coronavirus disease-2019 pandemic.
To examine the feasibility to conducting exercise testing with an in-line filter, 2 healthy volunteer subjects each completed 2 incremental exercise tests, one with discrete stages of increasing resistance and one with a continuous ramp. Each subject performed 1 test with an electrostatic filter in-line with the system measuring gas exchange and air flow, and 1 test without the filter in place. Oxygen uptake and minute ventilation were highly consistent when evaluated with and without use of an electrostatic filter with a >99.9% viral efficiency.
Deployment of a commercially available in-line electrostatic viral filter during cardiopulmonary exercise testing is feasible and provides consistent data compared with testing without a filter.
IntroductionExercise intolerance is common in cardiovascular disease and is a cardinal manifestation of heart failure with preserved ejection fraction (HFpEF). Decreased exercise capacity is often ...attributed to cardiac limitations, though HFpEF is increasingly recognized to be both a metabolic and a cardiovascular disorder.HypothesisPatients with HFpEF will have exaggerated metabolic cost of exercise initiation with associated high expenditure of hemodynamic reserve capacity.MethodsWe quantified the workload-equivalent cost of initiating exercise using cardiopulmonary exercise testing in patients with HFpEF (N=184, age 62±13, 47% women, peak VO2 13.8±3.3 ml/kg/min). Individualized VO2-work rate relationships during loaded exercise were used to derive the work-equivalents required to move extremities with zero external resistance (0 watts)—termed “internal work” (IW). Standard linear regression techniques were used for comparisons.ResultsIn individuals with HFpEF, the internal work (42±28 W) was often a large portion of the total workload achieved. BMI accounted for the greatest variance in IW (23%), suggesting a metabolic basis for IW. Resting measures of myocardial function and biventricular filling pressures did not measurably contribute to explanatory variance in IW, suggesting a non-cardiac origin. Individuals with HFpEF in the fourth quartile of IW (76±28W) had a dramatic hemodynamic response to exercise in pulmonary capillary wedge and mean pulmonary arterial pressures. Changes in hemodynamic measurements were more modest between quartiles of IW in the submaximal ramp period following unloaded exercise.ConclusionsInternal work is a new measure that captures the metabolic cost of initiating movement. Internal work is associated with limitations in achievable external workload as well as steep early increases in cardiac filling pressures in HFpEF. Further investigation into the pathophysiology of elevated IW is needed.
This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to ...outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF).
In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood.
We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population.
In HFpEF, only age (standardized beta = 0.593; P < 0.001), exercise stroke volume (standardized beta = 0.349; P < 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004).
In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome.
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Heart failure with preserved ejection fraction (HFpEF) is a joint metabolic and cardiovascular disorder with significant noncardiac contributions.
To define and quantify the metabolic cost of ...initiating exercise in individuals with and without HFpEF and its functional consequences.
This prospective cohort study included individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS). Analysis began April 2016 and ended November 2020.
Internal work (IW), a measure of work equivalents required to initiate movement.
Using breath-by-breath oxygen uptake (V̇o2) measurements and V̇o2-work rate associations, cost of initiating exercise (IW) in patients with HFpEF (MGH-ExS) and in community-dwelling individuals (FHS) was quantified. Linear regression was used to estimate associations between IW and clinical/hemodynamic measures.
Of 3231 patients, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. In the MGH-ExS cohort, 86 (47%) were women, the median (interquartile range) age was 63 (53-72) years, and the median (interquartile range) peak V̇o2 level was 13.33 (11.77-15.62) mL/kg/min. In the FHS cohort, 1620 (53%) were women, the median (interquartile range) age was 54 (48-60) years, and the median (interquartile range) peak V̇o2 level was 22.2 (17.85-27.35) mL/kg/min. IW was higher in patients with HFpEF and accounted for 27% (interquartile range, 21%-39%) of the total work (IW + measured external workload on the cycle), compared with 15% (interquartile range, 12%-20%) of that in FHS participants. Body mass index accounted for greatest explained variance in patients with HFpEF from MGH-ExS and FHS participants (22% and 18%, respectively), while resting cardiac output and biventricular filling pressures were not significantly associated with variance in IW in patients with HFpEF. A higher IW in patients with HFpEF was associated with a greater increase in left- and right-sided cardiac filing pressure during unloaded exercise, despite similar resting hemodynamic measures across IW.
This study found that internal work, a new body mass index-related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is associated with steep, early increases in cardiac filling pressures. These findings highlight the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.
We measured wavelength‐resolved ultraviolet (UV) irradiance in multiple indoor environments and quantified the effects of variables such as light source, solar angles, cloud cover, window type, and ...electric light color temperature on indoor photon fluxes. The majority of the 77 windows and window samples investigated completely attenuated sunlight at wavelengths shorter than 320 nm; despite variations among individual windows leading to differences in indoor HONO photolysis rate constants (JHONO) and local hydroxyl radical (OH) concentrations of up to a factor of 50, wavelength‐resolved transmittance was similar between windows in residential and non‐residential buildings. We report mathematical relationships that predict indoor solar UV irradiance as a function of solar zenith angle, incident angle of sunlight on windows, and distance from windows and surfaces for direct and diffuse sunlight. Using these relationships, we predict elevated indoor steady‐state OH concentrations (0.80–7.4 × 106 molec cm−3) under illumination by direct and diffuse sunlight and fluorescent tubes near windows or light sources. However, elevated OH concentrations at 1 m from the source are only predicted under direct sunlight. We predict that reflections from indoor surfaces will have minor contributions to room‐averaged indoor UV irradiance. These results may improve parameterization of indoor chemistry models.
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